Rational, biologically based treatment of EGFR-mutant non-small-cell lung cancer

By William Pao, J. Chmielecki. Nature Reviews. Cancer, 2010

1,084 citations recorded by the source corpus.

Epidermal growth factor receptor (EGFR)-mutant non-small-cell lung cancer (NSCLC) was first recognized in 2004 as a distinct, clinically relevant molecular subset of lung cancer. The disease has been the subject of intensive research at both the basic scientific and clinical levels, becoming a paradigm for how to understand and treat oncogene-driven carcinomas. Although patients with EGFR-mutant tumours have increased sensitivity to tyrosine kinase inhibitors (TKIs), primary and acquired resistance to these agents remains a major clinical problem. This Review summarizes recent developments aimed at treating and ultimately curing the disease.

Subfields: Oncology, Pulmonary and Respiratory Medicine

View Paper: https://www.semanticscholar.org/paper/2996ce2cca947dd56aa34c6ca5d317a304adb5b4

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Citations in the corpus

ERBB receptors: From oncogene discovery to basic science to mechanism-based cancer therapeutics (2014, background): “The causal role of EGFR in tumorigenesis was further solidified in 2004 when somatic, activating mutations in EGFR were discovered in a subset of non-small-cell lung cancers (NSCLCs) (Lynch et al., 2004; Paez et al., 2004; Pao et al., 2004) (Table 1).”
Mapping the hallmarks of lung adenocarcinoma with massively parallel sequencing (2012, background): “…routinely used to guide clinical care of lung adenocarcinoma patients, largely due to clinical trials that demonstrated superior efficacy of targeted kinase inhibitors as compared to standard chemotherapy for patients with EGFR mutations or ALK fusions (Kwak et al., 2010; Pao and Chmielecki, 2010).”
The RAS/RAF/MEK/ERK and the PI3K/AKT signalling pathways: role in cancer pathogenesis and implications for therapeutic approaches (2012, background): “In this regard, several different studies have demonstrated that EGFR and KRAS mutations are mutually exclusive in NSCLC [29].”
Consolidative Radiotherapy for Limited Metastatic Non–Small-Cell Lung Cancer: A Phase 2 Randomized Clinical Trial (2018, methodology): “metastaticNSCLC.(16-26)Single-armphase2 studies incorporating surgery or radiotherapy then showed the benefits of local therapy for synchronous metastatic NSCLC.”
AZD9291, an irreversible EGFR TKI, overcomes T790M-mediated resistance to EGFR inhibitors in lung cancer (2014, neutral): “Mutations in EGFR occur in 10% to 35% of NSCLCs and confer sensitivity to the EGFR TKIs erlotinib, gefitinib, and afatinib (6).”