Universität zu Köln

Tumbrink, Hannah L., Heimsoeth, Alena and Sos, Martin L. (2021). The next tier of EGFR resistance mutations in lung cancer. Oncogene, 40 (1). S. 1 - 12. LONDON: SPRINGERNATURE. ISSN 1476-5594

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Abstract

EGFRmutations account for the majority of druggable targets in lung adenocarcinoma. Over the past decades the optimization of EGFR inhibitors revolutionized the treatment options for patients suffering from this disease. The pace of this development was largely dictated by the inevitable emergence of resistance mutations during drug treatment. As a result, a rapid understanding of the structural and molecular biology of the individual mutations is the key for the development of next-generation inhibitors. Currently, the field faces an unprecedented number of combinations of activating mutations with distinct resistance mutations in parallel to the approval of osimertinib as a first-line drug forEGFR-mutant lung cancer. In this review, we present a survey of the diverse landscape of EGFR resistance mechanisms with a focus on new insights into on-targetEGFRkinase mutations. We discuss array of mutations, their structural effects on the EGFR kinase domain as well as the most promising strategies to overcome the individual resistance profiles found in lung cancer patients.

Item Type:	Journal Article
Creators:	Creators Email ORCID ORCID Put Code Tumbrink, Hannah L. UNSPECIFIED UNSPECIFIED UNSPECIFIED Heimsoeth, Alena UNSPECIFIED UNSPECIFIED UNSPECIFIED Sos, Martin L. UNSPECIFIED UNSPECIFIED UNSPECIFIED
URN:	urn:nbn:de:hbz:38-314929
DOI:	10.1038/s41388-020-01510-w
Journal or Publication Title:	Oncogene
Volume:	40
Number:	1
Page Range:	S. 1 - 12
Date:	2021
Publisher:	SPRINGERNATURE
Place of Publication:	LONDON
ISSN:	1476-5594
Language:	English
Faculty:	Unspecified
Divisions:	Unspecified
Subjects:	no entry
Uncontrolled Keywords:	Keywords Language ACQUIRED-RESISTANCE; ONCOGENIC MUTATIONS; G724S MUTATION; L718Q MUTATION; NSCLC PATIENT; OSIMERTINIB; T790M; INHIBITOR; MECHANISM; AZD9291 Multiple languages Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity Multiple languages
URI:	http://kups.ub.uni-koeln.de/id/eprint/31492