2025-06-26 ローレンスリバモア国立研究所(LLNL)
As described in a recent paper published by Science, a new cancer drug candidate developed by Lawrence Livermore National Laboratory, BBOT (BridgeBio Oncology Therapeutics) and the Frederick National Laboratory for Cancer Research has demonstrated the ability to block tumor growth without triggering a common and debilitating side effect. (Image: Amanda Levasseur & Garry McLeod/LLNL)
<関連情報>
- https://www.llnl.gov/article/53081/cancer-drug-candidate-developed-using-supercomputing-ai-blocks-tumor-growth-without-toxic-side
- https://www.science.org/doi/10.1126/science.adq2004
BBO-10203はRAS-PI3Kα相互作用を阻害することで、高血糖を引き起こすことなく腫瘍の増殖を抑制する BBO-10203 inhibits tumor growth without inducing hyperglycemia by blocking RAS-PI3Kα interaction
Dhirendra K. Simanshu, Rui Xu, James P. Stice, Daniel J. Czyzyk, […] , and Pedro J. Beltran
Science Published:12 Jun 2025
DOI:https://doi.org/10.1126/science.adq2004
Abstract
BBO-10203 is an orally available drug that covalently and specifically binds to the RAS-binding domain of phosphoinositide 3-kinase α (PI3Kα), preventing its activation by HRAS, NRAS, and KRAS. It inhibited PI3Kα activation in tumors with oncogenic mutations in KRAS or PIK3CA, and in tumors with human epidermal growth factor receptor 2 (HER2) amplification or overexpression. In preclinical models, BBO-10203 caused significant tumor growth inhibition across multiple tumor types and showed enhanced efficacy in combination with inhibitors of cyclin-dependent kinase 4/6 (CDK4/6), estrogen receptor (ER), HER2 and KRAS-G12C mutant, including in tumors harboring mutations in Kelch-like ECH-associated protein 1 (KEAP1) and Serine/Threonine Kinase 11 (STK11). Notably, these antitumor effects occurred without inducing hyperglycemia, as insulin signaling does not depend on RAS-mediated PI3Kα activation to promote glucose uptake.
