Adagrasib in the Treatment of KRAS p.G12C Positive Advanced NSCLC: Design, Development and Place in Therapy

Brian Warnecke,1 Misako Nagasaka1,2 1Department of Medicine, University of California Irvine School of Medicine, Chao Family Comprehensive Cancer Center, Orange, CA, USA; 2Department of Medicine, St. Marianna University School of Medicine, Kawasaki, JapanCorrespondence: Misako Nagasaka, Department o...

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Main Authors: Warnecke B, Nagasaka M
Format: Article
Language:English
Published: Dove Medical Press 2024-12-01
Series:Drug Design, Development and Therapy
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Online Access:https://www.dovepress.com/adagrasib-in-the-treatment-of-kras-pg12c-positive-advanced-nsclc-desig-peer-reviewed-fulltext-article-DDDT
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author Warnecke B
Nagasaka M
author_facet Warnecke B
Nagasaka M
author_sort Warnecke B
collection DOAJ
description Brian Warnecke,1 Misako Nagasaka1,2 1Department of Medicine, University of California Irvine School of Medicine, Chao Family Comprehensive Cancer Center, Orange, CA, USA; 2Department of Medicine, St. Marianna University School of Medicine, Kawasaki, JapanCorrespondence: Misako Nagasaka, Department of Medicine, University of California Irvine School of Medicine, Chao Family Comprehensive Cancer Center, Orange, CA, 92868, USA, Email nagasakm@hs.uci.eduAbstract: One of the most common mutations seen in lung cancers are mutations in Kristen Rat Sarcoma Viral Oncogene Homolog (KRAS), observed in 25– 30% of patients with NSCLC. Mutations in KRAS result in oncogenesis via persistent activation of the MAPK/ERK pathways. Although once thought to be “undruggable”, KRAS p.G12C inhibitors such as sotorasib and adagrasib have been developed. This paper focuses on adagrasib, the second KRAS p.G12C inhibitor to obtain regulatory approval by the FDA and describes the details on its study design, development and current place in therapy.Keywords: Kristen Rat Sarcoma Viral Oncogene Homolog, sotorasib, AMG510, MRTX849, KRYSTAL, CodeBreaK, brain penetration
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series Drug Design, Development and Therapy
spelling doaj-art-0efa164d82a54a04a5e3ddc403c610dd2024-12-05T16:54:29ZengDove Medical PressDrug Design, Development and Therapy1177-88812024-12-01Volume 185673568397983Adagrasib in the Treatment of KRAS p.G12C Positive Advanced NSCLC: Design, Development and Place in TherapyWarnecke BNagasaka MBrian Warnecke,1 Misako Nagasaka1,2 1Department of Medicine, University of California Irvine School of Medicine, Chao Family Comprehensive Cancer Center, Orange, CA, USA; 2Department of Medicine, St. Marianna University School of Medicine, Kawasaki, JapanCorrespondence: Misako Nagasaka, Department of Medicine, University of California Irvine School of Medicine, Chao Family Comprehensive Cancer Center, Orange, CA, 92868, USA, Email nagasakm@hs.uci.eduAbstract: One of the most common mutations seen in lung cancers are mutations in Kristen Rat Sarcoma Viral Oncogene Homolog (KRAS), observed in 25– 30% of patients with NSCLC. Mutations in KRAS result in oncogenesis via persistent activation of the MAPK/ERK pathways. Although once thought to be “undruggable”, KRAS p.G12C inhibitors such as sotorasib and adagrasib have been developed. This paper focuses on adagrasib, the second KRAS p.G12C inhibitor to obtain regulatory approval by the FDA and describes the details on its study design, development and current place in therapy.Keywords: Kristen Rat Sarcoma Viral Oncogene Homolog, sotorasib, AMG510, MRTX849, KRYSTAL, CodeBreaK, brain penetrationhttps://www.dovepress.com/adagrasib-in-the-treatment-of-kras-pg12c-positive-advanced-nsclc-desig-peer-reviewed-fulltext-article-DDDTkristen rat sarcoma viral oncogene homologsotorasibamg510mrtx849krystalcodebreakbrain penetration
spellingShingle Warnecke B
Nagasaka M
Adagrasib in the Treatment of KRAS p.G12C Positive Advanced NSCLC: Design, Development and Place in Therapy
Drug Design, Development and Therapy
kristen rat sarcoma viral oncogene homolog
sotorasib
amg510
mrtx849
krystal
codebreak
brain penetration
title Adagrasib in the Treatment of KRAS p.G12C Positive Advanced NSCLC: Design, Development and Place in Therapy
title_full Adagrasib in the Treatment of KRAS p.G12C Positive Advanced NSCLC: Design, Development and Place in Therapy
title_fullStr Adagrasib in the Treatment of KRAS p.G12C Positive Advanced NSCLC: Design, Development and Place in Therapy
title_full_unstemmed Adagrasib in the Treatment of KRAS p.G12C Positive Advanced NSCLC: Design, Development and Place in Therapy
title_short Adagrasib in the Treatment of KRAS p.G12C Positive Advanced NSCLC: Design, Development and Place in Therapy
title_sort adagrasib in the treatment of kras p g12c positive advanced nsclc design development and place in therapy
topic kristen rat sarcoma viral oncogene homolog
sotorasib
amg510
mrtx849
krystal
codebreak
brain penetration
url https://www.dovepress.com/adagrasib-in-the-treatment-of-kras-pg12c-positive-advanced-nsclc-desig-peer-reviewed-fulltext-article-DDDT
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