Contribution of genetic factors to platinum-based chemotherapy sensitivity and prognosis of non-small cell lung cancer

Publication date: Available online 23 November 2016 Source:Mutation Research/Reviews in Mutation Research Author(s): Cristina Pérez-Ramírez, Marisa Cañadas-Garre, Miguel Ángel Molina, Ana I. Robles, María José Faus-Dáder, Miguel Ángel Calleja-Hernández Although platinum-based chemotherapy remains the standard treatment for advanced NSCLC patients, clinical outcomes are poor and most patients develop high-grade toxicities. Genetic factors, such as single nucleotide polymorphisms (SNPs) involved in platinum pharmacodynamics, metabolism and mechanism of action, may account for inter-individual differences shown in effectiveness and toxicity. Polymorphisms in genes involved in DNA repair and others such as PI3K/PTEN/AKT and TGF-β pathways have been demonstrated to be associated with response, survival and toxicity in advanced NSCLC patients treated with platinum-based chemotherapy. Other cellular processes, like DNA methylation and proliferation have been connected with clinical outcome for platinum-based chemotherapy regimens through folate metabolism and cytokine signaling. The influence of gene polymorphisms in the NER pathway on clinical outcome has been extensively investigated in advanced NSCLC patients treated with platinum-based chemotherapy but contradictory results have been reported. The most recent and thorough meta-analyses have failed to show an association between ERCC1 C118T/C8092A and ERCC5 rs1047768 polymorphisms and response to platinum based ...
Source: Mutation Research Reviews in Mutation Research - Category: Genetics & Stem Cells Source Type: research