Combination of KRASG12C targeted adagrasib with anti-PD-1 immune-checkpoint inhibitor to improve overall survival and prevent recurrence in preclinical models of brain metastasis
Clicks: 2
ID: 315603
2026
Article Quality & Performance Metrics
Overall Quality
Not rated
Combines reader engagement with the AI quality analysis. This
article has not been analysed, so there is no overall score —
reader engagement is measured and shown alongside.
Reader Engagement
Popular Article
0.3
/100
2 views
1 readers
AI Quality Assessment
Not analyzed
Readership in this journal
PopularRanked #59 of 104 articles by views in Neuro-Oncology Advances
Most read
Least read
Bar heights use a square-root scale.
Mint this article as an NFT
Not yet mintedCreate a permanent, verifiable on-chain record of this article on the Scimatic Network. The NFT is held in your Journament account, and you can withdraw it to your own wallet at any time.
5
SUSD
one-off · no wallet required
Abstract
Abstract BACKGROUND Despite advances in treatment, brain metastasis (BM) management remains a significant challenge. Adagrasib is a brain-penetrant KRASG12C inhibitor active in patients with BM. KRAS mutations are linked with immune escape and may contribute to the limited clinical benefit from single-agent immune checkpoint inhibitors (ICI) targeting PD-1/PD-L1 in BM. Although adagrasib sensitizes extracranial tumors to ICI, its intracranial benefit combined with immunotherapy remains unknown. Here, we evaluate adagrasib with ICI in mouse models that mimic the BM immune microenvironment. METHODS We tested the in vitro efficacy of adagrasib on two KrasG12C-mutant murine cancer cells: colorectal CT26G12C and lung cancer KPARG12C. Murine BM models resembling the immunologic characteristics of BM were established by subcutaneous and intracranial injection of these cells. Animals were treated with adagrasib combined with anti-PD-1 and monitored for intracranial tumor growth and survival. Disease-free mice after 11–13 weeks were rechallenged with a higher tumor cell dose to assess tumor-specific memory. RESULTS Three-week adagrasib monotherapy and combination therapy with ICI demonstrated benefit in colorectal and lung cancer BM models. Adagrasib alone and in combination demonstrated similarly potent anti-tumor effects against extracranial tumors. While monotherapies reduced intracranial tumor growth, adagrasib with ICI showed the most favorable outcome. Although both adagrasib monotherapy and combination therapy extended survival, long-term intracranial disease control after rechallenge was the greatest with combination therapy. CONCLUSIONS Adagrasib with ICI improved long-term survival and blocked CNS progression in dual extra- and intracranial BM models. These findings support investigation of adagrasib with ICI in patients with KRASG12C-mutant BM.
| Reference Key |
openalex_W7163147358
Use this key to autocite in the manuscript while using
SciMatic Manuscript Manager or Thesis Manager
|
|---|---|
| Authors | Consuelo Torrini, Naema Nayyar, Gregory R Wojtkiewicz, Anita Giobbie-Hurder, Magali de Sauvage, Christian Migliarese, Elizabeth J Summers, Nazanin Ijad, Erika Yamazawa, Britney S. Zhang, Emily Sullivan, Varun Sasisekharan, Leland G Richardson, Braxton Marion, Peter Olson, Hiroaki Wakimoto, Priscilla K Brastianos |
| Journal | Neuro-Oncology Advances |
| Year | 2026 |
| DOI |
10.1093/noajnl/vdag107
|
| URL | |
| Keywords | Keywords not found |
Citations
No citations found. To add a citation, contact the admin at info@scimatic.org
Comments
No comments yet. Be the first to comment on this article.