BACKGROUND The advent of cutting-edge systemic therapies has driven advances in the treatment of hepatocellular carcinoma(HCC),and therapeutic strategies with multiple modes of delivery have been shown to be more effi...BACKGROUND The advent of cutting-edge systemic therapies has driven advances in the treatment of hepatocellular carcinoma(HCC),and therapeutic strategies with multiple modes of delivery have been shown to be more efficacious than mono-therapy.However,the mechanisms underlying this innovative treatment modality have not been elucidated.AIM To evaluate the clinical efficacy of targeted therapy plus immunotherapy combined with hepatic arterial infusion chemotherapy(HAIC)of FOLFOX in patients with unresectable HCC.METHODS We enrolled 53 patients with unresectable HCC who received a combination of targeted therapy,immunotherapy,and HAIC of FOLFOX between December 2020 and June 2021 and assessed the efficacy and safety of the treatment regimen.RESULTS The objective response rate was 60.4%(32/53),complete response was 24.5%(13/53),partial response was 35.9%(19/53),and stable disease was 39.6%(21/53).The median duration of response and median progression-free survival were 9.1 and 13.9 months,respectively.The surgical conversion rate was 34.0%(18/53),and 1-year overall survival was 83.0%without critical complicating diseases or adverse events(AEs).CONCLUSION The regimen of HAIC of FOLFOX,targeted therapy,and immunotherapy was curative for patients with unresectable HCC,with no serious AEs and a high rate of surgical conversion.展开更多
Background:Liver transplantation(LT)is the“cure”therapy for patients with hepatocellular carcinoma(HCC).However,some patients encounter HCC recurrence after LT.Unfortunately,there is no effective methods to identify...Background:Liver transplantation(LT)is the“cure”therapy for patients with hepatocellular carcinoma(HCC).However,some patients encounter HCC recurrence after LT.Unfortunately,there is no effective methods to identify the LT patients who have high risk of HCC recurrence and would benefit from adjuvant targeted therapy.The present study aimed to establish a scoring system to predict HCC recurrence of HCC patients after LT among the Chinese population,and to evaluate whether these patients are suitable for adjuvant targeted therapy.Methods:Clinical data of HCC patients who underwent LT from March 2015 to June 2019 were retrospectively collected and analyzed.Results:A total of 201 patients were included in the study.The multivariate Cox analysis suggested that preoperative alpha-fetoprotein(AFP)>200μg/L(HR=2.666,95%CI:1.515-4.690;P=0.001),glutamyl transferase(GGT)>96 U/L(HR=1.807,95%CI:1.012-3.224;P=0.045),and exceeding the Hangzhou criteria(HR=2.129,95%CI:1.158-3.914;P=0.015)were independent risk factors for poor disease-free survival(DFS)in patients with HCC who underwent LT.We established an AFP-GGT-Hangzhou(AGH)scoring system based on these factors,and divided cases into high-,moderate-,and low-risk groups.The differences in overall survival(OS)and disease-free survival(DFS)rates among the three groups were significant(P<0.05).The efficacy of the AGH scoring system to predict DFS was better than that of the Hangzhou criteria,UCSF criteria,Milan criteria,and TNM stage.Only in the high-risk group,we found that lenvatinib significantly improved prognosis compared with that of the control group(P<0.05).Conclusions:The AGH scoring system provides a convenient and effective way to predict HCC recurrence after LT in HCC patients in China.Patients with a high-risk AGH score may benefit from lenvatinib adjuvant therapy after LT.展开更多
Hepatocellular carcinoma(HCC)is a common malignant tumor that affecting many people's lives globally.The common risk factors for HCC include being overweight and obese.The liver is the center of lipid metabolism,s...Hepatocellular carcinoma(HCC)is a common malignant tumor that affecting many people's lives globally.The common risk factors for HCC include being overweight and obese.The liver is the center of lipid metabolism,synthesizing most cholesterol and fatty acids.Abnormal lipid metabolism is a significant feature of metabolic reprogramming in HCC and affects the prognosis of HCC patients by regulating inflammatory responses and changing the immune microenvironment.Targeted therapy and immunotherapy are being explored as the primary treatment strategies for HCC patients with unresectable tumors.Here,we detail the specific changes of lipid metabolism in HCC and its impact on both these therapies for HCC.HCC treatment strategies aimed at targeting lipid metabolism and how to integrate them with targeted therapy or immunotherapy rationally are also presented.展开更多
Pancreatic adenocarcinoma(PDAC)is a fatal disease with a 5-year survival rate of 8%and a median survival of 6 mo.In PDAC,several mutations in the genes are involved,with Kirsten rat sarcoma oncogene(90%),cyclin-depend...Pancreatic adenocarcinoma(PDAC)is a fatal disease with a 5-year survival rate of 8%and a median survival of 6 mo.In PDAC,several mutations in the genes are involved,with Kirsten rat sarcoma oncogene(90%),cyclin-dependent kinase inhibitor 2A(90%),and tumor suppressor 53(75%–90%)being the most common.Mothers against decapentaplegic homolog 4 represents 50%.In addition,the selfpreserving cancer stem cells,dense tumor microenvironment(fibrous accounting for 90%of the tumor volume),and suppressive and relatively depleted immune niche of PDAC are also constitutive and relevant elements of PDAC.Molecular targeted therapy is widely utilized and effective in several solid tumors.In PDAC,targeted therapy has been extensively evaluated;however,survival improvement of this aggressive disease using a targeted strategy has been minimal.There is currently only one United States Food and Drug Administration-approved targeted therapy for PDAC–erlotinib,but the absolute benefit of erlotinib in combination with gemcitabine is also minimal(2 wk).In this review,we summarize current targeted therapies and clinical trials targeting dysregulated signaling pathways and components of the PDAC oncogenic process,analyze possible reasons for the lack of positive results in clinical trials,and suggest ways to improve them.We also discuss emerging trends in targeted therapies for PDAC:combining targeted inhibitors of multiple pathways.The PubMed database and National Center for Biotechnology Information clinical trial website(www.clinicaltrials.gov)were queried to identify completed and published(PubMed)and ongoing(clinicaltrials.gov)clinical trials(from 2003-2022)using the keywords pancreatic cancer and targeted therapy.The PubMed database was also queried to search for information about the pathogenesis and molecular pathways of pancreatic cancer using the keywords pancreatic cancer and molecular pathways.展开更多
Gall bladder cancer(GBC)is becoming a very devastating form of hepatobiliary cancer in India.Every year new cases of GBC are quite high in India.Despite recent advanced multimodality treatment options,the survival of ...Gall bladder cancer(GBC)is becoming a very devastating form of hepatobiliary cancer in India.Every year new cases of GBC are quite high in India.Despite recent advanced multimodality treatment options,the survival of GBC patients is very low.If the disease is diagnosed at the advanced stage(with local nodal metastasis or distant metastasis)or surgical resection is inoperable,the prognosis of those patients is very poor.So,perspectives of targeted therapy are being taken.Targeted therapy includes hormone therapy,proteasome inhibitors,signal transduction and apoptosis inhibitors,angiogenesis inhibitors,and immunotherapeutic agents.One such signal transduction inhibitor is the specific short interfering RNA(siRNA)or short hairpin RNA(shRNA).For developing siRNAmediated therapy shRNA,although several preclinical studies to evaluate the efficacy of these key molecules have been performed using gall bladder cells,many more clinical trials are required.To date,many such genes have been identified.This review will discuss the recently identified genes associated with GBC and those that have implications in its treatment by siRNA or shRNA.展开更多
Background: There are currently no recognised biomarkers that identify predictive groups of benefit in patients with hepatocellular carcinoma receiving immune-combined targeted therapy, for which we explored the value...Background: There are currently no recognised biomarkers that identify predictive groups of benefit in patients with hepatocellular carcinoma receiving immune-combined targeted therapy, for which we explored the value of peripheral blood markers as markers of their prognosis. Methods: Patients who underwent anti-PD-1 combination targeted therapy for hepatocellular carcinoma from 1 January 2019 to 31 December 2021 at the First Affiliated Hospital of Chongqing Medical University were retrospectively analysed. The data collected were analysed by R software. Results: A total of 41 cases were included in our study. The optimal threshold values of peripheral blood markers were obtained by plotting ROC curves and grouping patients. Survival analysis of the grouped patients showed statistically significant differences in survival between the different groups for Platelet-lymphocyte ratio (PLR, P = 0.0022), Monocyte-lymphocyte ratio (MLR, P = 0.042), Fibrinogen-Lymphocyte Ratio (FLR, P = 0.0009), Prognostic nutritional index (PIN, P = 0.0005), and Fibrinogen-albumin ratio (FAR, P = 0.0144). An ANOVA was performed on the basic conditions of the patients between the different groups, except for the statistically significant difference in BCLC stage (P = 0.0128) between the high MLR and low MLR groups, there was no statistically significant difference in age, gender, BCLC stage, and hepatitis status between the groups. COX regression analysis showed that BCLC stage, FAR, FLR and PIN were risk factors associated with the prognosis of patients receiving targeted combination immunotherapy for hepatocellular carcinoma, and FLR was an independent risk factor associated with the prognosis of patients receiving targeted combination immunotherapy for hepatocellular carcinoma. Conclusions: We found that peripheral blood markers are promising biomarkers for predicting the prognosis of patients with hepatocellular carcinoma receiving anti-PD-1 combined with targeted therapy, and this study identified FLR as an independent risk factor for the prognosis of patients having advanced hepatocellular carcinoma treated with anti-PD-1 combined with targeted therapy.展开更多
Facial infiltrating lipomatosis(FIL)is a congenital asymmetrical deformity of the maxillofacial region that can significantly affect a patient’s facial appearance and function.With the development of sequencing techn...Facial infiltrating lipomatosis(FIL)is a congenital asymmetrical deformity of the maxillofacial region that can significantly affect a patient’s facial appearance and function.With the development of sequencing technologies,PIK3CA mutations are considered among the potential etiologies of FIL.The management and treatment of FIL involves plastic surgery;more recently,an improved understanding of its pathogenesis has given rise to new treatment options,including targeted therapy.Here we report the clinical data of two patients diagnosed with FIL and present current curative concepts.展开更多
Locoregional therapies(LRTs)of hepatocellular carcinoma(HCC)represented by ablation and TACE has become the main means for the clinical treatment of unresectable HCC.Among these,TACE is used throughout the stageⅠb to...Locoregional therapies(LRTs)of hepatocellular carcinoma(HCC)represented by ablation and TACE has become the main means for the clinical treatment of unresectable HCC.Among these,TACE is used throughout the stageⅠb toⅢb of HCC treatment.In recent years,immunotherapy led by immune checkpoint inhibitors has become a hot direction in clinical research.At the same time,targeted drugs such as Sorafenib and Apatinib have played an important role in the treatment and complementary therapy of advanced HCC,and their clinical application has been quite mature.HCC is the sixth most common malignant tumor in the world.When it comes to its treatment,different therapies have different indications,and their individual efficacies are not satisfactory,which makes the exploration of the use of combination therapy in HCC treatment become a new trend.In this paper,the status of the three therapies and the progress of their combined application are briefly reviewed.展开更多
Hepatocellular carcinoma(HCC),one of the most common malignant tumors in China,severely threatens the life and health of patients.In recent years,precision medicine,clinical diagnoses,treatments,and innovative researc...Hepatocellular carcinoma(HCC),one of the most common malignant tumors in China,severely threatens the life and health of patients.In recent years,precision medicine,clinical diagnoses,treatments,and innovative research have led to important breakthroughs in HCC care.The discovery of new biomarkers and the promotion of liquid biopsy technologies have greatly facilitated the early diagnosis and treatment of HCC.Progress in targeted therapy and immunotherapy has provided more choices for precise HCC treatment.Multiomics technologies,such as genomics,transcriptomics,and metabolomics,have enabled deeper understanding of the occurrence and development mechanisms,heterogeneity,and genetic mutation characteristics of HCC.The continued promotion and accurate typing of HCC,accurate guidance of treatment,and accurate prognostication have provided more treatment opportunities and prolonged survival timelines for patients with HCC.Innovative HCC research providing an in-depth understanding of the biological characteristics of HCC will be translated into accurate clinical practices for the diagnosis and treatment of HCC.展开更多
Hepatocellular carcinoma(HCC)is one of the most common malignancies,and its treatment is limited.With the understanding of key genes and signaling pathways in the occurrence and development of HCC,targeted drugs with ...Hepatocellular carcinoma(HCC)is one of the most common malignancies,and its treatment is limited.With the understanding of key genes and signaling pathways in the occurrence and development of HCC,targeted drugs with high selectivity and low toxicity have been developed continuously,bringing a variety of options for the treatment of advanced HCC.In this article,the research progress on representative drugs of targeted therapy and potential therapeutic targets for HCC are reviewed.展开更多
The last two decades have witnessed a paradigm shift from cytotoxic drugs to targeted therapy in medical oncol?ogy and pharmaceutical innovation. Inspired by breakthroughs in molecular and cellular biology, a number o...The last two decades have witnessed a paradigm shift from cytotoxic drugs to targeted therapy in medical oncol?ogy and pharmaceutical innovation. Inspired by breakthroughs in molecular and cellular biology, a number of novel synthesized chemical compounds and recombinant antibodies have been developed to selectively target oncogenic signaling pathways in a broad array of tumor types. Although targeted therapeutic agents show impressive clinical eicacy and minimized adverse efects compared with traditional treatments, the challenging drug?resistant issue has also emerged to limit their beneits to cancer patients. In this regard, we aim to improve targeted therapy by present?ing a systematic framework regarding the drug resistance mechanisms and alternative approaches to re?sensitize cancer cells/tissues therapeutically.展开更多
BACKGROUND Anaplastic thyroid carcinoma(ATC),also called undifferentiated thyroid cancer,is the least common but most aggressive and deadly thyroid gland malignancy of all thyroid cancers[1].It has poor prognosis,and ...BACKGROUND Anaplastic thyroid carcinoma(ATC),also called undifferentiated thyroid cancer,is the least common but most aggressive and deadly thyroid gland malignancy of all thyroid cancers[1].It has poor prognosis,and is the leading cause of death from malignant thyroid tumors.The one-year survival rate is 20%,with a median overall survival(OS)of only 5 mo[2].The aim of this report is to provide our experience in the diagnosis and treatment of ATC.CASE SUMMARY A patient with a thyroid mass underwent surgical treatment after developing symptoms of hoarseness.The resected tumor was pathologically diagnosed as ATC.Imaging examination revealed organ and lymph node metastasis.After multiple cycles of chemotherapy and local radiotherapy,the metastases were not relieved and gradually increased in size and new metastases appeared.The patient immediately received immunotherapy combined with targeted therapy.During treatment,immune-related adverse reactions occurred,which were improved after symptomatic treatment,and tolerated by the patient.The OS of the patient was more than 30 mo after immunotherapy combined with targeted therapy.CONCLUSION For metastatic ATC,surgical treatment,radiotherapy and chemotherapy have no significant effect on remission of the disease.However,immunotherapy has made a breakthrough in the treatment of ATC。展开更多
BACKGROUND Neoadjuvant or perioperative chemotherapy combined with surgery can reduce postoperative recurrence and improve the long-term survival rate of patients with locally advanced resectable gastric carcinoma.Niv...BACKGROUND Neoadjuvant or perioperative chemotherapy combined with surgery can reduce postoperative recurrence and improve the long-term survival rate of patients with locally advanced resectable gastric carcinoma.Nivolumab combined with chemotherapy has been recommended by the National Comprehensive Cancer Network guidelines as a first-line therapy for advanced gastric carcinoma/adenocarcinoma of the gastroesophageal junction and serves as the basis for immunotherapy combined with chemotherapy to become a neoadjuvant therapy.Herein,we report a case in which pathologic complete response was achieved by neoadjuvant administration of toripalimab,Herceptin,and docetaxel,oxaliplatin,calcium folinate,and fluorouracil(FLOT)chemotherapy followed by surgery for human epidermal growth factor receptor 2(HER2)-and programmed deathligand 1(PD-L1)-positive locally advanced gastric carcinoma.We hope that this case will shed some light on neoadjuvant therapy for gastric carcinoma.CASE SUMMARY The patient was diagnosed with locally advanced adenocarcinoma of the cardia.Immunohistochemistry of the baseline tissues suggested that the tissues were HER2-(fluorescent in situ hybridization)and PD-L1-positive(combined positive score=1).The patient underwent surgery following a four-cycle neoadjuvant therapy comprising Herceptin,toripalimab,and FLOT chemotherapy.The postoperative pathological findings showed mild atypical hyperplasia of the local glands with chronic mucosal inflammation(proximal stomach),no clear residual tumor(tumor regression grade 0),no regional lymph node metastasis,and negative upper and lower cut ends.The levels of tumor markers were reduced to normal levels after re-examination.With good postoperative recovery,the four-cycle preoperative chemotherapy was continued at the same dosage as that previously administered.After the treatment,the patient was monitored every 3 mo with a follow-up of 12 mo(4 times).As of February 27,2022,he was in a good condition without disease progression.The clinical trial registration number is E2019401.CONCLUSION There are many ongoing studies on neoadjuvant immunotherapy combined with chemotherapy or radiotherapy;however,most of these studies are phase II studies with small cohorts.According to the results of some current studies,these combined regimens have shown promising results in terms of efficacy and safety.However,the clinical efficacy and safety of the neoadjuvant therapies used in these combined regimens need to be confirmed by additional prospective phase III clinical trials,and further exploration of molecular markers for effective populations is required.展开更多
Gastrointestinal(GI)cancer remains the deadliest cancer in the world.The current standard treatment for GI cancer focuses on 5-fluorouracil-based chemotherapeutic regimens and surgery,and molecular-targeted therapy is...Gastrointestinal(GI)cancer remains the deadliest cancer in the world.The current standard treatment for GI cancer focuses on 5-fluorouracil-based chemotherapeutic regimens and surgery,and molecular-targeted therapy is expected to be a more effective and less toxic therapeutic strategy for GI cancer.There is wellestablished evidence for the use of epidermal growth factor receptor-targeted and vascular endothelial growth factor-targeted antibodies,which should routinely be incorporated into treatment strategies for GI cancer.Other potential therapeutic targets involve the PI3K/AKT pathway,tumor growth factor-βpathway,mesenchymal-epithelial transition pathway,WNT pathway,poly(ADP-ribose)polymerase,and immune checkpoints.Many clinical trials assessing the agents of targeted therapy are underway and have presented promising and thoughtprovoking results.With the development of molecular biology techniques,we can identify more targetable molecular alterations in larger patient populations with GI cancer.Targeting these molecules will allow us to reach the goal of precision medicine and improve the outcomes of patients with GI cancer.展开更多
Modern therapy of acute myeloid leukemia(AML)began in 1973 with the first report of the successful combination of daunorubicin and cytarabine,which led to complete remission in approximately 45%of patients.Accurate AM...Modern therapy of acute myeloid leukemia(AML)began in 1973 with the first report of the successful combination of daunorubicin and cytarabine,which led to complete remission in approximately 45%of patients.Accurate AML diagnosis was dependent on morphology,aided initially only by cytochemistry.Unlike acute lymphoblastic leukemia(ALL),immunophenotyping offered little in the diagnosis of AML,at least during the 1970s and 1980s.The advent of reliable cytogenetics changed the entire prognostic outlook of AML.With karyotypic analysis,different groups of AML could be classified and stratified for various therapies.Unique mutational profiling was a major advance in further categorizing AML patients,aided by the immunophenotypic identification of antigenic markers on the cells.All these advances were occurring as the understanding of the importance of the tumor burden—known as minimal residual disease(MRD)—became crucial for the management of AML patients.The efficacy of MRD has rapidly progressed in the past decade,from a specificity of 103 with immunophenotyping to 104 with polymerase chain reaction(PCR),which is only appropriate for some patients with AML,and finally to 105 or even 106 cells with the extraordinary sensitivity of next-generation sequencing(NGS).All of these advances have promoted the concept of personalized medicine,which has led to the advent of targeted agents that can accurately be used for specific diagnostic subtypes.Responses can be predicted and measured accurately.Such targeted agents have now become a cornerstone in the management of AML,increasing effi-cacy and dramatically reducing toxicity.The focus of this review is on one of the most well-studied targeted agents in AML:the FMS-like tyrosine kinase 3(FLT3)inhibitors,which have impacted the prognostication and therapeutics of AML.This review selectively discusses the FLT3 inhibitors in detail,as a model for the other burgeoning targeted agents that have already been approved,as well as those that are currently in development.展开更多
BACKGROUND Targeted therapy(TT)has resulted in controversial efficacy as first-line treatment for biliary tract cancer(BTC).More efficacy comparisons are required to clarify the overall effects of chemotherapy(CT)comb...BACKGROUND Targeted therapy(TT)has resulted in controversial efficacy as first-line treatment for biliary tract cancer(BTC).More efficacy comparisons are required to clarify the overall effects of chemotherapy(CT)combined with TT and CT alone on advanced BTC.AIM To conduct a meta-analysis of the available evidence on the efficacy of CT combined with TT for advanced BTC.METHODS The PubMed,EMBASE,ClinicalTrials,Scopus and Cochrane Library databases were systematically searched for relevant studies published from inception to August 2022.Only randomized clinical trials(RCTs)including comparisons between the combination of gemcitabine-based CT with TT and CT alone as firstline treatment for advanced BTC were eligible(PROSPERO-CRD42022313001).The odds ratios(ORs)for the objective response rate(ORR)and hazard ratios(HRs)for both progression-free survival(PFS)and overall survival(OS)were calculated and analyzed.Subgroup analyses based on different targeted agents,CT regimens and tumor locations were prespecified.RESULTS Nine RCTs with a total of 1361 individuals were included and analyzed.The overall analysis showed a significant improvement in ORR in patients treated with CT+TT compared to those treated with CT alone(OR=1.43,95%CI:1.11-1.86,P=0.007)but no difference in PFS or OS.Similar trends were observed in the subgroup treated with agents targeting epidermal growth factor receptor(OR=1.67,95%CI:1.17-2.37,P=0.004)but not in the subgroups treated with agents targeting vascular endothelial growth factor receptor or mesenchymal-epithelial transition factor.Notably,patients who received a CT regimen of gemcitabine+oxaliplatin in the CT+TT arm had both a higher ORR(OR=1.75,95%CI:1.20-2.56,P=0.004)and longer PFS(HR=0.83,95%CI:0.70-0.99,P=0.03)than those in the CT-only arm.Moreover,patients with cholangiocarcinoma treated with CT+TT had significantly increased ORR and PFS(ORR,OR=2.06,95%CI:1.27-3.35,PFS,HR=0.79,95%CI:0.66-0.94).CONCLUSION CT+TT is a potential first-line treatment for advanced BTC that leads to improved tumor control and survival outcomes,and highlighting the importance of CT regimens and tumor types in the application of TT.展开更多
BACKGROUND Apocrine carcinoma of the breast is a special type of invasive ductal carcinoma of the breast that is rare in clinical practice.Neoadjuvant therapy,especially neoadjuvant targeted therapy,has rarely been re...BACKGROUND Apocrine carcinoma of the breast is a special type of invasive ductal carcinoma of the breast that is rare in clinical practice.Neoadjuvant therapy,especially neoadjuvant targeted therapy,has rarely been reported for apocrine carcinoma of the breast.CASE SUMMARY A 63-year-old woman presented with apocrine carcinoma of the left breast underwent core needle biopsy.The patient was diagnosed with apocrine carcinoma by immunohistochemical staining and negative hormone status(estrogen receptor and progesterone receptor)but showed overexpression of human epidermal factor receptor 2(HER-2).Moreover,positive expression of androgen receptor(approximately 60%)and gross cystic disease fluid protein 15 was observed.The patient was treated with neoadjuvant targeted therapy consisting of the TCH regimen(docetaxel,carboplatin area under curve 6 and trastuzumab)every 21 d.The mass in the left breast was significantly reduced,and pain in the breast and left upper arm also improved.CONCLUSION HER-2 positive apocrine carcinoma of the breast can be improved by neoadjuvant chemotherapy combined with targeted therapy.展开更多
Although targeted therapies and immunotherapies have been effective againstseveral malignancies, the respective monotherapies are limited by low and/orshort-term responses. Specific inhibitors of oncogenic signaling p...Although targeted therapies and immunotherapies have been effective againstseveral malignancies, the respective monotherapies are limited by low and/orshort-term responses. Specific inhibitors of oncogenic signaling pathways andtumor-associated angiogenesis can activate the anti-tumor immune responses byincreasing tumor antigen presentation or intratumor T cell infiltration. Additionalinsights into the effects and mechanisms of targeted therapies on the induction ofanti-tumor immunity will facilitate development of rational and effective combinationstrategies that synergize rapid tumor regression and durable response. Inthis review, we have summarized the recent combinations of targeted therapiesand immunotherapies, along with the associated clinical challenges.展开更多
In recent years, with the deepening of research on the pathogenesis of renal cell carcinoma, anti-VEGF receptor inhibitors and mTOR inhibitors have been produced, making metastatic renal cell carcinoma into the era of...In recent years, with the deepening of research on the pathogenesis of renal cell carcinoma, anti-VEGF receptor inhibitors and mTOR inhibitors have been produced, making metastatic renal cell carcinoma into the era of targeted therapy. This article analyzes the latest research results at home and abroad. For patients with metastatic renal cell carcinoma, sunitinib and pizopanib are the first choice for targeted drugs. The drug dose starts from the standard dose, and the disease can be increased as appropriate when the disease progresses;When responding, it should be treated or reduced in time. When using an anti-VEGF inhibitor, the patient's blood pressure should be closely monitored. When the patient has high blood sugar or diabetes, anti-VEGF inhibitors should be preferred.展开更多
We report two cases of hepatic encephalopathy caused by molecular targeted drugs after the Transjugular intrahepatic portosystemic shunt(TIPS)procedure in our center.The liver toxicities and anti-angiogenic effects in...We report two cases of hepatic encephalopathy caused by molecular targeted drugs after the Transjugular intrahepatic portosystemic shunt(TIPS)procedure in our center.The liver toxicities and anti-angiogenic effects induced by targeted drugs may generate an imbalance in ammonia metabolism,elevating blood ammonia levels.TIPS diverts partial blood supply from the liver,aggravates liver impairment,and shunts ammonia-rich blood from the intestine into the systemic circulation.These may be the mechanisms leading to hepatic encephalopathy caused by molecular targeted drugs following TIPS.When clinicians choose molecular targeted therapy as the second or third targeted therapy for patients who have undergone TIPS,the consequence of drug-induced hepatic encephalopathy should also be considered.展开更多
基金This study was reviewed and approved by the Ethics Committee of Zhongshan People’s Hospital(Approval No.2022-029).
文摘BACKGROUND The advent of cutting-edge systemic therapies has driven advances in the treatment of hepatocellular carcinoma(HCC),and therapeutic strategies with multiple modes of delivery have been shown to be more efficacious than mono-therapy.However,the mechanisms underlying this innovative treatment modality have not been elucidated.AIM To evaluate the clinical efficacy of targeted therapy plus immunotherapy combined with hepatic arterial infusion chemotherapy(HAIC)of FOLFOX in patients with unresectable HCC.METHODS We enrolled 53 patients with unresectable HCC who received a combination of targeted therapy,immunotherapy,and HAIC of FOLFOX between December 2020 and June 2021 and assessed the efficacy and safety of the treatment regimen.RESULTS The objective response rate was 60.4%(32/53),complete response was 24.5%(13/53),partial response was 35.9%(19/53),and stable disease was 39.6%(21/53).The median duration of response and median progression-free survival were 9.1 and 13.9 months,respectively.The surgical conversion rate was 34.0%(18/53),and 1-year overall survival was 83.0%without critical complicating diseases or adverse events(AEs).CONCLUSION The regimen of HAIC of FOLFOX,targeted therapy,and immunotherapy was curative for patients with unresectable HCC,with no serious AEs and a high rate of surgical conversion.
基金supported by grants from the National Natural Science Foundation of China(81873874 and 82071797)Clinical Research Plan of SHDC(SHDC2020CR2021B and SHDC2020CR5012)+1 种基金Foundation of Science and Technology Commission of Shanghai Municipality(20Y11908500)Foundation of Shanghai Municipal Health Commission(201940032)。
文摘Background:Liver transplantation(LT)is the“cure”therapy for patients with hepatocellular carcinoma(HCC).However,some patients encounter HCC recurrence after LT.Unfortunately,there is no effective methods to identify the LT patients who have high risk of HCC recurrence and would benefit from adjuvant targeted therapy.The present study aimed to establish a scoring system to predict HCC recurrence of HCC patients after LT among the Chinese population,and to evaluate whether these patients are suitable for adjuvant targeted therapy.Methods:Clinical data of HCC patients who underwent LT from March 2015 to June 2019 were retrospectively collected and analyzed.Results:A total of 201 patients were included in the study.The multivariate Cox analysis suggested that preoperative alpha-fetoprotein(AFP)>200μg/L(HR=2.666,95%CI:1.515-4.690;P=0.001),glutamyl transferase(GGT)>96 U/L(HR=1.807,95%CI:1.012-3.224;P=0.045),and exceeding the Hangzhou criteria(HR=2.129,95%CI:1.158-3.914;P=0.015)were independent risk factors for poor disease-free survival(DFS)in patients with HCC who underwent LT.We established an AFP-GGT-Hangzhou(AGH)scoring system based on these factors,and divided cases into high-,moderate-,and low-risk groups.The differences in overall survival(OS)and disease-free survival(DFS)rates among the three groups were significant(P<0.05).The efficacy of the AGH scoring system to predict DFS was better than that of the Hangzhou criteria,UCSF criteria,Milan criteria,and TNM stage.Only in the high-risk group,we found that lenvatinib significantly improved prognosis compared with that of the control group(P<0.05).Conclusions:The AGH scoring system provides a convenient and effective way to predict HCC recurrence after LT in HCC patients in China.Patients with a high-risk AGH score may benefit from lenvatinib adjuvant therapy after LT.
基金Supported by National Natural Science Foundation of China,No.81970453,and No.82270634Shanghai Science and Technology Innovation Action Plan Project,No.20XD1405100.
文摘Hepatocellular carcinoma(HCC)is a common malignant tumor that affecting many people's lives globally.The common risk factors for HCC include being overweight and obese.The liver is the center of lipid metabolism,synthesizing most cholesterol and fatty acids.Abnormal lipid metabolism is a significant feature of metabolic reprogramming in HCC and affects the prognosis of HCC patients by regulating inflammatory responses and changing the immune microenvironment.Targeted therapy and immunotherapy are being explored as the primary treatment strategies for HCC patients with unresectable tumors.Here,we detail the specific changes of lipid metabolism in HCC and its impact on both these therapies for HCC.HCC treatment strategies aimed at targeting lipid metabolism and how to integrate them with targeted therapy or immunotherapy rationally are also presented.
基金Supported by The National Key Research and Development Program of China,No.2021YFF1201300The Special Foundation of Wu Jieping Medical Foundation for Clinical Scientific Research,No.320.6750.2022-10-95.
文摘Pancreatic adenocarcinoma(PDAC)is a fatal disease with a 5-year survival rate of 8%and a median survival of 6 mo.In PDAC,several mutations in the genes are involved,with Kirsten rat sarcoma oncogene(90%),cyclin-dependent kinase inhibitor 2A(90%),and tumor suppressor 53(75%–90%)being the most common.Mothers against decapentaplegic homolog 4 represents 50%.In addition,the selfpreserving cancer stem cells,dense tumor microenvironment(fibrous accounting for 90%of the tumor volume),and suppressive and relatively depleted immune niche of PDAC are also constitutive and relevant elements of PDAC.Molecular targeted therapy is widely utilized and effective in several solid tumors.In PDAC,targeted therapy has been extensively evaluated;however,survival improvement of this aggressive disease using a targeted strategy has been minimal.There is currently only one United States Food and Drug Administration-approved targeted therapy for PDAC–erlotinib,but the absolute benefit of erlotinib in combination with gemcitabine is also minimal(2 wk).In this review,we summarize current targeted therapies and clinical trials targeting dysregulated signaling pathways and components of the PDAC oncogenic process,analyze possible reasons for the lack of positive results in clinical trials,and suggest ways to improve them.We also discuss emerging trends in targeted therapies for PDAC:combining targeted inhibitors of multiple pathways.The PubMed database and National Center for Biotechnology Information clinical trial website(www.clinicaltrials.gov)were queried to identify completed and published(PubMed)and ongoing(clinicaltrials.gov)clinical trials(from 2003-2022)using the keywords pancreatic cancer and targeted therapy.The PubMed database was also queried to search for information about the pathogenesis and molecular pathways of pancreatic cancer using the keywords pancreatic cancer and molecular pathways.
文摘Gall bladder cancer(GBC)is becoming a very devastating form of hepatobiliary cancer in India.Every year new cases of GBC are quite high in India.Despite recent advanced multimodality treatment options,the survival of GBC patients is very low.If the disease is diagnosed at the advanced stage(with local nodal metastasis or distant metastasis)or surgical resection is inoperable,the prognosis of those patients is very poor.So,perspectives of targeted therapy are being taken.Targeted therapy includes hormone therapy,proteasome inhibitors,signal transduction and apoptosis inhibitors,angiogenesis inhibitors,and immunotherapeutic agents.One such signal transduction inhibitor is the specific short interfering RNA(siRNA)or short hairpin RNA(shRNA).For developing siRNAmediated therapy shRNA,although several preclinical studies to evaluate the efficacy of these key molecules have been performed using gall bladder cells,many more clinical trials are required.To date,many such genes have been identified.This review will discuss the recently identified genes associated with GBC and those that have implications in its treatment by siRNA or shRNA.
文摘Background: There are currently no recognised biomarkers that identify predictive groups of benefit in patients with hepatocellular carcinoma receiving immune-combined targeted therapy, for which we explored the value of peripheral blood markers as markers of their prognosis. Methods: Patients who underwent anti-PD-1 combination targeted therapy for hepatocellular carcinoma from 1 January 2019 to 31 December 2021 at the First Affiliated Hospital of Chongqing Medical University were retrospectively analysed. The data collected were analysed by R software. Results: A total of 41 cases were included in our study. The optimal threshold values of peripheral blood markers were obtained by plotting ROC curves and grouping patients. Survival analysis of the grouped patients showed statistically significant differences in survival between the different groups for Platelet-lymphocyte ratio (PLR, P = 0.0022), Monocyte-lymphocyte ratio (MLR, P = 0.042), Fibrinogen-Lymphocyte Ratio (FLR, P = 0.0009), Prognostic nutritional index (PIN, P = 0.0005), and Fibrinogen-albumin ratio (FAR, P = 0.0144). An ANOVA was performed on the basic conditions of the patients between the different groups, except for the statistically significant difference in BCLC stage (P = 0.0128) between the high MLR and low MLR groups, there was no statistically significant difference in age, gender, BCLC stage, and hepatitis status between the groups. COX regression analysis showed that BCLC stage, FAR, FLR and PIN were risk factors associated with the prognosis of patients receiving targeted combination immunotherapy for hepatocellular carcinoma, and FLR was an independent risk factor associated with the prognosis of patients receiving targeted combination immunotherapy for hepatocellular carcinoma. Conclusions: We found that peripheral blood markers are promising biomarkers for predicting the prognosis of patients with hepatocellular carcinoma receiving anti-PD-1 combined with targeted therapy, and this study identified FLR as an independent risk factor for the prognosis of patients having advanced hepatocellular carcinoma treated with anti-PD-1 combined with targeted therapy.
基金supported by the Major and Key Cultivation Projects of Shanghai Ninth People’s Hospital, Shanghai Jiao Tong university School of Medicine (grant no. JYZP005)Project of Biobank from Shanghai Ninth People’s Hospital, Shanghai Jiao Tong University School of Medicine (grant no. YBKA202209)Rare Disease Registration Platform of Shanghai Ninth People’s Hospital, Shanghai Jiao Tong University School of Medicine (grant no. JYHJB02)
文摘Facial infiltrating lipomatosis(FIL)is a congenital asymmetrical deformity of the maxillofacial region that can significantly affect a patient’s facial appearance and function.With the development of sequencing technologies,PIK3CA mutations are considered among the potential etiologies of FIL.The management and treatment of FIL involves plastic surgery;more recently,an improved understanding of its pathogenesis has given rise to new treatment options,including targeted therapy.Here we report the clinical data of two patients diagnosed with FIL and present current curative concepts.
基金supported by National Key Research and Development Program of China Grant under No.2019YFC0118100。
文摘Locoregional therapies(LRTs)of hepatocellular carcinoma(HCC)represented by ablation and TACE has become the main means for the clinical treatment of unresectable HCC.Among these,TACE is used throughout the stageⅠb toⅢb of HCC treatment.In recent years,immunotherapy led by immune checkpoint inhibitors has become a hot direction in clinical research.At the same time,targeted drugs such as Sorafenib and Apatinib have played an important role in the treatment and complementary therapy of advanced HCC,and their clinical application has been quite mature.HCC is the sixth most common malignant tumor in the world.When it comes to its treatment,different therapies have different indications,and their individual efficacies are not satisfactory,which makes the exploration of the use of combination therapy in HCC treatment become a new trend.In this paper,the status of the three therapies and the progress of their combined application are briefly reviewed.
基金This study was supported by funding from the Science Technology and Innovation Committee of Shenzhen Municipality(Grant No.2019N002)Capital's Funds for Health Improvement and Research(Grant No.Z181100001718075).
文摘Hepatocellular carcinoma(HCC),one of the most common malignant tumors in China,severely threatens the life and health of patients.In recent years,precision medicine,clinical diagnoses,treatments,and innovative research have led to important breakthroughs in HCC care.The discovery of new biomarkers and the promotion of liquid biopsy technologies have greatly facilitated the early diagnosis and treatment of HCC.Progress in targeted therapy and immunotherapy has provided more choices for precise HCC treatment.Multiomics technologies,such as genomics,transcriptomics,and metabolomics,have enabled deeper understanding of the occurrence and development mechanisms,heterogeneity,and genetic mutation characteristics of HCC.The continued promotion and accurate typing of HCC,accurate guidance of treatment,and accurate prognostication have provided more treatment opportunities and prolonged survival timelines for patients with HCC.Innovative HCC research providing an in-depth understanding of the biological characteristics of HCC will be translated into accurate clinical practices for the diagnosis and treatment of HCC.
基金the Research Project 2017 of Health and Family Planning Commission of Hunan Province(A2017015).
文摘Hepatocellular carcinoma(HCC)is one of the most common malignancies,and its treatment is limited.With the understanding of key genes and signaling pathways in the occurrence and development of HCC,targeted drugs with high selectivity and low toxicity have been developed continuously,bringing a variety of options for the treatment of advanced HCC.In this article,the research progress on representative drugs of targeted therapy and potential therapeutic targets for HCC are reviewed.
文摘The last two decades have witnessed a paradigm shift from cytotoxic drugs to targeted therapy in medical oncol?ogy and pharmaceutical innovation. Inspired by breakthroughs in molecular and cellular biology, a number of novel synthesized chemical compounds and recombinant antibodies have been developed to selectively target oncogenic signaling pathways in a broad array of tumor types. Although targeted therapeutic agents show impressive clinical eicacy and minimized adverse efects compared with traditional treatments, the challenging drug?resistant issue has also emerged to limit their beneits to cancer patients. In this regard, we aim to improve targeted therapy by present?ing a systematic framework regarding the drug resistance mechanisms and alternative approaches to re?sensitize cancer cells/tissues therapeutically.
文摘BACKGROUND Anaplastic thyroid carcinoma(ATC),also called undifferentiated thyroid cancer,is the least common but most aggressive and deadly thyroid gland malignancy of all thyroid cancers[1].It has poor prognosis,and is the leading cause of death from malignant thyroid tumors.The one-year survival rate is 20%,with a median overall survival(OS)of only 5 mo[2].The aim of this report is to provide our experience in the diagnosis and treatment of ATC.CASE SUMMARY A patient with a thyroid mass underwent surgical treatment after developing symptoms of hoarseness.The resected tumor was pathologically diagnosed as ATC.Imaging examination revealed organ and lymph node metastasis.After multiple cycles of chemotherapy and local radiotherapy,the metastases were not relieved and gradually increased in size and new metastases appeared.The patient immediately received immunotherapy combined with targeted therapy.During treatment,immune-related adverse reactions occurred,which were improved after symptomatic treatment,and tolerated by the patient.The OS of the patient was more than 30 mo after immunotherapy combined with targeted therapy.CONCLUSION For metastatic ATC,surgical treatment,radiotherapy and chemotherapy have no significant effect on remission of the disease.However,immunotherapy has made a breakthrough in the treatment of ATC。
基金Supported by Chinese Research Hospital Association,No.Y2019FH-DTCC-SC3。
文摘BACKGROUND Neoadjuvant or perioperative chemotherapy combined with surgery can reduce postoperative recurrence and improve the long-term survival rate of patients with locally advanced resectable gastric carcinoma.Nivolumab combined with chemotherapy has been recommended by the National Comprehensive Cancer Network guidelines as a first-line therapy for advanced gastric carcinoma/adenocarcinoma of the gastroesophageal junction and serves as the basis for immunotherapy combined with chemotherapy to become a neoadjuvant therapy.Herein,we report a case in which pathologic complete response was achieved by neoadjuvant administration of toripalimab,Herceptin,and docetaxel,oxaliplatin,calcium folinate,and fluorouracil(FLOT)chemotherapy followed by surgery for human epidermal growth factor receptor 2(HER2)-and programmed deathligand 1(PD-L1)-positive locally advanced gastric carcinoma.We hope that this case will shed some light on neoadjuvant therapy for gastric carcinoma.CASE SUMMARY The patient was diagnosed with locally advanced adenocarcinoma of the cardia.Immunohistochemistry of the baseline tissues suggested that the tissues were HER2-(fluorescent in situ hybridization)and PD-L1-positive(combined positive score=1).The patient underwent surgery following a four-cycle neoadjuvant therapy comprising Herceptin,toripalimab,and FLOT chemotherapy.The postoperative pathological findings showed mild atypical hyperplasia of the local glands with chronic mucosal inflammation(proximal stomach),no clear residual tumor(tumor regression grade 0),no regional lymph node metastasis,and negative upper and lower cut ends.The levels of tumor markers were reduced to normal levels after re-examination.With good postoperative recovery,the four-cycle preoperative chemotherapy was continued at the same dosage as that previously administered.After the treatment,the patient was monitored every 3 mo with a follow-up of 12 mo(4 times).As of February 27,2022,he was in a good condition without disease progression.The clinical trial registration number is E2019401.CONCLUSION There are many ongoing studies on neoadjuvant immunotherapy combined with chemotherapy or radiotherapy;however,most of these studies are phase II studies with small cohorts.According to the results of some current studies,these combined regimens have shown promising results in terms of efficacy and safety.However,the clinical efficacy and safety of the neoadjuvant therapies used in these combined regimens need to be confirmed by additional prospective phase III clinical trials,and further exploration of molecular markers for effective populations is required.
基金Supported by KAKENHI(Grant-in-Aid for Scientific Research),No.18H02883.
文摘Gastrointestinal(GI)cancer remains the deadliest cancer in the world.The current standard treatment for GI cancer focuses on 5-fluorouracil-based chemotherapeutic regimens and surgery,and molecular-targeted therapy is expected to be a more effective and less toxic therapeutic strategy for GI cancer.There is wellestablished evidence for the use of epidermal growth factor receptor-targeted and vascular endothelial growth factor-targeted antibodies,which should routinely be incorporated into treatment strategies for GI cancer.Other potential therapeutic targets involve the PI3K/AKT pathway,tumor growth factor-βpathway,mesenchymal-epithelial transition pathway,WNT pathway,poly(ADP-ribose)polymerase,and immune checkpoints.Many clinical trials assessing the agents of targeted therapy are underway and have presented promising and thoughtprovoking results.With the development of molecular biology techniques,we can identify more targetable molecular alterations in larger patient populations with GI cancer.Targeting these molecules will allow us to reach the goal of precision medicine and improve the outcomes of patients with GI cancer.
文摘Modern therapy of acute myeloid leukemia(AML)began in 1973 with the first report of the successful combination of daunorubicin and cytarabine,which led to complete remission in approximately 45%of patients.Accurate AML diagnosis was dependent on morphology,aided initially only by cytochemistry.Unlike acute lymphoblastic leukemia(ALL),immunophenotyping offered little in the diagnosis of AML,at least during the 1970s and 1980s.The advent of reliable cytogenetics changed the entire prognostic outlook of AML.With karyotypic analysis,different groups of AML could be classified and stratified for various therapies.Unique mutational profiling was a major advance in further categorizing AML patients,aided by the immunophenotypic identification of antigenic markers on the cells.All these advances were occurring as the understanding of the importance of the tumor burden—known as minimal residual disease(MRD)—became crucial for the management of AML patients.The efficacy of MRD has rapidly progressed in the past decade,from a specificity of 103 with immunophenotyping to 104 with polymerase chain reaction(PCR),which is only appropriate for some patients with AML,and finally to 105 or even 106 cells with the extraordinary sensitivity of next-generation sequencing(NGS).All of these advances have promoted the concept of personalized medicine,which has led to the advent of targeted agents that can accurately be used for specific diagnostic subtypes.Responses can be predicted and measured accurately.Such targeted agents have now become a cornerstone in the management of AML,increasing effi-cacy and dramatically reducing toxicity.The focus of this review is on one of the most well-studied targeted agents in AML:the FMS-like tyrosine kinase 3(FLT3)inhibitors,which have impacted the prognostication and therapeutics of AML.This review selectively discusses the FLT3 inhibitors in detail,as a model for the other burgeoning targeted agents that have already been approved,as well as those that are currently in development.
基金Supported by China Academy of Medical Science Innovation Fund for Medical Sciences,CIFMS,No.2021-I2M-1-022-2021-S4.
文摘BACKGROUND Targeted therapy(TT)has resulted in controversial efficacy as first-line treatment for biliary tract cancer(BTC).More efficacy comparisons are required to clarify the overall effects of chemotherapy(CT)combined with TT and CT alone on advanced BTC.AIM To conduct a meta-analysis of the available evidence on the efficacy of CT combined with TT for advanced BTC.METHODS The PubMed,EMBASE,ClinicalTrials,Scopus and Cochrane Library databases were systematically searched for relevant studies published from inception to August 2022.Only randomized clinical trials(RCTs)including comparisons between the combination of gemcitabine-based CT with TT and CT alone as firstline treatment for advanced BTC were eligible(PROSPERO-CRD42022313001).The odds ratios(ORs)for the objective response rate(ORR)and hazard ratios(HRs)for both progression-free survival(PFS)and overall survival(OS)were calculated and analyzed.Subgroup analyses based on different targeted agents,CT regimens and tumor locations were prespecified.RESULTS Nine RCTs with a total of 1361 individuals were included and analyzed.The overall analysis showed a significant improvement in ORR in patients treated with CT+TT compared to those treated with CT alone(OR=1.43,95%CI:1.11-1.86,P=0.007)but no difference in PFS or OS.Similar trends were observed in the subgroup treated with agents targeting epidermal growth factor receptor(OR=1.67,95%CI:1.17-2.37,P=0.004)but not in the subgroups treated with agents targeting vascular endothelial growth factor receptor or mesenchymal-epithelial transition factor.Notably,patients who received a CT regimen of gemcitabine+oxaliplatin in the CT+TT arm had both a higher ORR(OR=1.75,95%CI:1.20-2.56,P=0.004)and longer PFS(HR=0.83,95%CI:0.70-0.99,P=0.03)than those in the CT-only arm.Moreover,patients with cholangiocarcinoma treated with CT+TT had significantly increased ORR and PFS(ORR,OR=2.06,95%CI:1.27-3.35,PFS,HR=0.79,95%CI:0.66-0.94).CONCLUSION CT+TT is a potential first-line treatment for advanced BTC that leads to improved tumor control and survival outcomes,and highlighting the importance of CT regimens and tumor types in the application of TT.
文摘BACKGROUND Apocrine carcinoma of the breast is a special type of invasive ductal carcinoma of the breast that is rare in clinical practice.Neoadjuvant therapy,especially neoadjuvant targeted therapy,has rarely been reported for apocrine carcinoma of the breast.CASE SUMMARY A 63-year-old woman presented with apocrine carcinoma of the left breast underwent core needle biopsy.The patient was diagnosed with apocrine carcinoma by immunohistochemical staining and negative hormone status(estrogen receptor and progesterone receptor)but showed overexpression of human epidermal factor receptor 2(HER-2).Moreover,positive expression of androgen receptor(approximately 60%)and gross cystic disease fluid protein 15 was observed.The patient was treated with neoadjuvant targeted therapy consisting of the TCH regimen(docetaxel,carboplatin area under curve 6 and trastuzumab)every 21 d.The mass in the left breast was significantly reduced,and pain in the breast and left upper arm also improved.CONCLUSION HER-2 positive apocrine carcinoma of the breast can be improved by neoadjuvant chemotherapy combined with targeted therapy.
基金The National Key Research and Development Program of China,No.2019YFC1316000the National High Technology Research and Development Program of China,No.2015AA020405+1 种基金the National Natural Science Foundation of China,No.81672337China Postdoctoral Science Foundation,No.2020M671761.
文摘Although targeted therapies and immunotherapies have been effective againstseveral malignancies, the respective monotherapies are limited by low and/orshort-term responses. Specific inhibitors of oncogenic signaling pathways andtumor-associated angiogenesis can activate the anti-tumor immune responses byincreasing tumor antigen presentation or intratumor T cell infiltration. Additionalinsights into the effects and mechanisms of targeted therapies on the induction ofanti-tumor immunity will facilitate development of rational and effective combinationstrategies that synergize rapid tumor regression and durable response. Inthis review, we have summarized the recent combinations of targeted therapiesand immunotherapies, along with the associated clinical challenges.
基金This study was supported by National Natural Science Foundation of China (81572207)
文摘In recent years, with the deepening of research on the pathogenesis of renal cell carcinoma, anti-VEGF receptor inhibitors and mTOR inhibitors have been produced, making metastatic renal cell carcinoma into the era of targeted therapy. This article analyzes the latest research results at home and abroad. For patients with metastatic renal cell carcinoma, sunitinib and pizopanib are the first choice for targeted drugs. The drug dose starts from the standard dose, and the disease can be increased as appropriate when the disease progresses;When responding, it should be treated or reduced in time. When using an anti-VEGF inhibitor, the patient's blood pressure should be closely monitored. When the patient has high blood sugar or diabetes, anti-VEGF inhibitors should be preferred.
基金funded by the National Natural Science Foundation of China(81873917)。
文摘We report two cases of hepatic encephalopathy caused by molecular targeted drugs after the Transjugular intrahepatic portosystemic shunt(TIPS)procedure in our center.The liver toxicities and anti-angiogenic effects induced by targeted drugs may generate an imbalance in ammonia metabolism,elevating blood ammonia levels.TIPS diverts partial blood supply from the liver,aggravates liver impairment,and shunts ammonia-rich blood from the intestine into the systemic circulation.These may be the mechanisms leading to hepatic encephalopathy caused by molecular targeted drugs following TIPS.When clinicians choose molecular targeted therapy as the second or third targeted therapy for patients who have undergone TIPS,the consequence of drug-induced hepatic encephalopathy should also be considered.
