The molecular characterization of various cancers has shown that cancers with the same origins,histopathologic diagnoses,and clinical stages can be highly heterogeneous in their genetic and epigenetic alterations that...The molecular characterization of various cancers has shown that cancers with the same origins,histopathologic diagnoses,and clinical stages can be highly heterogeneous in their genetic and epigenetic alterations that cause tumorigenesis.A number of cancer driver genes with functional abnormalities that trigger malignant transformation and that are required for the survival of cancer cells have been identified.Therapeutic agents targeting some of these cancer drivers have been successfully developed,resulting in substantial improvements in clinical symptom amelioration and outcomes in a subset of cancer patients.However,because such therapeutic drugs often benefit only a limited number of patients,the successes of clinical development and applications rely on the ability to identify those patients who are sensitive to the targeted therapies.Thus,biomarkers that can predict treatment responses are critical for the success of precision therapy for cancer patients and of anticancer drug development.This review discusses the molecular heterogeneity of lung cancer pathogenesis;predictive biomarkers for precision medicine in lung cancer therapy with drugs targeting epidermal growth factor receptor(EGFR),anaplastic lymphoma kinase(ALK),c-ros oncogene 1 receptor tyrosine kinase[ROSl),and immune checkpoints;biomarkers associated with resistance to these therapeutics;and approaches to identify predictive biomarkers in anticancer drug development.The identification of predictive biomarkers during anticancer drug development is expected to greatly facilitate such development because it will increase the chance of success or reduce the attrition rate.Additionally,such identification will accelerate the drug approval process by providing effective patient stratification strategies in clinical trials to reduce the sample size required to demonstrate clinical benefits.展开更多
Genetic interactions are functional crosstalk among different genetic loci that lead to phenotypic changes,such as health or viability alterations.A disease or lethal phenotype that results from the combined effects o...Genetic interactions are functional crosstalk among different genetic loci that lead to phenotypic changes,such as health or viability alterations.A disease or lethal phenotype that results from the combined effects of gene mutations at different loci is termed a synthetic sickness or synthetic lethality,respectively.Studies of genetic interaction have provided insight on the relationships among biochemical processes or pathways.Cancer results from genetic interactions and is a major focus of current studies in genetic interactions.Various basic and translational cancer studies have explored the concept of genetic interactions,including studies of the mechanistic characterization of genes,drug discovery,biomarker identification and the rational design of combination therapies.This review discusses the implications of genetic interactions in the development of personalized cancer therapies,the identification of treatment-responsive genes,the delineation of mechanisms of chemoresistance and the rational design of combined therapeutic strategies to overcome drug resistance.展开更多
With advances in genomics,transcriptomics,proteomics,and metabolomics,blooming data have been available for exploring molecular alternations in cancers.Many of these molecular alternations have been investigated as bi...With advances in genomics,transcriptomics,proteomics,and metabolomics,blooming data have been available for exploring molecular alternations in cancers.Many of these molecular alternations have been investigated as biomarkers for cancer diagnosis,prognosis,and precision therapies.It is my privilege to introduce this Special Issue of the Journal of Cancer Metastasis and Treatment,which contains four review articles and four original articles that focus on the topic of biomarker discoveries for cancer diagnosis and precision therapy.展开更多
基金supported in part by the National Institutes of Health Specialized Program of Research Excellence(SPORE)Grant CA070907 developmental awardThe University of Texas MD Anderson Cancer Center support Grant CA-016672+3 种基金endowed funds to The University of Texas MD Anderson Cancer Centerthe Moon Shots Programthe Homer Flower Research Fundthe Goldman Sachs Philanthropy Fund
文摘The molecular characterization of various cancers has shown that cancers with the same origins,histopathologic diagnoses,and clinical stages can be highly heterogeneous in their genetic and epigenetic alterations that cause tumorigenesis.A number of cancer driver genes with functional abnormalities that trigger malignant transformation and that are required for the survival of cancer cells have been identified.Therapeutic agents targeting some of these cancer drivers have been successfully developed,resulting in substantial improvements in clinical symptom amelioration and outcomes in a subset of cancer patients.However,because such therapeutic drugs often benefit only a limited number of patients,the successes of clinical development and applications rely on the ability to identify those patients who are sensitive to the targeted therapies.Thus,biomarkers that can predict treatment responses are critical for the success of precision therapy for cancer patients and of anticancer drug development.This review discusses the molecular heterogeneity of lung cancer pathogenesis;predictive biomarkers for precision medicine in lung cancer therapy with drugs targeting epidermal growth factor receptor(EGFR),anaplastic lymphoma kinase(ALK),c-ros oncogene 1 receptor tyrosine kinase[ROSl),and immune checkpoints;biomarkers associated with resistance to these therapeutics;and approaches to identify predictive biomarkers in anticancer drug development.The identification of predictive biomarkers during anticancer drug development is expected to greatly facilitate such development because it will increase the chance of success or reduce the attrition rate.Additionally,such identification will accelerate the drug approval process by providing effective patient stratification strategies in clinical trials to reduce the sample size required to demonstrate clinical benefits.
文摘Genetic interactions are functional crosstalk among different genetic loci that lead to phenotypic changes,such as health or viability alterations.A disease or lethal phenotype that results from the combined effects of gene mutations at different loci is termed a synthetic sickness or synthetic lethality,respectively.Studies of genetic interaction have provided insight on the relationships among biochemical processes or pathways.Cancer results from genetic interactions and is a major focus of current studies in genetic interactions.Various basic and translational cancer studies have explored the concept of genetic interactions,including studies of the mechanistic characterization of genes,drug discovery,biomarker identification and the rational design of combination therapies.This review discusses the implications of genetic interactions in the development of personalized cancer therapies,the identification of treatment-responsive genes,the delineation of mechanisms of chemoresistance and the rational design of combined therapeutic strategies to overcome drug resistance.
文摘With advances in genomics,transcriptomics,proteomics,and metabolomics,blooming data have been available for exploring molecular alternations in cancers.Many of these molecular alternations have been investigated as biomarkers for cancer diagnosis,prognosis,and precision therapies.It is my privilege to introduce this Special Issue of the Journal of Cancer Metastasis and Treatment,which contains four review articles and four original articles that focus on the topic of biomarker discoveries for cancer diagnosis and precision therapy.
