Hepatocellular carcinoma(HCC)is one of the most lethal malignant tumours worldwide.The mortality-to-incidence ratio is up to 91.6%in many countries,representing the third leading cause of cancer-related deaths.Systemi...Hepatocellular carcinoma(HCC)is one of the most lethal malignant tumours worldwide.The mortality-to-incidence ratio is up to 91.6%in many countries,representing the third leading cause of cancer-related deaths.Systemic drugs,including the multikinase inhibitors sorafenib and lenvatinib,are first-line drugs used in HCC treatment.Unfortunately,these therapies are ineffective in most cases due to late diagnosis and the development of tumour resistance.Thus,novel pharmacological alternatives are urgently needed.For instance,immune checkpoint inhibitors have provided new approaches targeting cells of the immune system.Furthermore,monoclonal antibodies against programmed cell death-1 have shown benefits in HCC patients.In addition,drug combinations,including first-line treatment and immunotherapy,as well as drug repurposing,are promising novel therapeutic alternatives.Here,we review the current and novel pharmacological approaches to fight HCC.Preclinical studies,as well as approved and ongoing clinical trials for liver cancer treatment,are discussed.The pharmacological opportunities analysed here should lead to significant improvement in HCC therapy.展开更多
Latin-America (LATAM) is the second region in gastric cancer incidence;gastric adenocarcinoma (GA) represents 95% of all cases. We provide a mutational landscape of GA highlighting a) germline pathogenic variants asso...Latin-America (LATAM) is the second region in gastric cancer incidence;gastric adenocarcinoma (GA) represents 95% of all cases. We provide a mutational landscape of GA highlighting a) germline pathogenic variants associated with hereditary GA, b) germline risk variants associated with sporadic GA, and c) somatic variants present in sporadic GA in LATAM, and analyze how this landscape can be applied for precision medicine. We found that Brazil, Chile, Colombia, Mexico, Peru, and Venezuela are the countries with more published studies from LATAM explicitly related to GA. Our analysis displayed that different germline pathogenic variants for the CDH1 gene have been identified for hereditary GA in Brazilian, Chilean, Colombian, and Mexican populations. An increased risk of developing somatic GA is associated with the following germline risk variants: IL-4, IL-8, TNF-α, PTGS2, NFKB1, RAF1, KRAS and MAPK1 in Brazilian;IL-10 in Chilean;IL-10 in Colombian;EGFR and ERRB2 in Mexican, TCF7L2 and Chr8q24 in Venezuelan population. The path from mutational landscape to precision medicine requires four development levels: 1) Data compilation, 2) Data analysis and integration, 3) Development and approval of clinical approaches, and 4) Population benefits. Generating local genomic information is the initial padlock to overcome to generate and apply precision medicine.展开更多
Cancer is a major cause of death worldwide.Hepatocellular carcinoma(HCC)is one of the malignancies with the highest mortality-to-incidence ratio(>0.9),and in some countries this value is up to 1.Unfortunately,many ...Cancer is a major cause of death worldwide.Hepatocellular carcinoma(HCC)is one of the malignancies with the highest mortality-to-incidence ratio(>0.9),and in some countries this value is up to 1.Unfortunately,many patients are diagnosed at advanced stages of the disease.Therefore,HCC early markers,as well as novel therapeutic approaches,are urgently needed.HCC is the main type of liver cancer and it is associated with different factors including alcohol use,viral infections,and fatty liver disease.A significant percentage of HCC patients previously had liver cirrhosis.Several ion channels have been proposed as novel potential markers and therapeutic targets for diverse cancers including HCC.Here,we review most of the findings associating ion channel expression with HCC and its etiological factors,as well as some possible pro-tumorigenic mechanisms of action for ion channels in HCC.Novel therapies for HCC treatment and prevention are also discussed.Ion channel targeting offers a plethora of opportunities for HCC prevention,early diagnosis,and therapy that may help to reduce the extremely high mortality-to-incidence ratio of this malignancy.展开更多
Activator protein 1(AP-1)is a family of transcription factors composed of Jun,Fos,activating transcription factor(ATF),and musculoaponeurotic fibrosarcoma(MAF)homodimers and heterodimers that regulate diverse cellular...Activator protein 1(AP-1)is a family of transcription factors composed of Jun,Fos,activating transcription factor(ATF),and musculoaponeurotic fibrosarcoma(MAF)homodimers and heterodimers that regulate diverse cellular processes such as proliferation,apoptosis,differentiation,survival,and migration.Accordingly,AP-1 plays an essential role in several diseases including cancer.During liver cancer development,AP-1 abnormal activation has been implicated from cancer initiation to cancer progression.This review aims to provide a current integrative understanding of the role of AP-1 in liver carcinogenesis and suggests potential settings for its clinical use in diagnosis and treatment.Novel AP-1-based therapeutic approaches deserve further investigation and clinical application for the benefit of liver cancer patients.展开更多
文摘Hepatocellular carcinoma(HCC)is one of the most lethal malignant tumours worldwide.The mortality-to-incidence ratio is up to 91.6%in many countries,representing the third leading cause of cancer-related deaths.Systemic drugs,including the multikinase inhibitors sorafenib and lenvatinib,are first-line drugs used in HCC treatment.Unfortunately,these therapies are ineffective in most cases due to late diagnosis and the development of tumour resistance.Thus,novel pharmacological alternatives are urgently needed.For instance,immune checkpoint inhibitors have provided new approaches targeting cells of the immune system.Furthermore,monoclonal antibodies against programmed cell death-1 have shown benefits in HCC patients.In addition,drug combinations,including first-line treatment and immunotherapy,as well as drug repurposing,are promising novel therapeutic alternatives.Here,we review the current and novel pharmacological approaches to fight HCC.Preclinical studies,as well as approved and ongoing clinical trials for liver cancer treatment,are discussed.The pharmacological opportunities analysed here should lead to significant improvement in HCC therapy.
基金This study was supported by the National Institutes of Health (No. R21ES027087, DP)by CONACYT (Consejo Nacional de Ciencia y Tecnología - México) - FOSISS (Fondo Sectorial de Investigación en Salud y Seguridad Social SS/IMSS/ISSTE-CONACYT) (No. 289503 and A3-S-49533 DP, A3-S-48281 to CMG-C, A3-S-41131 to YS-P).
文摘Latin-America (LATAM) is the second region in gastric cancer incidence;gastric adenocarcinoma (GA) represents 95% of all cases. We provide a mutational landscape of GA highlighting a) germline pathogenic variants associated with hereditary GA, b) germline risk variants associated with sporadic GA, and c) somatic variants present in sporadic GA in LATAM, and analyze how this landscape can be applied for precision medicine. We found that Brazil, Chile, Colombia, Mexico, Peru, and Venezuela are the countries with more published studies from LATAM explicitly related to GA. Our analysis displayed that different germline pathogenic variants for the CDH1 gene have been identified for hereditary GA in Brazilian, Chilean, Colombian, and Mexican populations. An increased risk of developing somatic GA is associated with the following germline risk variants: IL-4, IL-8, TNF-α, PTGS2, NFKB1, RAF1, KRAS and MAPK1 in Brazilian;IL-10 in Chilean;IL-10 in Colombian;EGFR and ERRB2 in Mexican, TCF7L2 and Chr8q24 in Venezuelan population. The path from mutational landscape to precision medicine requires four development levels: 1) Data compilation, 2) Data analysis and integration, 3) Development and approval of clinical approaches, and 4) Population benefits. Generating local genomic information is the initial padlock to overcome to generate and apply precision medicine.
文摘Cancer is a major cause of death worldwide.Hepatocellular carcinoma(HCC)is one of the malignancies with the highest mortality-to-incidence ratio(>0.9),and in some countries this value is up to 1.Unfortunately,many patients are diagnosed at advanced stages of the disease.Therefore,HCC early markers,as well as novel therapeutic approaches,are urgently needed.HCC is the main type of liver cancer and it is associated with different factors including alcohol use,viral infections,and fatty liver disease.A significant percentage of HCC patients previously had liver cirrhosis.Several ion channels have been proposed as novel potential markers and therapeutic targets for diverse cancers including HCC.Here,we review most of the findings associating ion channel expression with HCC and its etiological factors,as well as some possible pro-tumorigenic mechanisms of action for ion channels in HCC.Novel therapies for HCC treatment and prevention are also discussed.Ion channel targeting offers a plethora of opportunities for HCC prevention,early diagnosis,and therapy that may help to reduce the extremely high mortality-to-incidence ratio of this malignancy.
基金Villarruel-Melquiades F received the CONAHCyT fellowship(number 787907)to support her PhD studies.
文摘Activator protein 1(AP-1)is a family of transcription factors composed of Jun,Fos,activating transcription factor(ATF),and musculoaponeurotic fibrosarcoma(MAF)homodimers and heterodimers that regulate diverse cellular processes such as proliferation,apoptosis,differentiation,survival,and migration.Accordingly,AP-1 plays an essential role in several diseases including cancer.During liver cancer development,AP-1 abnormal activation has been implicated from cancer initiation to cancer progression.This review aims to provide a current integrative understanding of the role of AP-1 in liver carcinogenesis and suggests potential settings for its clinical use in diagnosis and treatment.Novel AP-1-based therapeutic approaches deserve further investigation and clinical application for the benefit of liver cancer patients.
