Despite the advances in surgical techniques, adjuvant chemotherapy and targeted therapy, approximately 40%-70% of patients with progressive colorectal cancer will develop liver metastases, of whom one-third are found ...Despite the advances in surgical techniques, adjuvant chemotherapy and targeted therapy, approximately 40%-70% of patients with progressive colorectal cancer will develop liver metastases, of whom one-third are found at the time of diagnosis.[1] Surgical resection is now the standard treatment and also the only potentially curative treatment for resectable lesions.展开更多
The endoplasmic reticulum(ER),an organelle present in various eukaryotic cells,is responsible for intracellular protein synthesis,post-translational modification,and folding and transport,as well as the regulation of ...The endoplasmic reticulum(ER),an organelle present in various eukaryotic cells,is responsible for intracellular protein synthesis,post-translational modification,and folding and transport,as well as the regulation of lipid and steroid metabolism and Ca2+homeostasis.Hypoxia,nutrient deficiency,and a low pH tumor microenvironment lead to the accumulation of misfolded or unfolded proteins in the ER,thus activating ER stress(ERS)and the unfolded protein response,and resulting in either restoration of cellular homeostasis or cell death.ERS plays a crucial role in cancer oncogenesis,progression,and response to therapies.This article reviews current studies relating ERS to ovarian cancer,the most lethal gynecologic malignancy among women globally,and discusses pharmacological agents and possible targets for therapeutic intervention.展开更多
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 Small cell lung cancer(SCLC)is a common and aggressive subtype of lung cancer.It is characterized by rapid growth and a high mortality rate.Approximately 10%of patients with SCLC present with brain metastas...BACKGROUND Small cell lung cancer(SCLC)is a common and aggressive subtype of lung cancer.It is characterized by rapid growth and a high mortality rate.Approximately 10%of patients with SCLC present with brain metastases at the time of diagnosis,which is associated with a median survival of 5 mo.This study aimed to summarize the effect of bevacizumab on the progression-free survival(PFS)and overall survival of patients with brain metastasis of SCLC.CASE SUMMARY A 62-year-old man was referred to our hospital in February 2023 because of dizziness and numbness of the right lower extremity without headache or fever for more than four weeks.The patient was diagnosed with limited-stage SCLC.He received 8 cycles of chemotherapy combined with maintenance bevacizumab therapy and achieved a PFS of over 7 mo.CONCLUSION The combination of bevacizumab and irinotecan effectively alleviated brain metastasis in SCLC and prolonged PFS.展开更多
Primary liver cancer is one of the most common malignant tumours in the world, and according to statistics, about half of liver cancers occur in China, which seriously threatens the lives and health of people around t...Primary liver cancer is one of the most common malignant tumours in the world, and according to statistics, about half of liver cancers occur in China, which seriously threatens the lives and health of people around the world, especially in China. Hepatocellular carcinoma is the most common type, accounting for about 90 per cent of primary liver cancers. Most patients are asymptomatic in the early stage and fail to pay attention to it. Most of the patients are in the middle or late stage when they are first diagnosed, and only 20% - 30% of them can receive radical hepatectomy. Patients are through the treatment to make the tumour shrinkage and downstaging, to achieve the condition of resectable, that is, the conversion treatment. Conversion therapy has great potential for development and has now become an indispensable treatment for intermediate and advanced hepatocellular carcinoma. However, there are various treatment options for conversion therapy, no uniform guidelines to guide clinical selection, and the overall conversion rate is still low, so it is particularly important to explore appropriate conversion therapy options. This article mainly describes the existing conversion therapies, hoping to provide help and ideas for exploring the best conversion therapies in the future.展开更多
Colorectal cancer(CRC)is the third most diagnosed malignancy and a major leading cause of cancer-related deaths worldwide.Despite advances in therapeutic regimens,the number of patients presenting with metastatic CRC(...Colorectal cancer(CRC)is the third most diagnosed malignancy and a major leading cause of cancer-related deaths worldwide.Despite advances in therapeutic regimens,the number of patients presenting with metastatic CRC(mCRC)is increasing due to resistance to therapy,conferred by a small population of cancer cells,known as cancer stem cells.Targeted therapies have been highly successful in prolonging the overall survival of patients with mCRC.Agents are being developed to target key molecules involved in drug-resistance and metastasis of CRC,and these include vascular endothelial growth factor,epidermal growth factor receptor,human epidermal growth factor receptor-2,mitogen-activated extracellular signal-regulated kinase,in addition to immune checkpoints.Currently,there are several ongoing clinical trials of newly developed targeted agents,which have shown considerable clinical efficacy and have improved the prognosis of patients who do not benefit from conventional chemotherapy.In this review,we highlight recent developments in the use of existing and novel targeted agents against drug-resistant CRC and mCRC.Furthermore,we discuss limitations and challenges associated with targeted therapy and strategies to combat intrinsic and acquired resistance to these therapies,in addition to the importance of implementing better preclinical models and the application of personalized therapy based on predictive biomarkers for treatment selection.展开更多
Background:Hepatocellular carcinoma(HCC)is the sixth most common cancer globally,with limited therapies and unsatisfactory prognosis once in the advanced stages.With promising advances in locoregional and systematic t...Background:Hepatocellular carcinoma(HCC)is the sixth most common cancer globally,with limited therapies and unsatisfactory prognosis once in the advanced stages.With promising advances in locoregional and systematic treatments,fast development of targeted drugs,the success of immunotherapy,as well as the emergence of the therapeutic alliance,conversion therapy has recently become more well developed and an effective therapeutic strategy.This article aimed to review recent developments in conversion therapy in liver transplantation(LT)for HCC.Data sources:We searched for relevant publications on Pub Med before September 2022,using the terms“HCC”,“liver transplantation”,“downstaging”,“bridging treatment”and“conversion therapy.”Results:Conversion therapy was frequently represented as a combination of multiple treatment modalities to downstage HCC and make patients eligible for LT.Although combining various local and systematic treatments in conversion therapy is still controversial,growing evidence has suggested that multimodal combined treatment strategies downstage HCC in a shorter time,which ultimately increases the opportunities for LT.Moreover,the recent breakthrough of immunotherapy and targeted therapy for HCC also benefit patients with advanced-stage tumors.Conclusions:In the era of targeted therapy and immunotherapy,applying the thinking of transplant oncology to benefit HCC patients receiving LT is a new topic that has shed light on advanced-stage patients.With the expansion of conversion therapy concepts,further investigation and research is required to realize the full potential of conversion treatment strategies,including accurately selecting candidates,determining the timing of surgery,improving the conversion rate,and guaranteeing the safety and long-term efficacy of treatment.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
Background:Cholestasis should be relieved by biliary drainage prior to major liver resection.This condition is often associated with bacterial colonization of the otherwise sterile biliary system.Cholangitis reduces t...Background:Cholestasis should be relieved by biliary drainage prior to major liver resection.This condition is often associated with bacterial colonization of the otherwise sterile biliary system.Cholangitis reduces the regenerative capacity of the remaining liver.Therefore,targeted antibiotic therapy is a key feature in perioperative treatment in patients with perihilar cholangiocarcinoma(pCCC).Methods:Between December 1999 and December 2017,251 pCCC patients were treated in our center.In total,115 patients underwent a microbiological analysis.In addition to the characterization of the specific microorganisms and antibiotic resistance,we analyzed subgroups according to preoperative intervention.Results:Enterococci(87/254,34%)and Enterobacteria(65/254,26%)were the most frequently detected genera.In 43%(50/115)of patients,Enterococcus faecalis was found in the bile duct sample.Enterococcus faecium(29/115)and Escherichia coli(29/115)were detected in 25%of patients.In patients with percutaneous transhepatic biliary drainage(3/8,38%)or stents(24/79,30%),Enterococcus faecium was diagnosed most frequently(P<0.05).Enterococcus faecium and Klebsiella oxytoca were significantly more frequently noted in the time period after 2012(P<0.05).With regard to fungal colonization,the focus was on various Candida strains,but these strains generally lacked resistance.Conclusions:pCCC patients exhibit specific bacterial colonization features depending on the type of preoperative biliary intervention.Specifically,targeted antibiosis should be applied in this patient cohort to minimize the risk of biliary complications after major liver resection.In our cohort,the combination of meropenem and vancomycin represents an effective perioperative medical approach.展开更多
Translational therapy refers to a combination of chemotherapy,radiotherapy,targeted therapy,and immunotherapy for patients with advanced gastric cancer who are initially unable to undergo R0 resection.This treatment c...Translational therapy refers to a combination of chemotherapy,radiotherapy,targeted therapy,and immunotherapy for patients with advanced gastric cancer who are initially unable to undergo R0 resection.This treatment can achieve partial or complete remission of the unresectable tumors to meet the criteria for R0 resection,thus enabling the patients to prolong their survival time and improve their quality of life.In gastric cancer,translational therapy has been tried and improved.At present,there are a large number of patients with locally advanced gastric cancer in China,and the selection of suitable patients for transla-tional therapy to prolong objective survival and improve survival quality is one of the hot spots in the field of gastric cancer research.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
Against tumor-dependent metabolic vulnerability is an attractive strategy for tumor-targeted therapy.However,metabolic inhibitors are limited by the drug resistance of cancerous cells due to their metabolic plasticity...Against tumor-dependent metabolic vulnerability is an attractive strategy for tumor-targeted therapy.However,metabolic inhibitors are limited by the drug resistance of cancerous cells due to their metabolic plasticity and heterogeneity.Herein,choline metabolism was discovered by spatially resolved metabolomics analysis as metabolic vulnerability which is highly active in different cancer types,and a choline-modified strategy for small molecule-drug conjugates(SMDCs)design was developed to fool tumor cells into indiscriminately taking in choline-modified chemotherapy drugs for targeted cancer therapy,instead of directly inhibiting choline metabolism.As a proof-of-concept,choline-modified SMDCs were designed,screened,and investigated for their druggability in vitro and in vivo.This strategy improved tumor targeting,preserved tumor inhibition and reduced toxicity of paclitaxel,through targeted drug delivery to tumor by highly expressed choline transporters,and site-specific release by carboxylesterase.This study expands the strategy of targeting metabolic vulnerability and provides new ideas of developing SMDCs for precise cancer therapy.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
Triple-negative breast cancer(TNBC)is a disease with often an aggressive course and a poor prognosis compared to other subtypes of breast cancer.TNBC accounts for approximately 10%–15%of all diagnosed breast cancer c...Triple-negative breast cancer(TNBC)is a disease with often an aggressive course and a poor prognosis compared to other subtypes of breast cancer.TNBC accounts for approximately 10%–15%of all diagnosed breast cancer cases and represents a high unmet need in the field.Up to just a few years ago,chemotherapy was the only systemic treatment option for this subtype(1).To date,TNBC is considered a heterogeneous disease.One of the existing classifications is based on the analysis of mRNA expression in 587 TNBC cases,in which Lehman et al.proposed six subtypes of TNBC as follows:two basal-like(BL1 and BL2)subtypes,a mesenchymal(M)subtype,a mesenchymal stem-like(MSL)subtype,an immunomodulatory(IM)subtype,and a luminal androgen receptor(LAR)subtype(2).Later studies have demonstrated that the IM and MSL subtypes do not correlate with independent subtypes but reflect background expression by dense infiltration of tumor-infiltrating lymphocytes(TILs)or stromal cells.According to this finding,the classification of TNBC has been revised into the following four subtypes:basal 1,basal 2,LAR,and mesenchymal subtypes(3).Over the last years,several new strategies have been investigated for the treatment of patients with TNBC.Among them,immunotherapy,antibody drug conjugates,new chemotherapy agents,and targeted therapy have been and are currently being developed.The present article aims to provide an updated overview on the different treatment options that are now available or are still under investigation for patients with TNBC.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
This article reports a case of massive hepatocellular carcinoma. After intervention combined with targeted and immunotherapy, it was successfully cured by surgical resection, which provides some experience for the com...This article reports a case of massive hepatocellular carcinoma. After intervention combined with targeted and immunotherapy, it was successfully cured by surgical resection, which provides some experience for the comprehensive treatment of liver cancer, and also improves the understanding of systematic treatment of liver cancer, so as to improve the understanding and diagnosis of the disease.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
Pancreatic cancer(PC)remains one of the most challenging diseases,with a very poor 5-year overall survival of around 11.5%.Kirsten rat sarcoma virus(KRAS)mutation is seen in 90%-95%of PC patients and plays an importan...Pancreatic cancer(PC)remains one of the most challenging diseases,with a very poor 5-year overall survival of around 11.5%.Kirsten rat sarcoma virus(KRAS)mutation is seen in 90%-95%of PC patients and plays an important role in cancer cell proliferation,differentiation,metabolism,and survival,making it an essential mutation for targeted therapy.Despite extensive efforts in studying this oncogene,there has been little success in finding a drug to target this pathway,labelling it for decades as“undruggable”.In this article we summarize some of the efforts made to target the KRAS pathway in PC,discuss the challenges,and shed light on promising clinical trials.展开更多
Developing novel cancer therapies that exploit programmed cell death pathways holds promise for advancing cancer treatment.According to a recently published study in Science,copper death(cuproptosis)occurs when intrac...Developing novel cancer therapies that exploit programmed cell death pathways holds promise for advancing cancer treatment.According to a recently published study in Science,copper death(cuproptosis)occurs when intracellular copper is overloaded,triggering aggregation of lipidated mitochondrial proteins and Fe–S cluster proteins.This intriguing phenomenon is triggered by the instability of copper ions.Understanding the molecular mechanisms behind cuproptosis and its associated genes,as identified by Tsvetkov,including ferredoxin 1,lipoic acid synthase,lipoyltransferase 1,dihydrolipid amide dehydrogenase,dihydrolipoamide transacetylase,pyruvate dehydrogenaseα1,pyruvate dehydrogenaseβ,metallothionein,glutaminase,and cyclin-dependent kinase inhibitor 2A,may open new avenues for cancer therapy.Here,we provide a new understanding of the role of copper death and related genes in cancer.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
文摘Despite the advances in surgical techniques, adjuvant chemotherapy and targeted therapy, approximately 40%-70% of patients with progressive colorectal cancer will develop liver metastases, of whom one-third are found at the time of diagnosis.[1] Surgical resection is now the standard treatment and also the only potentially curative treatment for resectable lesions.
基金supported by the National Natural Science Foundation of China(Grant Nos.NSF-82072876 and NSF-82002618)。
文摘The endoplasmic reticulum(ER),an organelle present in various eukaryotic cells,is responsible for intracellular protein synthesis,post-translational modification,and folding and transport,as well as the regulation of lipid and steroid metabolism and Ca2+homeostasis.Hypoxia,nutrient deficiency,and a low pH tumor microenvironment lead to the accumulation of misfolded or unfolded proteins in the ER,thus activating ER stress(ERS)and the unfolded protein response,and resulting in either restoration of cellular homeostasis or cell death.ERS plays a crucial role in cancer oncogenesis,progression,and response to therapies.This article reviews current studies relating ERS to ovarian cancer,the most lethal gynecologic malignancy among women globally,and discusses pharmacological agents and possible targets for therapeutic intervention.
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Yu-Qing Xia Famous Old Chinese Medicine Heritage Workshop of“3+3”Project of Traditional Chinese Medicine Heritage in Beijing,Jing Zhong Yi Ke Zi(2021),No.73National Natural Science Foundation of China,No.81973640+1 种基金Nursery Program of Wangjing Hospital,Chinese Academy of Traditional Chinese Medicine,No.WJYY-YJKT-2022-05China Academy of Traditional Chinese Medicine Wangjing Hospital High-Level Chinese Medicine Hospital Construction Project Chinese Medicine Clinical Evidence-Based Research:The Evidence-Based Research of Electrothermal Acupuncture for Relieving Cancer-Related Fatigue in Patients With Malignant Tumor,No.WYYY-XZKT-2023-20.
文摘BACKGROUND Small cell lung cancer(SCLC)is a common and aggressive subtype of lung cancer.It is characterized by rapid growth and a high mortality rate.Approximately 10%of patients with SCLC present with brain metastases at the time of diagnosis,which is associated with a median survival of 5 mo.This study aimed to summarize the effect of bevacizumab on the progression-free survival(PFS)and overall survival of patients with brain metastasis of SCLC.CASE SUMMARY A 62-year-old man was referred to our hospital in February 2023 because of dizziness and numbness of the right lower extremity without headache or fever for more than four weeks.The patient was diagnosed with limited-stage SCLC.He received 8 cycles of chemotherapy combined with maintenance bevacizumab therapy and achieved a PFS of over 7 mo.CONCLUSION The combination of bevacizumab and irinotecan effectively alleviated brain metastasis in SCLC and prolonged PFS.
文摘Primary liver cancer is one of the most common malignant tumours in the world, and according to statistics, about half of liver cancers occur in China, which seriously threatens the lives and health of people around the world, especially in China. Hepatocellular carcinoma is the most common type, accounting for about 90 per cent of primary liver cancers. Most patients are asymptomatic in the early stage and fail to pay attention to it. Most of the patients are in the middle or late stage when they are first diagnosed, and only 20% - 30% of them can receive radical hepatectomy. Patients are through the treatment to make the tumour shrinkage and downstaging, to achieve the condition of resectable, that is, the conversion treatment. Conversion therapy has great potential for development and has now become an indispensable treatment for intermediate and advanced hepatocellular carcinoma. However, there are various treatment options for conversion therapy, no uniform guidelines to guide clinical selection, and the overall conversion rate is still low, so it is particularly important to explore appropriate conversion therapy options. This article mainly describes the existing conversion therapies, hoping to provide help and ideas for exploring the best conversion therapies in the future.
文摘Colorectal cancer(CRC)is the third most diagnosed malignancy and a major leading cause of cancer-related deaths worldwide.Despite advances in therapeutic regimens,the number of patients presenting with metastatic CRC(mCRC)is increasing due to resistance to therapy,conferred by a small population of cancer cells,known as cancer stem cells.Targeted therapies have been highly successful in prolonging the overall survival of patients with mCRC.Agents are being developed to target key molecules involved in drug-resistance and metastasis of CRC,and these include vascular endothelial growth factor,epidermal growth factor receptor,human epidermal growth factor receptor-2,mitogen-activated extracellular signal-regulated kinase,in addition to immune checkpoints.Currently,there are several ongoing clinical trials of newly developed targeted agents,which have shown considerable clinical efficacy and have improved the prognosis of patients who do not benefit from conventional chemotherapy.In this review,we highlight recent developments in the use of existing and novel targeted agents against drug-resistant CRC and mCRC.Furthermore,we discuss limitations and challenges associated with targeted therapy and strategies to combat intrinsic and acquired resistance to these therapies,in addition to the importance of implementing better preclinical models and the application of personalized therapy based on predictive biomarkers for treatment selection.
基金supported by grants from the National Natural Science Foundation of China(U20A20360)the National Key R&D Program of China(2018YFC1312102)+1 种基金the Development and Reform Commission of Jilin Province(2014G074)the Jilin Provincial Department of Finance(JLSWSRCZX2021-016)。
文摘Background:Hepatocellular carcinoma(HCC)is the sixth most common cancer globally,with limited therapies and unsatisfactory prognosis once in the advanced stages.With promising advances in locoregional and systematic treatments,fast development of targeted drugs,the success of immunotherapy,as well as the emergence of the therapeutic alliance,conversion therapy has recently become more well developed and an effective therapeutic strategy.This article aimed to review recent developments in conversion therapy in liver transplantation(LT)for HCC.Data sources:We searched for relevant publications on Pub Med before September 2022,using the terms“HCC”,“liver transplantation”,“downstaging”,“bridging treatment”and“conversion therapy.”Results:Conversion therapy was frequently represented as a combination of multiple treatment modalities to downstage HCC and make patients eligible for LT.Although combining various local and systematic treatments in conversion therapy is still controversial,growing evidence has suggested that multimodal combined treatment strategies downstage HCC in a shorter time,which ultimately increases the opportunities for LT.Moreover,the recent breakthrough of immunotherapy and targeted therapy for HCC also benefit patients with advanced-stage tumors.Conclusions:In the era of targeted therapy and immunotherapy,applying the thinking of transplant oncology to benefit HCC patients receiving LT is a new topic that has shed light on advanced-stage patients.With the expansion of conversion therapy concepts,further investigation and research is required to realize the full potential of conversion treatment strategies,including accurately selecting candidates,determining the timing of surgery,improving the conversion rate,and guaranteeing the safety and long-term efficacy of treatment.
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.
文摘Background:Cholestasis should be relieved by biliary drainage prior to major liver resection.This condition is often associated with bacterial colonization of the otherwise sterile biliary system.Cholangitis reduces the regenerative capacity of the remaining liver.Therefore,targeted antibiotic therapy is a key feature in perioperative treatment in patients with perihilar cholangiocarcinoma(pCCC).Methods:Between December 1999 and December 2017,251 pCCC patients were treated in our center.In total,115 patients underwent a microbiological analysis.In addition to the characterization of the specific microorganisms and antibiotic resistance,we analyzed subgroups according to preoperative intervention.Results:Enterococci(87/254,34%)and Enterobacteria(65/254,26%)were the most frequently detected genera.In 43%(50/115)of patients,Enterococcus faecalis was found in the bile duct sample.Enterococcus faecium(29/115)and Escherichia coli(29/115)were detected in 25%of patients.In patients with percutaneous transhepatic biliary drainage(3/8,38%)or stents(24/79,30%),Enterococcus faecium was diagnosed most frequently(P<0.05).Enterococcus faecium and Klebsiella oxytoca were significantly more frequently noted in the time period after 2012(P<0.05).With regard to fungal colonization,the focus was on various Candida strains,but these strains generally lacked resistance.Conclusions:pCCC patients exhibit specific bacterial colonization features depending on the type of preoperative biliary intervention.Specifically,targeted antibiosis should be applied in this patient cohort to minimize the risk of biliary complications after major liver resection.In our cohort,the combination of meropenem and vancomycin represents an effective perioperative medical approach.
文摘Translational therapy refers to a combination of chemotherapy,radiotherapy,targeted therapy,and immunotherapy for patients with advanced gastric cancer who are initially unable to undergo R0 resection.This treatment can achieve partial or complete remission of the unresectable tumors to meet the criteria for R0 resection,thus enabling the patients to prolong their survival time and improve their quality of life.In gastric cancer,translational therapy has been tried and improved.At present,there are a large number of patients with locally advanced gastric cancer in China,and the selection of suitable patients for transla-tional therapy to prolong objective survival and improve survival quality is one of the hot spots in the field of gastric cancer research.
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 Natural Science Foundation of China(Grant Nos.:81974500,81773678)the CAMS Innovation Fund for Medical Sciences(Grant No.:2022-I2M-2-001).
文摘Against tumor-dependent metabolic vulnerability is an attractive strategy for tumor-targeted therapy.However,metabolic inhibitors are limited by the drug resistance of cancerous cells due to their metabolic plasticity and heterogeneity.Herein,choline metabolism was discovered by spatially resolved metabolomics analysis as metabolic vulnerability which is highly active in different cancer types,and a choline-modified strategy for small molecule-drug conjugates(SMDCs)design was developed to fool tumor cells into indiscriminately taking in choline-modified chemotherapy drugs for targeted cancer therapy,instead of directly inhibiting choline metabolism.As a proof-of-concept,choline-modified SMDCs were designed,screened,and investigated for their druggability in vitro and in vivo.This strategy improved tumor targeting,preserved tumor inhibition and reduced toxicity of paclitaxel,through targeted drug delivery to tumor by highly expressed choline transporters,and site-specific release by carboxylesterase.This study expands the strategy of targeting metabolic vulnerability and provides new ideas of developing SMDCs for precise cancer therapy.
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Triple-negative breast cancer(TNBC)is a disease with often an aggressive course and a poor prognosis compared to other subtypes of breast cancer.TNBC accounts for approximately 10%–15%of all diagnosed breast cancer cases and represents a high unmet need in the field.Up to just a few years ago,chemotherapy was the only systemic treatment option for this subtype(1).To date,TNBC is considered a heterogeneous disease.One of the existing classifications is based on the analysis of mRNA expression in 587 TNBC cases,in which Lehman et al.proposed six subtypes of TNBC as follows:two basal-like(BL1 and BL2)subtypes,a mesenchymal(M)subtype,a mesenchymal stem-like(MSL)subtype,an immunomodulatory(IM)subtype,and a luminal androgen receptor(LAR)subtype(2).Later studies have demonstrated that the IM and MSL subtypes do not correlate with independent subtypes but reflect background expression by dense infiltration of tumor-infiltrating lymphocytes(TILs)or stromal cells.According to this finding,the classification of TNBC has been revised into the following four subtypes:basal 1,basal 2,LAR,and mesenchymal subtypes(3).Over the last years,several new strategies have been investigated for the treatment of patients with TNBC.Among them,immunotherapy,antibody drug conjugates,new chemotherapy agents,and targeted therapy have been and are currently being developed.The present article aims to provide an updated overview on the different treatment options that are now available or are still under investigation for patients with TNBC.
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This article reports a case of massive hepatocellular carcinoma. After intervention combined with targeted and immunotherapy, it was successfully cured by surgical resection, which provides some experience for the comprehensive treatment of liver cancer, and also improves the understanding of systematic treatment of liver cancer, so as to improve the understanding and diagnosis of the disease.
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.
文摘Pancreatic cancer(PC)remains one of the most challenging diseases,with a very poor 5-year overall survival of around 11.5%.Kirsten rat sarcoma virus(KRAS)mutation is seen in 90%-95%of PC patients and plays an important role in cancer cell proliferation,differentiation,metabolism,and survival,making it an essential mutation for targeted therapy.Despite extensive efforts in studying this oncogene,there has been little success in finding a drug to target this pathway,labelling it for decades as“undruggable”.In this article we summarize some of the efforts made to target the KRAS pathway in PC,discuss the challenges,and shed light on promising clinical trials.
基金Supported by Scientific Research Project of Hunan Education Department,No.21A0054.
文摘Developing novel cancer therapies that exploit programmed cell death pathways holds promise for advancing cancer treatment.According to a recently published study in Science,copper death(cuproptosis)occurs when intracellular copper is overloaded,triggering aggregation of lipidated mitochondrial proteins and Fe–S cluster proteins.This intriguing phenomenon is triggered by the instability of copper ions.Understanding the molecular mechanisms behind cuproptosis and its associated genes,as identified by Tsvetkov,including ferredoxin 1,lipoic acid synthase,lipoyltransferase 1,dihydrolipid amide dehydrogenase,dihydrolipoamide transacetylase,pyruvate dehydrogenaseα1,pyruvate dehydrogenaseβ,metallothionein,glutaminase,and cyclin-dependent kinase inhibitor 2A,may open new avenues for cancer therapy.Here,we provide a new understanding of the role of copper death and related genes in cancer.
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.
