Therapeutic strategies utilized in the setting of acquired resistance to EGFR tyrosine kinase inhibitors Journal Article
| Authors: | Yu, H. A.; Riely, G. J.; Lovly, C. M. |
| Article Title: | Therapeutic strategies utilized in the setting of acquired resistance to EGFR tyrosine kinase inhibitors |
| Abstract: | Patients with EGFR-mutant lung cancer derive significant therapeutic benefit from treatment with EGFR tyrosine kinase inhibitors (TKI). Unfortunately, acquired resistance is an inevitable consequence of this treatment strategy, with a broad variety of resistance mechanisms including acquired EGFR mutations (e.g., T790M) and activation of bypass signaling pathways, such as MET and HER2. Several therapeutic strategies hypothesized to delay or overcome resistance have been tested in clinical trials, including "nextgeneration" EGFR TKIs and rational combinations of targeted agents. However, to date, there are no FDAapproved therapies for patients with acquired resistance to first-line EGFR TKI therapy. There remains a critical need for more effective and better tailored treatments in this setting to match treatments to the individual patient and specific resistance mechanism at hand. In this review, we discuss known mechanisms of resistance to first-line EGFR TKI therapy and describe previous and ongoing strategies to overcome resistance. |
| Keywords: | epidermal growth factor; unclassified drug; review; bevacizumab; erlotinib; cancer growth; diarrhea; paclitaxel; antineoplastic agent; gene targeting; carboplatin; unindexed drug; progression free survival; phase 2 clinical trial; lung cancer; cetuximab; protein tyrosine kinase inhibitor; hyperglycemia; rash; gefitinib; hydroxychloroquine; phase 3 clinical trial; phase 1 clinical trial; trastuzumab; everolimus; neratinib; non small cell lung cancer; nimotuzumab; fibroblast growth factor receptor; crizotinib; cabozantinib; afatinib; dacomitinib; rilotumumab; human; emibetuzumab; onartuzumab; asp 8273; azd 9291; capmatinib; egf 816; icotinib; rociletinib; [2 [[5 chloro 2 [[4 [4 (dimethylamino) 1 piperidinyl] 2 methoxyphenyl]amino] 4 pyrimidinyl]amino]phenyl]dimethylphosphine oxide |
| Journal Title: | Clinical Cancer Research |
| Volume: | 20 |
| Issue: | 23 |
| ISSN: | 1078-0432 |
| Publisher: | American Association for Cancer Research |
| Date Published: | 2014-12-01 |
| Start Page: | 5898 |
| End Page: | 5907 |
| Language: | English |
| DOI: | 10.1158/1078-0432.ccr-13-2437 |
| PROVIDER: | scopus |
| PMCID: | PMC4253858 |
| PUBMED: | 25303979 |
| DOI/URL: | |
| Notes: | Export Date: 2 January 2015 -- Source: Scopus |
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