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在晚期非小细胞肺癌中肿瘤异质性和 EGFR 靶向治疗耐药性：挑战与前景

 

Authors Cheng X, Chen H

Published Date September 2014 Volume 2014:7 Pages 1689—1704

DOI http://dx.doi.org/10.2147/OTT.S66502

Received 21 April 2014, Accepted 26 June 2014, Published 23 September 2014

Abstract: Lung cancer, mostly nonsmall cell lung cancer, continues to be the leading cause of cancer-related death worldwide. With the development of tyrosine kinase inhibitors that selectively target lung cancer-related epidermal growth factor receptor mutations, management of advanced nonsmall cell lung cancer has been greatly transformed. Improvements in progression-free survival and life quality of the patients were observed in numerous clinical studies. However, overall survival is not prolonged because of later-acquired drug resistance. Recent studies reveal a heterogeneous subclonal architecture of lung cancer, so it is speculated that the tumor may rapidly adapt to environmental changes via a Darwinian selection mechanism. In this review, we aim to provide an overview of both spatial and temporal tumor heterogeneity as potential mechanisms underlying epidermal growth factor receptor tyrosine kinase inhibitor resistance in nonsmall cell lung cancer and summarize the possible origins of tumor heterogeneity covering theories of cancer stem cells and clonal evolution, as well as genomic instability and epigenetic aberrations in lung cancer. Moreover, investigational measures that overcome heterogeneity-associated drug resistance and new assays to improve tumor assessment are also discussed.
Keywords: NSCLC, EGFR, TKIs, drug resistance, tumor heterogeneity






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