title: Cancer Drug Resistance: A Brief Overview from a Genetic Viewpoint.
abstract: Cancer drug resistance leading to therapeutic failure in the treatment of many cancers encompasses various mechanisms and may be intrinsic relying on the patient's genetic makeup or be acquired by tumors that are initially sensitive to cancer drugs. All in all, it may be responsible for treatment failure in over 90 % of patients with metastatic cancer. Cancer drug resistance, in particular acquired resistance, may stem from the micro-clonality/micro-genetic heterogeneity of the tumors whereby, among others, the following mechanisms may entail resistance: altered expression of drug influx/efflux transporters in the tumor cells mediating lower drug uptake and/or greater efflux of the drug; altered role of DNA repair and impairment of apoptosis; role of epigenomics/epistasis by methylation, acetylation, and altered levels of microRNAs leading to alterations in upstream or downstream effectors; mutation of drug targets in targeted therapy and alterations in the cell cycle and checkpoints; and tumor microenvironment that are briefly reviewed.
authors.affiliation: Centre for Toxicogenomics and Human Health, Genetics, Oncology and Human Toxicology, NOVA Medical School/Faculdade de Ciências Médicas, Universidade Nova de Lisboa, Rua Câmara Pestana 6, 1150-008, Lisbon, Portugal. jose.rueff@fcm.unl.pt.
authors.forename: José
authors.initials: J
authors.lastname: Rueff
authors.affiliation: Centre for Toxicogenomics and Human Health, Genetics, Oncology and Human Toxicology, NOVA Medical School/Faculdade de Ciências Médicas, Universidade Nova de Lisboa, Rua Câmara Pestana 6, 1150-008, Lisbon, Portugal.
authors.forename: António Sebastião
authors.initials: AS
authors.lastname: Rodrigues
mesh_terms: D004260:DNA Repair / Q000187:drug effects; D019008:Drug Resistance, Neoplasm / Q000235:genetics*; D057890:Epigenomics; D006801:Humans; D009369:Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D010597:Pharmacogenetics; D059016:Tumor Microenvironment / Q000187:drug effects / Q000235:genetics
keywords: Acquired resistance and adaptive compensatory pathways; Acquired resistance and tumor micro-heterogeneity; DNA repair and resistance; Epigenomics and resistance; Intrinsic resistance and pharmacogenetics; Tumor microenvironment and resistance; Uptake and efflux transporters in resistance