Functional Analysis of Rare <i>RAS</i> Variants of Unknown Significance
This study presents the first comprehensive functional analysis of 298 rare RAS variants, identifying 66 novel oncogenic mutations and 15 KRAS variants sensitive to the noncovalent pan-KRAS inhibitor BI-2865. The heterogeneity in drug responses among KRAS variants underscores the need for variant-specific therapeutic strategies. These findings provide a preclinical framework for guiding personalized treatment in RAS-driven cancers and a valuable resource for understanding the clinical relevance of rare RAS mutations.
Authors
- Soohwan Park
- Kenji Suzuki (ORCID: https://orcid.org/0000-0002-1291-2619)
- Masachika Ikegami (ORCID: https://orcid.org/0000-0003-0491-7142)
- Rina Kitada
- Shinji Kohsaka (ORCID: https://orcid.org/0000-0001-8651-6136)
- Kazuya Takamochi (ORCID: https://orcid.org/0000-0002-1721-6364)
- Hiroyuki Mano (ORCID: https://orcid.org/0000-0003-4645-0181)
Institutions
- Tokyo Metropolitan Komagome Hospital (JP)
- Juntendo University (JP)
- National Cancer Research Institute (GB)
Publication Details
- Journal
- Cancer Research Communications
- Published
- 2025-09-19
- DOI
- https://doi.org/10.1158/2767-9764.crc-25-0188
- Citations
- 1
- Primary Topic
- Protein Kinase Regulation and GTPase Signaling
- Type
- article
- Field-Weighted Citation Impact
- 0.81
Funders
- American Association for Cancer Research
- Japan Agency for Medical Research and Development
- Eisai
- Moonshot Research and Development Program