The quest to overcome resistance to EGFR-targeted therapies in cancer

By C. Chong, P. Jänne. Nature Medicine, 2013

997 citations recorded by the source corpus.

All patients with metastatic lung, colorectal, pancreatic or head and neck cancers who initially benefit from epidermal growth factor receptor (EGFR)-targeted therapies eventually develop resistance. An increasing understanding of the number and complexity of resistance mechanisms highlights the Herculean challenge of killing tumors that are resistant to EGFR inhibitors. Our growing knowledge of resistance pathways provides an opportunity to develop new mechanism-based inhibitors and combination therapies to prevent or overcome therapeutic resistance in tumors. We present a comprehensive review of resistance pathways to EGFR-targeted therapies in lung, colorectal and head and neck cancers and discuss therapeutic strategies that are designed to circumvent resistance.

Subfields: Oncology, Pulmonary and Respiratory Medicine

View Paper: https://www.semanticscholar.org/paper/507991cf7d20d2d61babdd89ac0b3cede031f54b

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In Oncology

J. Engelman

In Pulmonary and Respiratory Medicine

Citations in the corpus

Overcoming EGFR T790M and C797S resistance with mutant-selective allosteric inhibitors (2016, neutral): “163 (4) >10 (2) HaCaT (WT) >10 (2) >10 (1) a ELISA-based assay for phosphorylation of EGFR Y1173; The number of times each experiment was repeated is given in parentheses.”
Co-occurring genomic alterations define major subsets of KRAS - mutant lung adenocarcinoma with distinct biology, immune profiles, and therapeutic vulnerabilities (2015, neutral): “iNtRODUctiON The identification of subsets of lung adenocarcinoma with oncogenic drivers has transformed the treatment of non–small cell lung cancer (NSCLC), particularly for patients whose tumors harbor activating mutations in EGFR or oncogenic fusions involving the ALK, RET, and ROS1 kinases (1, 2”
Tumor cell biodiversity drives microenvironmental reprogramming in liver cancer (2019, background): “This phenomenon is not unique to iCCA but a universal feature for most, if not all, solid tumors that have a complex molecular composition (Blakely et al., 2017; Chong and Janne, 2013).”
New horizons in tumor microenvironment biology: challenges and opportunities (2015, background): “Erlotinib and gefitinib Metastatic lung, colorectal, pancreatic, or head and neck cancers Inhibits the epidermal growth factor receptor (EGFR), can stimulate apoptosis and differentiation of cancer cell that lack EGFR Substantial stroma-induced resistance; clinical responses to EGFR tyrosine kinase ”
Current Challenges in Cancer Treatment. (2016, background): “Actually, the genetic basis and some clinically relevant mechanisms of acquired resistance in EGFR- or ALK-mutant lung cancers have been characterized, enabling the development of selective drugs to overcome resistant clones.53 This has been done either by studying clinical samples (re-biopsies take”
Patient-derived Models of Acquired Resistance Can Identify Effective Drug Combinations for Cancer (2014, background): “mechanisms, usually within 1–2 years [EGFR inhibitors reviewed in (6) and ALK inhibitors in (7–9)].”