BACKGROUND Pancreatic ductal adenocarcinoma(PDAC)is a highly fatal disease with limited effective treatment especially after first-line chemotherapy.The human epidermal growth factor receptor 2(HER-2)immunohistochemis...BACKGROUND Pancreatic ductal adenocarcinoma(PDAC)is a highly fatal disease with limited effective treatment especially after first-line chemotherapy.The human epidermal growth factor receptor 2(HER-2)immunohistochemistry(IHC)positive is associated with more aggressive clinical behavior and shorter overall survival in PDAC.CASE SUMMARY We present a case of multiple metastatic PDAC with IHC mismatch repair proficient but HER-2 IHC weakly positive at diagnosis that didn’t have tumor regression after first-line nab-paclitaxel plus gemcitabine and PD-1 inhibitor treatment.A novel combination therapy PRaG 3.0 of RC48(HER2-antibody-drug conjugate),radio-therapy,PD-1 inhibitor,granulocyte-macrophage colony-stimulating factor and interleukin-2 was then applied as second-line therapy and the patient had confirmed good partial response with progress-free-survival of 6.5 months and overall survival of 14.2 month.She had not developed any grade 2 or above treatment-related adverse events at any point.Percentage of peripheral CD8^(+) Temra and CD4^(+) Temra were increased during first two activation cycles of PRaG 3.0 treatment containing radiotherapy but deceased to the baseline during the maintenance cycles containing no radiotherapy.CONCLUSION PRaG 3.0 might be a novel strategy for HER2-positive metastatic PDAC patients who failed from previous first-line approach and even PD-1 immunotherapy but needs more data in prospective trials.展开更多
BACKGROUND Human epidermal growth factor receptor-2(HER-2)plays a vital role in tumor cell proliferation and metastasis.However,the prognosis of HER2-positive gastric cancer is poor.Inetetamab,a novel anti-HER2 target...BACKGROUND Human epidermal growth factor receptor-2(HER-2)plays a vital role in tumor cell proliferation and metastasis.However,the prognosis of HER2-positive gastric cancer is poor.Inetetamab,a novel anti-HER2 targeting drug independently developed in China,exhibits more potent antibody-dependent cell-mediated cytotoxicity than trastuzumab,which is administered as the first-line treatment for HER2-positive gastric cancer in combination with chemotherapy.In this case,the efficacy and safety of inetetamab combined with tegafur was investigated as a second-line treatment for HER2-positive gastric cancer.CASE SUMMARY A 52-year-old male patient with HER2-positive gastric cancer presented with abdominal distension,poor appetite,and fatigue two years after receiving six cycles of oxaliplatin combined with tegafur as first-line treatment after surgery,followed by tegafur monotherapy for six months.The patient was diagnosed with postoperative recurrence of gastric adenocarcinoma.He received 17 cycles of a combination of inetetamab,an innovative domestically developed anti-HER2 monoclonal antibody,and tegafur chemotherapy as the second-line treatment(inetetamab 200 mg on day 1,every 3 wk combined with tegafur twice daily on days 1–14,every 3 wk).Evaluation of the efficacy of the second-line treatment revealed that the patient achieved a stable condition and progression-free survival of 17 months.He tolerated the treatment well without exhibiting any grade 3-4 adverse events.CONCLUSION Inetetamab combined with chemotherapy for the treatment of metastatic HER2-positive gastric cancer demonstrates significant survival benefits and acceptable safety.展开更多
The body of evidence investigating human epidermal growth factor receptor-2(HER2)directed therapy in patients with breast cancer(BC)has been growing within the last decade.Recently,the use of tyrosine kinase inhibitor...The body of evidence investigating human epidermal growth factor receptor-2(HER2)directed therapy in patients with breast cancer(BC)has been growing within the last decade.Recently,the use of tyrosine kinase inhibitors(TKIs)has been of particular interest in the treatment of human malignancies.This literature commentary is intended to highlight the most recent findings associated with the widely-studied TKI agents and their clinical significance in improving the outcomes of HER2 positive BC.展开更多
Numerous molecular mechanisms are being examined in an attempt to discover disease-modifying drugs to slow down the underlying neurodegeneration in Alzheimer’s disease.Recent studies have shown the beneficial effects...Numerous molecular mechanisms are being examined in an attempt to discover disease-modifying drugs to slow down the underlying neurodegeneration in Alzheimer’s disease.Recent studies have shown the beneficial effects of epidermal growth factor receptor inhibitors on the enhancement of behavioral and pathological sequelae in Alzheimer’s disease.Despite the promising effects of epidermal growth factor receptor inhibitors in Alzheimer’s disease,there is no irrefutable neuroprotective evidence in well-established animal models using epidermal growth factor receptor inhibitors due to many un-explored downstream signaling pathways.This caused controversy about the potential involvement of epidermal growth factor receptor inhibitors in any prospective clinical trial.In this review,the mystery beyond the under-investigation of epidermal growth factor receptor in Alzheimer’s disease will be discussed.Furthermore,their molecular mechanisms in neurodegeneration will be explained.Also,we will shed light on SARS-COVID-19 induced neurological manifestations mediated by epidermal growth factor modulation.Finally,we will discuss future perspectives and under-examined epidermal growth factor receptor downstream signaling pathways that warrant more exploration.We conclude that epidermal growth factor receptor inhibitors are novel effective therapeutic approaches that require further research in attempts to be repositioned in the delay of Alzheimer’s disease progression.展开更多
Patients with early-stage non-small-cell lung cancer(NSCLC)are candidates for curative surgery;however,despite multiple advances in lung cancer management,recurrence rates remain high.Adjuvant chemotherapy has been de...Patients with early-stage non-small-cell lung cancer(NSCLC)are candidates for curative surgery;however,despite multiple advances in lung cancer management,recurrence rates remain high.Adjuvant chemotherapy has been demonstrated to significantly prolong overall survival(OS),but this benefit is modest and there is an urgent need for effective new therapies to provide a cure for more patients.The high efficacy of tyrosine kinase inhibitors(TKIs)against epidermal growth factor receptor-mutated(EGFR)in patients with advanced EGFR-mutated NSCLC has led to the evaluation of these agents in early stages of the disease.Multiple clinical trials have evaluated the safety and efficacy of EGFR TKIs as an adjuvant treatment,in patients with resected EGFR-mutated NSCLC,and shown that they significantly prolong disease-free survival(DFS),but this benefit does not translate to OS.Recently,an interim analysis of the ADAURA trial demonstrated that,surprisingly,osimertinib improved DFS.This led to the study being stopped early,leaving many unanswered questions about its potential effect on OS and its incorporation as a standard adjuvant treatment in this patient subgroup.These targeted agents are also being evaluated in locally-advanced disease,with promising results,although prospective studies with larger sample sizes are needed to confirm these results.In this article,we review the most relevant studies on the role of EGFR TKIs in the management of early-stage EGFR-mutated NSCLC.展开更多
Objective:To evaluate the human epidermal growth factor receptor 2(HER2)status in patients with breast cancer using multidetector computed tomography(MDCT)-based handcrafted and deep radiomics features.Methods:This re...Objective:To evaluate the human epidermal growth factor receptor 2(HER2)status in patients with breast cancer using multidetector computed tomography(MDCT)-based handcrafted and deep radiomics features.Methods:This retrospective study enrolled 339 female patients(primary cohort,n=177;validation cohort,n=162)with pathologically confirmed invasive breast cancer.Handcrafted and deep radiomics features were extracted from the MDCT images during the arterial phase.After the feature selection procedures,handcrafted and deep radiomics signatures and the combined model were built using multivariate logistic regression analysis.Performance was assessed by measures of discrimination,calibration,and clinical usefulness in the primary cohort and validated in the validation cohort.Results:The handcrafted radiomics signature had a discriminative ability with a C-index of 0.739[95%confidence interval(95%CI):0.661-0.818]in the primary cohort and 0.695(95%CI:0.609-0.781)in the validation cohort.The deep radiomics signature also had a discriminative ability with a C-index of 0.760(95%CI:0.690-0.831)in the primary cohort and 0.777(95%CI:0.696-0.857)in the validation cohort.The combined model,which incorporated both the handcrafted and deep radiomics signatures,showed good discriminative ability with a C-index of 0.829(95%CI:0.767-0.890)in the primary cohort and 0.809(95%CI:0.740-0.879)in the validation cohort.Conclusions:Handcrafted and deep radiomics features from MDCT images were associated with HER2 status in patients with breast cancer.Thus,these features could provide complementary aid for the radiological evaluation of HER2 status in breast cancer.展开更多
OBJECTIVE To investigate the role of connexin proteins(Cx),which form gap junctions(GJ),in progression and chemotherapeutic sensitivity of cervical cancer(CaC x).METHODS We analyze the expression of Cx26,Cx30,Cx32 and...OBJECTIVE To investigate the role of connexin proteins(Cx),which form gap junctions(GJ),in progression and chemotherapeutic sensitivity of cervical cancer(CaC x).METHODS We analyze the expression of Cx26,Cx30,Cx32 and Cx43 in human specimens consisting of:Normal cervix(n=78),CaCx FIGO stageⅠ(n=148),CaCx FIGO stageⅡ(n=165).In CaCx cell lines,Hela-Cx32(induced expression by doxycycline),C-33A(endogenously express Cx32)and si Ha(transiently transfected plasmid with Cx32),we detected the role of Cx32 against tostreptonigrin/cisplatin-induced apopotosisin presence or absence of functional GJ through using GJ inhibitors or low density cultural.Furtherly,we observed the relativity of Cx32 and EGFR expression in human specimens.Also,we detected the role of EGFR signaling pathway in the process of Cx32 anti-apoptosis through suppressed EGFR expression by inhibitors or si RNA sequences in cell lines.RESULTS We firstly demonstrated the expression of Cx32 was highly upregulated and accumulated in cytoplasm in the CaCx specimens,and the degree of upregulation correlated with advanced FIGO stages.Thus,in three human cervical cell lines,Cx32 was shown to suppress apoptosis when GJ formation is inhibited.No matter in cases of CaCx or cell lines,Cx32 expression was highly correlated with expression of EGFR and the EGFR pathway is an essential component of the Cx32-induced anti-apoptotic effect.CONCLUSION Cx32,traditionally tumor suppressive protein,was shown to be tumor protective against chemotherapy through EGFR pathway in a GJ-independent way.展开更多
BACKGROUND Icotinib could have potential effect and tolerability when used sequentially with chemotherapy for advanced epidermal growth factor receptor(EGFR)-mutated non-small cell lung cancer(NSCLC).AIM To evaluate t...BACKGROUND Icotinib could have potential effect and tolerability when used sequentially with chemotherapy for advanced epidermal growth factor receptor(EGFR)-mutated non-small cell lung cancer(NSCLC).AIM To evaluate the efficacy and safety of chemotherapy followed by icotinib maintenance therapy as first-line treatment for advanced EGFR-mutated NSCLC.METHODS This multicenter,open-label,pilot randomized controlled trial enrolled 68 EGFRmutated stage IIIB/IV NSCLC patients randomized 2:3 to the icotinib alone and chemotherapy+icotinib groups.RESULTS The median progression-free survival in the icotinib alone and chemotherapy+icotinib groups was 8.0 mo(95%CI:3.84-11.63)and 13.4 mo(95%CI:10.18-16.33),respectively(P=0.0249).No significant differences were found in the curative effect when considering different cycles of chemotherapy or chemotherapy regimen(all P>0.05).CONCLUSION A sequential combination of chemotherapy and EGFR-tyrosine kinase inhibitor is feasible for stage IV EGFR-mutated NSCLC patients.展开更多
BACKGROUND For lung adenocarcinoma with epidermal growth factor receptor(EGFR)gene mutation,small molecule tyrosine kinase inhibitors are more effective.Some patients could not obtain enough histological specimens for...BACKGROUND For lung adenocarcinoma with epidermal growth factor receptor(EGFR)gene mutation,small molecule tyrosine kinase inhibitors are more effective.Some patients could not obtain enough histological specimens for EGFR gene mutation detection.Specific imaging features can predict EGFR mutation status to a certain extent.AIM To assess the associations of EGFR mutations with high-resolution computerized tomography(HRCT)features in ground-glass nodular lung adenocarcinoma.METHODS This study retrospectively assessed patients with ground-glass nodular lung adenocarcinoma diagnosed between January 2011 and March 2017.EGFR gene mutations in exons 18-21 were detected.The patients were classified into mutant EGFR and wild-type groups,and general data and HRCT image characteristics were assessed.RESULTS Among 98 patients,31(31.6%)and 67(68.4%)had mutated and wild-type EGFR in exons 18-21,respectively.Gender,age,smoking history,location of lesions,morphology,edges,borders,pleural indentations,and associations of nodules with bronchus and blood vessels were comparable in both groups(all P>0.05).Patients with mutant EGFR had larger nodules than those with the wild-type(17.19±6.79 and 14.37±6.30 mm,respectively;P=0.047).Meanwhile,the vacuole/honeycomb sign was more frequent in the mutant EGFR group(P=0.011).The logistic regression prediction model included the combination of nodule size and vacuole/honeycomb sign(OR=1.120,95%CI:1.023-1.227,P=0.014)revealed a sensitivity of 83.9%,a specificity of 52.2%and an AUC of 0.698(95%CI:0.589-0.806;P=0.002).CONCLUSION Nodule size and vacuole/honeycomb features could independently predict EGFR mutation status in ground-glass nodular lung adenocarcinoma.展开更多
Endometrial cancer is the most common gynecological cancer in developed countries,and its incidence has increased.The majority of patients with endometrial cancer have an early disease and favorable prognosis;however,...Endometrial cancer is the most common gynecological cancer in developed countries,and its incidence has increased.The majority of patients with endometrial cancer have an early disease and favorable prognosis;however,a significant proportion of endometrial cancer,which mainly comprises high-grade or type II endometrial cancer such as serous,clear cell,and carcinosarcoma,shows advanced/recurrent disease and dismal prognosis.Novel therapeutic development is required for patients with aggressive endometrial cancers.Recent genomic and immunohistochemical analyses revealed human epidermal growth factor receptor 2(HER2)overexpression/gene amplification in 20%-40%of patients with type II endometrial cancer.Historically,HER2 targeted therapy has been developed for various major cancers,including breast and gastric cancer.Notably,recent advances in HER2 targeted therapy for patients with type II endometrial cancer are also expected to change.Simultaneously,an optimized HER2 test for endometrial cancer as companion diagnostics should be established.In this review,we summarize the recent findings on endometrial cancer,current treatment,optimized HER2 testing,key clinical trials on HER2 targeted therapy,and future directions in aggressive endometrial cancer,including serous carcinoma and carcinosarcoma.展开更多
Epidermal growth factor receptor(EGFR)signaling has become an importanttarget for drug development becauseEGFR signaling enhances tumor cell proliferation,migration,and invasion and inhibits apoptosis.However,theresul...Epidermal growth factor receptor(EGFR)signaling has become an importanttarget for drug development becauseEGFR signaling enhances tumor cell proliferation,migration,and invasion and inhibits apoptosis.However,theresults of clinical trials using EGFR inhibitors in patients with solid tumors have been disappointing.Here,wereport a protective effect of the EGFR inhibitors AG1478 and PD153035 against cell death induced by acute hy-poxia,which contrasts with their proapoptotic effects under normoxia.Under hypoxic conditions,both agents re-展开更多
BACKGROUND Colorectal cancer(CRC)is an extremely malignant tumor with a high mortality rate.Little is known about the mechanism by which forkhead Box q1(FOXQ1)causes CRC invasion and metastasis through the epidermal g...BACKGROUND Colorectal cancer(CRC)is an extremely malignant tumor with a high mortality rate.Little is known about the mechanism by which forkhead Box q1(FOXQ1)causes CRC invasion and metastasis through the epidermal growth factor receptor(EGFR)pathway.AIM To illuminate the mechanism by which FOXQ1 promotes the invasion and metastasis of CRC by activating the heparin binding epidermal growth factor(HB-EGF)/EGFR pathway.METHODS We investigated the differential expression and prognosis of FOXQ1 and HB-EGF in CRC using the Gene Expression Profiling Interactive Analysis(GEPIA)website(http://gepia.cancer-pku.cn/index.html).Quantitative real-time polymerase chain reaction(qRT-PCR)and Western blotting were used to detect the expression of FOXQ1 and HB-EGF in cell lines and tissues,and we constructed a stable lowexpressing FOXQ1 cell line and verified it with the above method.The expression changes of membrane-bound HB-EGF(proHB-EGF)and soluble HB-EGF(sHB-EGF)in the lowexpressing FOXQ1 cell line were detected by flow cytometry and ELISA.Western blotting was used to detect changes in the expression levels of HB-EGF and EGFR pathway-related downstream genes when exogenous recombinant human HB-EGF was added to FOXQ1 knockdown cells.Proliferation experiments,transwell migration experiments,and scratch experiments were carried out to determine the mechanism by which FOXQ1 activates the EGFR signaling pathway through HB-EGF,and then to evaluate the clinical relevance of FOXQ1 and HB-EGF.RESULTS GEPIA showed that the expression of FOXQ1 in CRC tissues was relatively high and was related to a lower overall survival rate.PCR array results showed that FOXQ1 is related to the HB-EGF and EGFR pathways.Knockdown of FOXQ1 suppressed the expression of HB-EGF,and led to a decrease in EGFR and its downstream genes AKT,RAF,KRAS expression levels.After knockdown of FOXQ1 in CRC cell lines,cell proliferation,migration and invasion were attenuated.Adding HB-EGF restored the migration and invasion ability of CRC,but not the cell proliferation ability.Kaplan–Meier survival analysis results showed that the combination of FOXQ1 and HB-EGF may serve to predict CRC survival.CONCLUSION Based on these collective data,we propose that FOXQ1 promotes the invasion and metastasis of CRC via the HB-EGF/EGFR pathway.展开更多
BACKGROUND Human epidermal growth factor receptor 2(HER2)amplification is a molecular driver for a subset of colorectal cancers(CRCs)and one of the major causes of anti-epidermal growth factor receptor(EGFR)treatment ...BACKGROUND Human epidermal growth factor receptor 2(HER2)amplification is a molecular driver for a subset of colorectal cancers(CRCs)and one of the major causes of anti-epidermal growth factor receptor(EGFR)treatment failure.Compared to dual anti-HER2 treatments,which have been shown to be effective in HER2-positive metastatic CRC patients,single-agent anti-HER2 therapy is rarely used to treat CRC.CASE SUMMARY Herein,we report a case of RAS/BRAF-wild-type metastatic CRC that was identified as HER2-positive through circulating tumor DNA(ctDNA)testing by next-generation sequencing following the failure of two lines of therapy.Subsequently,the patient was given lapatinib monotherapy that led to a partial response with a progression-free survival of 7.9 mo.Moreover,serial ctDNA detection was used to monitor the efficacy of lapatinib.The aberration of HER2 copy number disappeared when radiographic assessment revealed a partial response.However,a high level of HER2 amplification was detected again at the time of disease progression.Finally,a phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha mutation was identified at the time of tumor progression,which may explain the acquired resistance to lapatinib.CONCLUSION This is the first case report of HER2-positive RAS/BRAF wild-type metastatic CRC patient responding to lapatinib monotherapy.It highlights that ctDNA testing is an effective and feasible approach to evaluate the efficacy of anti-HER2 therapy.展开更多
BACKGROUND Epidermal growth factor receptor(EGFR)tyrosine kinase inhibitors(TKIs)have been adopted as the standard of care for non-small cell lung cancer(NSCLC)patients harboring EGFR sensitizing mutations.Besides the...BACKGROUND Epidermal growth factor receptor(EGFR)tyrosine kinase inhibitors(TKIs)have been adopted as the standard of care for non-small cell lung cancer(NSCLC)patients harboring EGFR sensitizing mutations.Besides the two common mutations exon 19 deletion and L858R,which together comprise approximately 85%of EGFR mutations in NSCLC,rare EGFR mutations also exist,including point mutations,deletions,and insertions spanning EGFR exons 18-25.However,the responsiveness of uncommon EGFR mutations to EGFR TKIs remains elusive and attracts increasing interest.CASE SUMMARY Herein,we report a 55-year-old male patient with stage IV NSCLC harboring a rare EGFR L833F-L861Q compound mutation in cis.The patient achieved a partial response to first-line treatment with afatinib and a progression-free survival of 10 mo.After afatinib failure,the patient received multiple line treatments with chemotherapy.Upon disease progression,the heavily pretreated patient was treated with osimertinib and bevacizumab,and both lung lesion and brain metastases were stable for more than 3 mo.He had an overall survival of 25 mo.CONCLUSION Our case revealed that both afatinib and the osimertinib+bevacizumab combination demonstrated clinical efficacy in NSCLC harboring an EGFR L833FL861Q compound mutation.The results provide more therapeutic options for patients with rare compound mutations.展开更多
BACKGROUND The advent of immune checkpoint inhibitors(ICIs)has revolutionized the management of several types of solid cancers,including lung cancer,by boosting the body's natural tumor killing response.However,it...BACKGROUND The advent of immune checkpoint inhibitors(ICIs)has revolutionized the management of several types of solid cancers,including lung cancer,by boosting the body's natural tumor killing response.However,it is undeniable that only a small proportion of non-small cell lung cancer(NSCLC)patients with epidermal growth factor receptor(EGFR)mutations can achieve long-term responses and benefit from immunotherapy.CASE SUMMARY Herein,we report the case of a 48-year-old man diagnosed with stage IV lung adenocarcinoma with an EGFR L858R mutation who was administered pembrolizumab monotherapy followed by pemetrexed and achieved a 10-month progression-free survival interval.In this case report,we show that ICIs were effective for our patient with EGFR-mutated NSCLC and discuss the characteristics of patients who can benefit from immunotherapy.CONCLUSION We suggest that patients with EGFR-mutated NSCLC with high PD-L1 expression(defined as≥25%),the L858R mutation,smoking history,or pemetrexed pretreatment may benefit from immunotherapy.展开更多
BACKGROUND Accumulating evidences confirm that epidermal growth factor receptor(EGFR)mutation and anaplastic lymphoma kinase(ALK)rearrangement have coexisted in lung adenocarcinoma(LUAD).However,Its biological mechani...BACKGROUND Accumulating evidences confirm that epidermal growth factor receptor(EGFR)mutation and anaplastic lymphoma kinase(ALK)rearrangement have coexisted in lung adenocarcinoma(LUAD).However,Its biological mechanism,clinicopathological features,and optimization of targeted drugs have not yet been completely elucidated.AIM To explore the clinical profile of LUAD patients with co-mutations of EGFR and ALK genes,with hopes of scientifically guiding similar patients towards selected,targeted drugs.METHODS Two hundred and thirty-seven LUAD patients were enrolled.EGFR mutations were detected by the amplification refractory mutation system-peptide nucleic acid technique,while the expression of ALK rearrangement was screened by the 5′/3′imbalance strategy for reverse transcription followed by quantitative polymerase chain reaction analysis.The clinicopathological features of these patients were analysed retrospectively,and the follow-up data were collected.RESULTS There were six cases with co-mutations of EGFR and ALK genes,which were more common in women,non-smoking and stage IV LUAD patients with bone metastasis,hence a positive rate of 2.53%(6/237).EGFR-tyrosine kinase inhibitors(EGFR-TKIs)were their preferred drugs for targeted therapy in these patients,with progression-free survival ranging from two months to six months.CONCLUSION In Gannan region,the positive rate of co-mutations of EGFR and ALK genes in LUAD patients is relatively high,and the co-mutations are more common in women,non-smoking and stage IV patients with bone metastasis.These patients prefer EGFR-TKIs as their preferred targeted drugs,but the therapeutic effect is not good.EGFR/ALK dual-TKIs may be more effective targeted drugs,which needs further study.展开更多
BACKGROUND Invasive lobular carcinomas(ILC)form 5%-10%of breast cancer and rarely show overexpression of human epidermal growth factor receptor 2(HER2).AIM To describe the prevalence and prognostic factors of HER2 pos...BACKGROUND Invasive lobular carcinomas(ILC)form 5%-10%of breast cancer and rarely show overexpression of human epidermal growth factor receptor 2(HER2).AIM To describe the prevalence and prognostic factors of HER2 positive(HER2+)ILC in an Asian population.METHODS A retrospective review of patients with ILC seen between January 1985 and March 2018 at various SingHealth medical institutions was conducted.Demographic and clinical data were collected from medical records.We examined clinicopathological characteristics and survival in relation to HER2 status.RESULTS A total of 864 patients were included.Prevalence of HER2 positivity was 10.1%(87 patients).Compared with HER2 negative(HER2-)ILC,HER2+ILC was associated with a higher proportion of estrogen receptor negative(24.4%vs 5.9%,P<0.001),progesterone receptor negative(PR-)(40.2%vs 24%,P=0.002)and grade 3 tumours(Grade 3,29.0%vs 10.2%,P<0.001).Overall survival rate was poorer in patients with HER2+compared to HER2-ILC(56.7%vs 72.9%alive at 10 years;hazard ratio 1.87,95%confidence interval:1.21-2.90,P=0.004).Based on multivariate analysis,negative prognostic factors for overall survival included HER2 positivity,PR negativity,older age,Indian ethnicity and higher tumour stage.CONCLUSION Prevalence of HER2+ILC was 10.1%.HER2+ILC was more likely to have poorer prognostic features such as estrogen receptor negative,PR-and higher tumour grade,and have a poorer survival.展开更多
BACKGROUND Epidermal growth factor receptor(EGFR)tyrosine-kinase inhibitors are widely used for the treatment of non-small-cell lung cancer with EGFR mutations.However,patients with rare,even compound EGFR mutations h...BACKGROUND Epidermal growth factor receptor(EGFR)tyrosine-kinase inhibitors are widely used for the treatment of non-small-cell lung cancer with EGFR mutations.However,patients with rare,even compound EGFR mutations have different responses to EGFR-tyrosine-kinase inhibitors,which bring uncertainty to clinical treatment.CASE SUMMARY A 45-year-old female patient presented with a 3-mo history of cough and white sputum without chest pain.Chest computed tomography revealed lung spaceoccupying lesions and multiple lymphadenectasis.Bronchoscopy and pathology suggested lung adenocarcinoma.Compound variation of EGFR gene(exon 21 L858 R/V834 L)was detected in both tissue and circulating tumor deoxyribonucleic acid samples.As a result of next-generation sequencing and her family’s wishes,the patient was given oral treatment with icotinib hydrochloride(125 mg/d,tid)from March 21,2019 and has achieved stable disease for the last 1 year.CONCLUSION Non-small cell lung adenocarcinoma with EGFR L858 R/V834 L was treated successfully with icotinib,and it may be a new medication treatment option.展开更多
Non-small-cell lung cancer(NSCLC)causes significant mortality worldwide.Patients with chronic renal failure have an increased risk of developing lungcancer.NSCLC Patients with chronic renal failure undergoing hemodial...Non-small-cell lung cancer(NSCLC)causes significant mortality worldwide.Patients with chronic renal failure have an increased risk of developing lungcancer.NSCLC Patients with chronic renal failure undergoing hemodialysis(HD)often exhibit poor performance,and chemotherapy is generally contraindicated.Oral epidermal growth factor receptor(EGFR)-tyrosine kinase inhibitors(TKIs)are effective treatment agents for NSCLC patients.However,the benefits andadverse effects of EGFR-TKIs in NSCLC undergoing HD are known.There are noclinical studies on the effects of EGFR-TKIs on NSCLC patients undergoing HD.We reviewed all previous case reports about EGFR-TKIs in NSCLC patientsundergoing HD.It is difficult to design studies about the effects of EGFR-TKIs inpatients undergoing HD,and this review is quite important.EGFR-TKIs are welltolerated in patients undergoing HD.The main routes of elimination of EGFRTKIsare metabolism via the liver,and renal elimination is minor.Therecommended doses and pharmacokinetics of these EGFR-TKIs for patientsundergoing HD are similar to those for patients with normal renal function.Theplasma protein binding of EGFR-TKIs is very high,and it is not necessary toadjust the dose after HD.In conclusion,EGFR-TKIs are effective and welltolerated in patients undergoing HD.展开更多
Objective:To verify the efficacy of the Chinese medicine“Zhiyang Pingfu Liquid”on the lesion associated with Epidermal Growth Factor Receptor Inhibitors(EGFRIs).Methods:Female BN rats were divided into Control group...Objective:To verify the efficacy of the Chinese medicine“Zhiyang Pingfu Liquid”on the lesion associated with Epidermal Growth Factor Receptor Inhibitors(EGFRIs).Methods:Female BN rats were divided into Control group and Gefitinib group randomly.The Gefitinib group was administered gefitinib for 21 days.After 21 days,the rats in the Gefitinib group were grouped again and randomly divided into Model group,Gefitinib+ZY group,and Gefitinib+NS group.Starting from day 22,rats in Gefitinib+ZY or NS were given different drugs for 7 days besides the other conditions are as the same as before.Observe the morphological changes and histopathological changes of the skin during the research.The changes of inflammatory factors such as TNF-αand IL-6 in the serum of were detected by ELISA.Results:The application of“Zhiyang Pingfu Liquid”for 7 days could significantly reduce the skin inflammation whether in gross or pathological view.The concentration of TNF-αand IL-6 in Gefitinib+ZY is significantly lower than those in the Model group(P=0.002,P=0.002)and there is no significant changes compared with the Control group(P=0.279,P=0.165).Conclusion:Chinese herbal“Zhiyang Pingfu Liquid”can reduce the lesion and inflammatory caused by EGFRIs.展开更多
基金the Suzhou Medical Center,No.Szlcyxzx202103the National Natural Science Foundation of China,No.82171828+9 种基金the Key R&D Plan of Jiangsu Province(Social Development),No.BE2021652the Subject Construction Support Project of The Second Affiliated Hospital of Soochow University,No.XKTJHRC20210011Wu Jieping Medical Foundation,No.320.6750.2021-01-12the Special Project of“Technological Innovation”Project of CNNC Medical Industry Co.Ltd,No.ZHYLTD2021001Suzhou Science and Education Health Project,No.KJXW2021018Foundation of Chinese Society of Clinical Oncology,No.Y-pierrefabre202102-0113Beijing Bethune Charitable Foundation,No.STLKY0016Research Projects of China Baoyuan Investment Co.,No.270004Suzhou Gusu Health Talent Program,No.GSWS2022028Open Project of State Key Laboratory of Radiation Medicine and Protection of Soochow University,No.GZN1202302.
文摘BACKGROUND Pancreatic ductal adenocarcinoma(PDAC)is a highly fatal disease with limited effective treatment especially after first-line chemotherapy.The human epidermal growth factor receptor 2(HER-2)immunohistochemistry(IHC)positive is associated with more aggressive clinical behavior and shorter overall survival in PDAC.CASE SUMMARY We present a case of multiple metastatic PDAC with IHC mismatch repair proficient but HER-2 IHC weakly positive at diagnosis that didn’t have tumor regression after first-line nab-paclitaxel plus gemcitabine and PD-1 inhibitor treatment.A novel combination therapy PRaG 3.0 of RC48(HER2-antibody-drug conjugate),radio-therapy,PD-1 inhibitor,granulocyte-macrophage colony-stimulating factor and interleukin-2 was then applied as second-line therapy and the patient had confirmed good partial response with progress-free-survival of 6.5 months and overall survival of 14.2 month.She had not developed any grade 2 or above treatment-related adverse events at any point.Percentage of peripheral CD8^(+) Temra and CD4^(+) Temra were increased during first two activation cycles of PRaG 3.0 treatment containing radiotherapy but deceased to the baseline during the maintenance cycles containing no radiotherapy.CONCLUSION PRaG 3.0 might be a novel strategy for HER2-positive metastatic PDAC patients who failed from previous first-line approach and even PD-1 immunotherapy but needs more data in prospective trials.
基金Supported by the Science and Technology Innovation Development Project of Tai’an,No.2021NS160the Medical and Health Science and Technology Development Plan of Shandong Province,No.202102010647。
文摘BACKGROUND Human epidermal growth factor receptor-2(HER-2)plays a vital role in tumor cell proliferation and metastasis.However,the prognosis of HER2-positive gastric cancer is poor.Inetetamab,a novel anti-HER2 targeting drug independently developed in China,exhibits more potent antibody-dependent cell-mediated cytotoxicity than trastuzumab,which is administered as the first-line treatment for HER2-positive gastric cancer in combination with chemotherapy.In this case,the efficacy and safety of inetetamab combined with tegafur was investigated as a second-line treatment for HER2-positive gastric cancer.CASE SUMMARY A 52-year-old male patient with HER2-positive gastric cancer presented with abdominal distension,poor appetite,and fatigue two years after receiving six cycles of oxaliplatin combined with tegafur as first-line treatment after surgery,followed by tegafur monotherapy for six months.The patient was diagnosed with postoperative recurrence of gastric adenocarcinoma.He received 17 cycles of a combination of inetetamab,an innovative domestically developed anti-HER2 monoclonal antibody,and tegafur chemotherapy as the second-line treatment(inetetamab 200 mg on day 1,every 3 wk combined with tegafur twice daily on days 1–14,every 3 wk).Evaluation of the efficacy of the second-line treatment revealed that the patient achieved a stable condition and progression-free survival of 17 months.He tolerated the treatment well without exhibiting any grade 3-4 adverse events.CONCLUSION Inetetamab combined with chemotherapy for the treatment of metastatic HER2-positive gastric cancer demonstrates significant survival benefits and acceptable safety.
基金Supported by the Elsa U.Pardee Foundation Grant,No.671432(to Sahu RP)NIH R21 Grant,No.ES033806(to Sahu RP).
文摘The body of evidence investigating human epidermal growth factor receptor-2(HER2)directed therapy in patients with breast cancer(BC)has been growing within the last decade.Recently,the use of tyrosine kinase inhibitors(TKIs)has been of particular interest in the treatment of human malignancies.This literature commentary is intended to highlight the most recent findings associated with the widely-studied TKI agents and their clinical significance in improving the outcomes of HER2 positive BC.
文摘Numerous molecular mechanisms are being examined in an attempt to discover disease-modifying drugs to slow down the underlying neurodegeneration in Alzheimer’s disease.Recent studies have shown the beneficial effects of epidermal growth factor receptor inhibitors on the enhancement of behavioral and pathological sequelae in Alzheimer’s disease.Despite the promising effects of epidermal growth factor receptor inhibitors in Alzheimer’s disease,there is no irrefutable neuroprotective evidence in well-established animal models using epidermal growth factor receptor inhibitors due to many un-explored downstream signaling pathways.This caused controversy about the potential involvement of epidermal growth factor receptor inhibitors in any prospective clinical trial.In this review,the mystery beyond the under-investigation of epidermal growth factor receptor in Alzheimer’s disease will be discussed.Furthermore,their molecular mechanisms in neurodegeneration will be explained.Also,we will shed light on SARS-COVID-19 induced neurological manifestations mediated by epidermal growth factor modulation.Finally,we will discuss future perspectives and under-examined epidermal growth factor receptor downstream signaling pathways that warrant more exploration.We conclude that epidermal growth factor receptor inhibitors are novel effective therapeutic approaches that require further research in attempts to be repositioned in the delay of Alzheimer’s disease progression.
文摘Patients with early-stage non-small-cell lung cancer(NSCLC)are candidates for curative surgery;however,despite multiple advances in lung cancer management,recurrence rates remain high.Adjuvant chemotherapy has been demonstrated to significantly prolong overall survival(OS),but this benefit is modest and there is an urgent need for effective new therapies to provide a cure for more patients.The high efficacy of tyrosine kinase inhibitors(TKIs)against epidermal growth factor receptor-mutated(EGFR)in patients with advanced EGFR-mutated NSCLC has led to the evaluation of these agents in early stages of the disease.Multiple clinical trials have evaluated the safety and efficacy of EGFR TKIs as an adjuvant treatment,in patients with resected EGFR-mutated NSCLC,and shown that they significantly prolong disease-free survival(DFS),but this benefit does not translate to OS.Recently,an interim analysis of the ADAURA trial demonstrated that,surprisingly,osimertinib improved DFS.This led to the study being stopped early,leaving many unanswered questions about its potential effect on OS and its incorporation as a standard adjuvant treatment in this patient subgroup.These targeted agents are also being evaluated in locally-advanced disease,with promising results,although prospective studies with larger sample sizes are needed to confirm these results.In this article,we review the most relevant studies on the role of EGFR TKIs in the management of early-stage EGFR-mutated NSCLC.
基金supported by the National Key R&D Program of China(No.2017YFC1309100)the National Science Fund for Distinguished Young Scholars(No.81925023)+1 种基金the National Natural Science Foundation of China(No.81771912,81701662,81701782,81601469,and 81702322)Science and Technology Planning Project of Guangdong Province(No.2017B020227012)。
文摘Objective:To evaluate the human epidermal growth factor receptor 2(HER2)status in patients with breast cancer using multidetector computed tomography(MDCT)-based handcrafted and deep radiomics features.Methods:This retrospective study enrolled 339 female patients(primary cohort,n=177;validation cohort,n=162)with pathologically confirmed invasive breast cancer.Handcrafted and deep radiomics features were extracted from the MDCT images during the arterial phase.After the feature selection procedures,handcrafted and deep radiomics signatures and the combined model were built using multivariate logistic regression analysis.Performance was assessed by measures of discrimination,calibration,and clinical usefulness in the primary cohort and validated in the validation cohort.Results:The handcrafted radiomics signature had a discriminative ability with a C-index of 0.739[95%confidence interval(95%CI):0.661-0.818]in the primary cohort and 0.695(95%CI:0.609-0.781)in the validation cohort.The deep radiomics signature also had a discriminative ability with a C-index of 0.760(95%CI:0.690-0.831)in the primary cohort and 0.777(95%CI:0.696-0.857)in the validation cohort.The combined model,which incorporated both the handcrafted and deep radiomics signatures,showed good discriminative ability with a C-index of 0.829(95%CI:0.767-0.890)in the primary cohort and 0.809(95%CI:0.740-0.879)in the validation cohort.Conclusions:Handcrafted and deep radiomics features from MDCT images were associated with HER2 status in patients with breast cancer.Thus,these features could provide complementary aid for the radiological evaluation of HER2 status in breast cancer.
基金supported by National Nature Science Foundation of China(U1303221)National Natural Science Foundation of China(81373439,81473234)Construction of Technique Plate for Evaluation of the Pharmacodynamics of New Drugs in Xinjiang from the Department of Science and Technology of Xinjiang Province(201233150)
文摘OBJECTIVE To investigate the role of connexin proteins(Cx),which form gap junctions(GJ),in progression and chemotherapeutic sensitivity of cervical cancer(CaC x).METHODS We analyze the expression of Cx26,Cx30,Cx32 and Cx43 in human specimens consisting of:Normal cervix(n=78),CaCx FIGO stageⅠ(n=148),CaCx FIGO stageⅡ(n=165).In CaCx cell lines,Hela-Cx32(induced expression by doxycycline),C-33A(endogenously express Cx32)and si Ha(transiently transfected plasmid with Cx32),we detected the role of Cx32 against tostreptonigrin/cisplatin-induced apopotosisin presence or absence of functional GJ through using GJ inhibitors or low density cultural.Furtherly,we observed the relativity of Cx32 and EGFR expression in human specimens.Also,we detected the role of EGFR signaling pathway in the process of Cx32 anti-apoptosis through suppressed EGFR expression by inhibitors or si RNA sequences in cell lines.RESULTS We firstly demonstrated the expression of Cx32 was highly upregulated and accumulated in cytoplasm in the CaCx specimens,and the degree of upregulation correlated with advanced FIGO stages.Thus,in three human cervical cell lines,Cx32 was shown to suppress apoptosis when GJ formation is inhibited.No matter in cases of CaCx or cell lines,Cx32 expression was highly correlated with expression of EGFR and the EGFR pathway is an essential component of the Cx32-induced anti-apoptotic effect.CONCLUSION Cx32,traditionally tumor suppressive protein,was shown to be tumor protective against chemotherapy through EGFR pathway in a GJ-independent way.
文摘BACKGROUND Icotinib could have potential effect and tolerability when used sequentially with chemotherapy for advanced epidermal growth factor receptor(EGFR)-mutated non-small cell lung cancer(NSCLC).AIM To evaluate the efficacy and safety of chemotherapy followed by icotinib maintenance therapy as first-line treatment for advanced EGFR-mutated NSCLC.METHODS This multicenter,open-label,pilot randomized controlled trial enrolled 68 EGFRmutated stage IIIB/IV NSCLC patients randomized 2:3 to the icotinib alone and chemotherapy+icotinib groups.RESULTS The median progression-free survival in the icotinib alone and chemotherapy+icotinib groups was 8.0 mo(95%CI:3.84-11.63)and 13.4 mo(95%CI:10.18-16.33),respectively(P=0.0249).No significant differences were found in the curative effect when considering different cycles of chemotherapy or chemotherapy regimen(all P>0.05).CONCLUSION A sequential combination of chemotherapy and EGFR-tyrosine kinase inhibitor is feasible for stage IV EGFR-mutated NSCLC patients.
基金by the Zhejiang Province Traditional Chinese Medicine Science and Technology Plan-Zhejiang Province Traditional Chinese Medicine Project for Traditional Chinese Medicine Scientific Research(2020)(Class B),No.2020ZB117。
文摘BACKGROUND For lung adenocarcinoma with epidermal growth factor receptor(EGFR)gene mutation,small molecule tyrosine kinase inhibitors are more effective.Some patients could not obtain enough histological specimens for EGFR gene mutation detection.Specific imaging features can predict EGFR mutation status to a certain extent.AIM To assess the associations of EGFR mutations with high-resolution computerized tomography(HRCT)features in ground-glass nodular lung adenocarcinoma.METHODS This study retrospectively assessed patients with ground-glass nodular lung adenocarcinoma diagnosed between January 2011 and March 2017.EGFR gene mutations in exons 18-21 were detected.The patients were classified into mutant EGFR and wild-type groups,and general data and HRCT image characteristics were assessed.RESULTS Among 98 patients,31(31.6%)and 67(68.4%)had mutated and wild-type EGFR in exons 18-21,respectively.Gender,age,smoking history,location of lesions,morphology,edges,borders,pleural indentations,and associations of nodules with bronchus and blood vessels were comparable in both groups(all P>0.05).Patients with mutant EGFR had larger nodules than those with the wild-type(17.19±6.79 and 14.37±6.30 mm,respectively;P=0.047).Meanwhile,the vacuole/honeycomb sign was more frequent in the mutant EGFR group(P=0.011).The logistic regression prediction model included the combination of nodule size and vacuole/honeycomb sign(OR=1.120,95%CI:1.023-1.227,P=0.014)revealed a sensitivity of 83.9%,a specificity of 52.2%and an AUC of 0.698(95%CI:0.589-0.806;P=0.002).CONCLUSION Nodule size and vacuole/honeycomb features could independently predict EGFR mutation status in ground-glass nodular lung adenocarcinoma.
文摘Endometrial cancer is the most common gynecological cancer in developed countries,and its incidence has increased.The majority of patients with endometrial cancer have an early disease and favorable prognosis;however,a significant proportion of endometrial cancer,which mainly comprises high-grade or type II endometrial cancer such as serous,clear cell,and carcinosarcoma,shows advanced/recurrent disease and dismal prognosis.Novel therapeutic development is required for patients with aggressive endometrial cancers.Recent genomic and immunohistochemical analyses revealed human epidermal growth factor receptor 2(HER2)overexpression/gene amplification in 20%-40%of patients with type II endometrial cancer.Historically,HER2 targeted therapy has been developed for various major cancers,including breast and gastric cancer.Notably,recent advances in HER2 targeted therapy for patients with type II endometrial cancer are also expected to change.Simultaneously,an optimized HER2 test for endometrial cancer as companion diagnostics should be established.In this review,we summarize the recent findings on endometrial cancer,current treatment,optimized HER2 testing,key clinical trials on HER2 targeted therapy,and future directions in aggressive endometrial cancer,including serous carcinoma and carcinosarcoma.
文摘Epidermal growth factor receptor(EGFR)signaling has become an importanttarget for drug development becauseEGFR signaling enhances tumor cell proliferation,migration,and invasion and inhibits apoptosis.However,theresults of clinical trials using EGFR inhibitors in patients with solid tumors have been disappointing.Here,wereport a protective effect of the EGFR inhibitors AG1478 and PD153035 against cell death induced by acute hy-poxia,which contrasts with their proapoptotic effects under normoxia.Under hypoxic conditions,both agents re-
基金Supported by National Natural Science Foundation of China,No. 81502556Yunnan Digestive Endoscopy Clinical Medical Center Foundation for Health Commission of Yunnan Province,No. 2X2019-01-02
文摘BACKGROUND Colorectal cancer(CRC)is an extremely malignant tumor with a high mortality rate.Little is known about the mechanism by which forkhead Box q1(FOXQ1)causes CRC invasion and metastasis through the epidermal growth factor receptor(EGFR)pathway.AIM To illuminate the mechanism by which FOXQ1 promotes the invasion and metastasis of CRC by activating the heparin binding epidermal growth factor(HB-EGF)/EGFR pathway.METHODS We investigated the differential expression and prognosis of FOXQ1 and HB-EGF in CRC using the Gene Expression Profiling Interactive Analysis(GEPIA)website(http://gepia.cancer-pku.cn/index.html).Quantitative real-time polymerase chain reaction(qRT-PCR)and Western blotting were used to detect the expression of FOXQ1 and HB-EGF in cell lines and tissues,and we constructed a stable lowexpressing FOXQ1 cell line and verified it with the above method.The expression changes of membrane-bound HB-EGF(proHB-EGF)and soluble HB-EGF(sHB-EGF)in the lowexpressing FOXQ1 cell line were detected by flow cytometry and ELISA.Western blotting was used to detect changes in the expression levels of HB-EGF and EGFR pathway-related downstream genes when exogenous recombinant human HB-EGF was added to FOXQ1 knockdown cells.Proliferation experiments,transwell migration experiments,and scratch experiments were carried out to determine the mechanism by which FOXQ1 activates the EGFR signaling pathway through HB-EGF,and then to evaluate the clinical relevance of FOXQ1 and HB-EGF.RESULTS GEPIA showed that the expression of FOXQ1 in CRC tissues was relatively high and was related to a lower overall survival rate.PCR array results showed that FOXQ1 is related to the HB-EGF and EGFR pathways.Knockdown of FOXQ1 suppressed the expression of HB-EGF,and led to a decrease in EGFR and its downstream genes AKT,RAF,KRAS expression levels.After knockdown of FOXQ1 in CRC cell lines,cell proliferation,migration and invasion were attenuated.Adding HB-EGF restored the migration and invasion ability of CRC,but not the cell proliferation ability.Kaplan–Meier survival analysis results showed that the combination of FOXQ1 and HB-EGF may serve to predict CRC survival.CONCLUSION Based on these collective data,we propose that FOXQ1 promotes the invasion and metastasis of CRC via the HB-EGF/EGFR pathway.
文摘BACKGROUND Human epidermal growth factor receptor 2(HER2)amplification is a molecular driver for a subset of colorectal cancers(CRCs)and one of the major causes of anti-epidermal growth factor receptor(EGFR)treatment failure.Compared to dual anti-HER2 treatments,which have been shown to be effective in HER2-positive metastatic CRC patients,single-agent anti-HER2 therapy is rarely used to treat CRC.CASE SUMMARY Herein,we report a case of RAS/BRAF-wild-type metastatic CRC that was identified as HER2-positive through circulating tumor DNA(ctDNA)testing by next-generation sequencing following the failure of two lines of therapy.Subsequently,the patient was given lapatinib monotherapy that led to a partial response with a progression-free survival of 7.9 mo.Moreover,serial ctDNA detection was used to monitor the efficacy of lapatinib.The aberration of HER2 copy number disappeared when radiographic assessment revealed a partial response.However,a high level of HER2 amplification was detected again at the time of disease progression.Finally,a phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha mutation was identified at the time of tumor progression,which may explain the acquired resistance to lapatinib.CONCLUSION This is the first case report of HER2-positive RAS/BRAF wild-type metastatic CRC patient responding to lapatinib monotherapy.It highlights that ctDNA testing is an effective and feasible approach to evaluate the efficacy of anti-HER2 therapy.
文摘BACKGROUND Epidermal growth factor receptor(EGFR)tyrosine kinase inhibitors(TKIs)have been adopted as the standard of care for non-small cell lung cancer(NSCLC)patients harboring EGFR sensitizing mutations.Besides the two common mutations exon 19 deletion and L858R,which together comprise approximately 85%of EGFR mutations in NSCLC,rare EGFR mutations also exist,including point mutations,deletions,and insertions spanning EGFR exons 18-25.However,the responsiveness of uncommon EGFR mutations to EGFR TKIs remains elusive and attracts increasing interest.CASE SUMMARY Herein,we report a 55-year-old male patient with stage IV NSCLC harboring a rare EGFR L833F-L861Q compound mutation in cis.The patient achieved a partial response to first-line treatment with afatinib and a progression-free survival of 10 mo.After afatinib failure,the patient received multiple line treatments with chemotherapy.Upon disease progression,the heavily pretreated patient was treated with osimertinib and bevacizumab,and both lung lesion and brain metastases were stable for more than 3 mo.He had an overall survival of 25 mo.CONCLUSION Our case revealed that both afatinib and the osimertinib+bevacizumab combination demonstrated clinical efficacy in NSCLC harboring an EGFR L833FL861Q compound mutation.The results provide more therapeutic options for patients with rare compound mutations.
基金Henan Provincial Science and Technology Research Project,No.202102310157Medical Science and Technology Research Plan(Joint Construction)Project of Henan Province,No.LHGJ20190676.
文摘BACKGROUND The advent of immune checkpoint inhibitors(ICIs)has revolutionized the management of several types of solid cancers,including lung cancer,by boosting the body's natural tumor killing response.However,it is undeniable that only a small proportion of non-small cell lung cancer(NSCLC)patients with epidermal growth factor receptor(EGFR)mutations can achieve long-term responses and benefit from immunotherapy.CASE SUMMARY Herein,we report the case of a 48-year-old man diagnosed with stage IV lung adenocarcinoma with an EGFR L858R mutation who was administered pembrolizumab monotherapy followed by pemetrexed and achieved a 10-month progression-free survival interval.In this case report,we show that ICIs were effective for our patient with EGFR-mutated NSCLC and discuss the characteristics of patients who can benefit from immunotherapy.CONCLUSION We suggest that patients with EGFR-mutated NSCLC with high PD-L1 expression(defined as≥25%),the L858R mutation,smoking history,or pemetrexed pretreatment may benefit from immunotherapy.
文摘BACKGROUND Accumulating evidences confirm that epidermal growth factor receptor(EGFR)mutation and anaplastic lymphoma kinase(ALK)rearrangement have coexisted in lung adenocarcinoma(LUAD).However,Its biological mechanism,clinicopathological features,and optimization of targeted drugs have not yet been completely elucidated.AIM To explore the clinical profile of LUAD patients with co-mutations of EGFR and ALK genes,with hopes of scientifically guiding similar patients towards selected,targeted drugs.METHODS Two hundred and thirty-seven LUAD patients were enrolled.EGFR mutations were detected by the amplification refractory mutation system-peptide nucleic acid technique,while the expression of ALK rearrangement was screened by the 5′/3′imbalance strategy for reverse transcription followed by quantitative polymerase chain reaction analysis.The clinicopathological features of these patients were analysed retrospectively,and the follow-up data were collected.RESULTS There were six cases with co-mutations of EGFR and ALK genes,which were more common in women,non-smoking and stage IV LUAD patients with bone metastasis,hence a positive rate of 2.53%(6/237).EGFR-tyrosine kinase inhibitors(EGFR-TKIs)were their preferred drugs for targeted therapy in these patients,with progression-free survival ranging from two months to six months.CONCLUSION In Gannan region,the positive rate of co-mutations of EGFR and ALK genes in LUAD patients is relatively high,and the co-mutations are more common in women,non-smoking and stage IV patients with bone metastasis.These patients prefer EGFR-TKIs as their preferred targeted drugs,but the therapeutic effect is not good.EGFR/ALK dual-TKIs may be more effective targeted drugs,which needs further study.
文摘BACKGROUND Invasive lobular carcinomas(ILC)form 5%-10%of breast cancer and rarely show overexpression of human epidermal growth factor receptor 2(HER2).AIM To describe the prevalence and prognostic factors of HER2 positive(HER2+)ILC in an Asian population.METHODS A retrospective review of patients with ILC seen between January 1985 and March 2018 at various SingHealth medical institutions was conducted.Demographic and clinical data were collected from medical records.We examined clinicopathological characteristics and survival in relation to HER2 status.RESULTS A total of 864 patients were included.Prevalence of HER2 positivity was 10.1%(87 patients).Compared with HER2 negative(HER2-)ILC,HER2+ILC was associated with a higher proportion of estrogen receptor negative(24.4%vs 5.9%,P<0.001),progesterone receptor negative(PR-)(40.2%vs 24%,P=0.002)and grade 3 tumours(Grade 3,29.0%vs 10.2%,P<0.001).Overall survival rate was poorer in patients with HER2+compared to HER2-ILC(56.7%vs 72.9%alive at 10 years;hazard ratio 1.87,95%confidence interval:1.21-2.90,P=0.004).Based on multivariate analysis,negative prognostic factors for overall survival included HER2 positivity,PR negativity,older age,Indian ethnicity and higher tumour stage.CONCLUSION Prevalence of HER2+ILC was 10.1%.HER2+ILC was more likely to have poorer prognostic features such as estrogen receptor negative,PR-and higher tumour grade,and have a poorer survival.
文摘BACKGROUND Epidermal growth factor receptor(EGFR)tyrosine-kinase inhibitors are widely used for the treatment of non-small-cell lung cancer with EGFR mutations.However,patients with rare,even compound EGFR mutations have different responses to EGFR-tyrosine-kinase inhibitors,which bring uncertainty to clinical treatment.CASE SUMMARY A 45-year-old female patient presented with a 3-mo history of cough and white sputum without chest pain.Chest computed tomography revealed lung spaceoccupying lesions and multiple lymphadenectasis.Bronchoscopy and pathology suggested lung adenocarcinoma.Compound variation of EGFR gene(exon 21 L858 R/V834 L)was detected in both tissue and circulating tumor deoxyribonucleic acid samples.As a result of next-generation sequencing and her family’s wishes,the patient was given oral treatment with icotinib hydrochloride(125 mg/d,tid)from March 21,2019 and has achieved stable disease for the last 1 year.CONCLUSION Non-small cell lung adenocarcinoma with EGFR L858 R/V834 L was treated successfully with icotinib,and it may be a new medication treatment option.
基金the Taipei Tzu Chi Hospital,Buddhist Tzu Chi Medical Foundation,No.TCRD-TPE-108-RT-4(3/3)and No.TCRD-TPE-109-59.
文摘Non-small-cell lung cancer(NSCLC)causes significant mortality worldwide.Patients with chronic renal failure have an increased risk of developing lungcancer.NSCLC Patients with chronic renal failure undergoing hemodialysis(HD)often exhibit poor performance,and chemotherapy is generally contraindicated.Oral epidermal growth factor receptor(EGFR)-tyrosine kinase inhibitors(TKIs)are effective treatment agents for NSCLC patients.However,the benefits andadverse effects of EGFR-TKIs in NSCLC undergoing HD are known.There are noclinical studies on the effects of EGFR-TKIs on NSCLC patients undergoing HD.We reviewed all previous case reports about EGFR-TKIs in NSCLC patientsundergoing HD.It is difficult to design studies about the effects of EGFR-TKIs inpatients undergoing HD,and this review is quite important.EGFR-TKIs are welltolerated in patients undergoing HD.The main routes of elimination of EGFRTKIsare metabolism via the liver,and renal elimination is minor.Therecommended doses and pharmacokinetics of these EGFR-TKIs for patientsundergoing HD are similar to those for patients with normal renal function.Theplasma protein binding of EGFR-TKIs is very high,and it is not necessary toadjust the dose after HD.In conclusion,EGFR-TKIs are effective and welltolerated in patients undergoing HD.
基金National Natural Science Foundation of China(No.81873396)China-Japan Friendship Hospital Horizontal project(No.2019-HX-69).
文摘Objective:To verify the efficacy of the Chinese medicine“Zhiyang Pingfu Liquid”on the lesion associated with Epidermal Growth Factor Receptor Inhibitors(EGFRIs).Methods:Female BN rats were divided into Control group and Gefitinib group randomly.The Gefitinib group was administered gefitinib for 21 days.After 21 days,the rats in the Gefitinib group were grouped again and randomly divided into Model group,Gefitinib+ZY group,and Gefitinib+NS group.Starting from day 22,rats in Gefitinib+ZY or NS were given different drugs for 7 days besides the other conditions are as the same as before.Observe the morphological changes and histopathological changes of the skin during the research.The changes of inflammatory factors such as TNF-αand IL-6 in the serum of were detected by ELISA.Results:The application of“Zhiyang Pingfu Liquid”for 7 days could significantly reduce the skin inflammation whether in gross or pathological view.The concentration of TNF-αand IL-6 in Gefitinib+ZY is significantly lower than those in the Model group(P=0.002,P=0.002)and there is no significant changes compared with the Control group(P=0.279,P=0.165).Conclusion:Chinese herbal“Zhiyang Pingfu Liquid”can reduce the lesion and inflammatory caused by EGFRIs.
