Impact of single nucleotide polymorphisms on the efficacy and toxicity of egfr tyrosine kinase inhibitors in advanced non-small cell lung cancer patients

Publication date: Available online 9 April 2019Source: Mutation Research/Reviews in Mutation ResearchAuthor(s): Cristina Pérez-Ramírez, Marisa Cañadas-Garre, Miguel Ángel Molina, José Cabeza Barrera, María José Faus-DáderABSTRACTEGFR tyrosine kinase inhibitors (EGFR-TKIs) are the treatment of choice for advanced-stage (IIIB-IV) NSCLC patients with mutations in EGFR. However, EGFR-TKIs clinical outcomes vary from person to person and these inter-individual differences may be due to genetic factors such as single nucleotide polymorphisms (SNPs). SNPs in genes involved in in EGFR-TKIs pharmacodynamics, metabolism and mechanism of action have been demonstrated to be associated with response, survival and toxicity in advanced NSCLC patients treated with EGFR-TKIs.Here we review the influence of gene polymorphisms in the EGFR pathway on clinical outcome and toxicity to EGFR-TKIs in advanced NSCLC patients. The EGFR-216 polymorphism has reported a strong association between response and/or survival to EGFR-TKIs in Caucasian population. Similarly, the effect of EGFR-CA repeats polymorphisms on survival of advanced NSCLC patients treated with EGFR-TKIs have been confirmed both in Caucasian and Asian population. The influence on toxicity of the -216, -191, CA repeats, Arg497Lys and Asp994Asp polymorphisms in EGFR have also been confirmed. Polymorphisms in AKT (rs1130214 and rs1130233) and SMAD3 (rs6494633, rs11071938 and rs11632964) have been associated with survival in advance...
Source: Mutation Research Reviews in Mutation Research - Category: Genetics & Stem Cells Source Type: research