ErbB polymorphisms: insights and implications for response to targeted cancer therapeutics.

摘要: Advances in high-throughput genomic-scanning have expanded the repertory of genetic variations DNA sequences encoding ErbB tyrosine kinase receptors humans, including single nucleotide polymorphisms (SNPs), polymorphic repetitive elements, microsatellite variations, small-scale insertions and deletions. The family members: EGFR, ErbB2, ErbB3 ErbB4 are established as drivers many aspects tumor initiation progression to metastasis. This knowledge has provided rationales for development an arsenal anti-ErbB therapeutics, ranging from small molecule inhibitors monoclonal antibodies. Anti-ErbB agents becoming cornerstone therapeutics management cancers that overexpress hyperactive variants receptors, particular ErbB2-positive breast cancer non-small cell lung carcinomas. However, their clinical benefit been limited a subset patients due wide heterogeneity drug response despite expression targets, attributed intrinsic (primary) acquired (secondary) resistance. Somatic mutations domains extensively investigated preclinical setting determinants either high sensitivity or resistance therapeutics. In contrast, only scant information is available on impact SNPs, which widespread genes receptor structure activity, predictive values susceptibility. review aims briefly update based recent advances deep sequencing technologies, address challenging issues better understanding functional versus combined SNPs topology, receptor-drug interaction, potential exploiting era stratified targeted discussed.