Data from Mobocertinib (TAK-788): A Targeted Inhibitor of <i>EGFR</i> Exon 20 Insertion Mutants in Non–Small Cell Lung Cancer Article Swipe
Francois Gonzalvez
,
Sylvie Vincent
,
Theresa E. Baker
,
Alexandra E. Gould
,
Shuai Li
,
Scott Wardwell
,
Sara Nadworny
,
Yaoyu Ning
,
Sen Zhang
,
Wei‐Sheng Huang
,
Yongbo Hu
,
Feng Li
,
Matthew T. Greenfield
,
Stephan G. Zech
,
Biplab Das
,
Narayana I. Narasimhan
,
Tim Clackson
,
David C. Dalgarno
,
William C. Shakespeare
,
Michael Fitzgerald
,
Johara Chouitar
,
Robert Griffin
,
Shengwu Liu
,
Kwok‐Kin Wong
,
Xiaotian Zhu
,
Victor M. Rivera
·
YOU?
·
· 2023
· Open Access
·
· DOI: https://doi.org/10.1158/2159-8290.c.6549370.v1
YOU?
·
· 2023
· Open Access
·
· DOI: https://doi.org/10.1158/2159-8290.c.6549370.v1
Most EGFR exon 20 insertion (EGFRex20ins) driver mutations in non–small cell lung cancer (NSCLC) are insensitive to approved EGFR tyrosine kinase inhibitors (TKI). To address the limitations of existing therapies targeting EGFR-mutated NSCLC, mobocertinib (TAK-788), a novel irreversible EGFR TKI, was specifically designed to potently inhibit oncogenic variants containing activating EGFRex20ins mutations with selectivity over wild-type EGFR. The in vitro and in vivo activity of mobocertinib was evaluated in engineered and patient-derived models harboring diverse EGFRex20ins mutations. Mobocertinib inhibited viability of various EGFRex20ins-driven cell lines more potently than approved EGFR TKIs and demonstrated in vivo antitumor efficacy in patient-derived xenografts and murine orthotopic models. These findings support the ongoing clinical development of mobocertinib for the treatment of EGFRex20ins-mutated NSCLC.Significance:No oral EGFR-targeted therapies are approved for EGFR exon 20 insertion (EGFRex20ins) mutation-driven NSCLC. Mobocertinib is a novel small-molecule EGFR inhibitor specifically designed to target EGFRex20ins mutants. Preclinical data reported here support the clinical development of mobocertinib in patients with NSCLC with EGFR exon 20 insertion mutations.See related commentary by Pacheco, p. 1617.This article is highlighted in the In This Issue feature, p. 1601
Related Topics
Concepts
Cancer research
Lung cancer
In vivo
Exon
Erlotinib
Gefitinib
Epidermal growth factor receptor
Tyrosine-kinase inhibitor
Medicine
EGFR inhibitors
Cancer
Chemistry
Biology
Internal medicine
Gene
Genetics
Biochemistry
Metadata
- Type
- preprint
- Language
- en
- Landing Page
- https://doi.org/10.1158/2159-8290.c.6549370.v1
- OA Status
- gold
- References
- 34
- Related Works
- 10
- OpenAlex ID
- https://openalex.org/W4362546506
All OpenAlex metadata
Raw OpenAlex JSON
- OpenAlex ID
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https://openalex.org/W4362546506Canonical identifier for this work in OpenAlex
- DOI
-
https://doi.org/10.1158/2159-8290.c.6549370.v1Digital Object Identifier
- Title
-
Data from Mobocertinib (TAK-788): A Targeted Inhibitor of <i>EGFR</i> Exon 20 Insertion Mutants in Non–Small Cell Lung CancerWork title
- Type
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preprintOpenAlex work type
- Language
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enPrimary language
- Publication year
-
2023Year of publication
- Publication date
-
2023-04-03Full publication date if available
- Authors
-
Francois Gonzalvez, Sylvie Vincent, Theresa E. Baker, Alexandra E. Gould, Shuai Li, Scott Wardwell, Sara Nadworny, Yaoyu Ning, Sen Zhang, Wei‐Sheng Huang, Yongbo Hu, Feng Li, Matthew T. Greenfield, Stephan G. Zech, Biplab Das, Narayana I. Narasimhan, Tim Clackson, David C. Dalgarno, William C. Shakespeare, Michael Fitzgerald, Johara Chouitar, Robert Griffin, Shengwu Liu, Kwok‐Kin Wong, Xiaotian Zhu, Victor M. RiveraList of authors in order
- Landing page
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https://doi.org/10.1158/2159-8290.c.6549370.v1Publisher landing page
- Open access
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YesWhether a free full text is available
- OA status
-
goldOpen access status per OpenAlex
- OA URL
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https://doi.org/10.1158/2159-8290.c.6549370.v1Direct OA link when available
- Concepts
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Cancer research, Lung cancer, In vivo, Exon, Erlotinib, Gefitinib, Epidermal growth factor receptor, Tyrosine-kinase inhibitor, Medicine, EGFR inhibitors, Cancer, Chemistry, Biology, Internal medicine, Gene, Genetics, BiochemistryTop concepts (fields/topics) attached by OpenAlex
- Cited by
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0Total citation count in OpenAlex
- References (count)
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34Number of works referenced by this work
- Related works (count)
-
10Other works algorithmically related by OpenAlex
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| referenced_works | https://openalex.org/W2995866033, https://openalex.org/W2946040207, https://openalex.org/W1967394241, https://openalex.org/W2903556107, https://openalex.org/W2961016476, https://openalex.org/W2129787264, https://openalex.org/W2891758514, https://openalex.org/W2027834197, https://openalex.org/W2145497412, https://openalex.org/W2129360604, https://openalex.org/W2995864319, https://openalex.org/W2139804581, https://openalex.org/W3217485783, https://openalex.org/W2011513069, https://openalex.org/W2040299716, https://openalex.org/W2801651204, https://openalex.org/W2793873799, https://openalex.org/W177903961, https://openalex.org/W2075445339, https://openalex.org/W2170248468, https://openalex.org/W2111662961, https://openalex.org/W2030205108, https://openalex.org/W3024571856, https://openalex.org/W2337836619, https://openalex.org/W2239287815, https://openalex.org/W2133963438, https://openalex.org/W2164613605, https://openalex.org/W2920175805, https://openalex.org/W3089272461, https://openalex.org/W2838798742, https://openalex.org/W2760639821, https://openalex.org/W1566300951, https://openalex.org/W2087277155, https://openalex.org/W2507541911 |
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