Genomics of gallbladder cancer: the case for biomarker-driven clinical trial design

Autor: Paul T. Fanta, Razelle Kurzrock, Kelly A. Shimabukuro, Jason K. Sicklick
Rok vydání: 2016
Předmět:
0301 basic medicine
Oncology
Cancer Research
medicine.medical_treatment
Targeted therapy
Cholangiocarcinoma
0302 clinical medicine
Antineoplastic Combined Chemotherapy Protocols
Molecular Targeted Therapy
Precision Medicine
Cancer
Clinical Trials as Topic
Tumor
Disease Management
Standard of Care
Genomics
Prognosis
Gene Expression Regulation
Neoplastic
medicine.anatomical_structure
Biliary Tract Neoplasms
Treatment Outcome
Research Design
030220 oncology & carcinogenesis
Gallbladder Neoplasms
Signal Transduction
Biotechnology
medicine.medical_specialty
Oncology and Carcinogenesis
Biliary tract cancers
Malignancy
Article
03 medical and health sciences
Rare Diseases
Internal medicine
Biomarkers
Tumor
medicine
Genetics
Humans
Genetic Predisposition to Disease
Oncology & Carcinogenesis
Gallbladder cancer
Neoplastic
business.industry
Gallbladder
Carcinoma
Human Genome
Genetic Variation
medicine.disease
Precision medicine
Biomarker (cell)
Clinical trial
030104 developmental biology
Good Health and Well Being
Gene Expression Regulation
Gallbladder Neoplasm
business
Digestive Diseases
Biomarkers
Zdroj: Cancer metastasis reviews, vol 35, iss 2
Popis: Background and aimsGallbladder carcinoma is a rare, aggressive malignancy of the biliary tract associated with a poor prognosis. Despite the deployment of targeted therapies that have demonstrated marked survival benefits in many tumor types, traditional cytotoxic chemotherapy has remained the mainstay of treatment for unresectable and metastatic gallbladder cancer.MethodsSystematic review of ongoing and prior clinical studies shows a paucity of biomarker-driven therapeutic trials using targeted agents in gallbladder cancer. In fact, over the past 6years, of the 38 therapeutic biliary tract protocols listed on clinicaltrials.gov, only 6 (21%) utilized targeted therapies based upon tumor biomarkers or genomics. Now that we have entered the era of next-generation sequencing and precision medicine, we are beginning to identify common and specific genetic alterations in gallbladder carcinomas.ResultsA review of the literature reveals alterations in ARID1A, BRAF, CDKN2A/B, EGFR, ERBB2-4, HKN-RAS, PIK3CA, PBRM1, and TP53. Given the widespread use of tumor genomic profiling and the fact that most of the aforementioned alterations are pharmacologically tractable, these observations suggest the potential for new therapeutic strategies in this aggressive malignancy.ConclusionsTaken together, further understanding of the genomic landscape of gallbladder cancer coupled with biomarker-driven clinical trials that match therapies to targets are urgently needed.
Databáze: OpenAIRE
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