The influence of subclonal resistance mutations on targeted cancer therapy

• Published in: Nature reviews. Clinical oncology Vol. 13; no. 6; pp. 335 - 347
• Main Authors: Schmitt, Michael W., Loeb, Lawrence A., Salk, Jesse J.
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 01.06.2016; Nature Publishing Group
• Subjects: 692/420/2489/68; 692/699/67/1059/2326; 692/699/67/1059/602; 692/699/67/1857; 692/700/565/1436/2185; Cancer; Care and treatment; Drug resistance; Drug Resistance, Neoplasm - genetics; ErbB Receptors - antagonists & inhibitors; Fusion Proteins, bcr-abl - antagonists & inhibitors; Gene mutations; Genes, erbB-1 - genetics; Genetic aspects; Health aspects; Humans; MAP Kinase Kinase Kinases - antagonists & inhibitors; MAP Kinase Kinase Kinases - genetics; MAP Kinase Signaling System - drug effects; Medicine & Public Health; Methods; Molecular targeted therapy; Molecular Targeted Therapy - methods; Mutation - drug effects; Mutation - genetics; Neoplasms - drug therapy; Neoplasms - genetics; Oncology; Protein-Tyrosine Kinases - antagonists & inhibitors; Proto-Oncogene Proteins B-raf - antagonists & inhibitors; Proto-Oncogene Proteins B-raf - genetics; Proto-Oncogene Proteins c-kit - antagonists & inhibitors; review-article

Key Points All cancers probably contain an enormous number of coexisting subclonal mutations; in some cases, every possible mutation could exist in at least one cell in the tumour Resistance to molecularly targeted therapies can arise from selective growth of pre-existing subclones within the bulk o...