Targeting CRTC2 reverses <i>STK11</i> mutant NSCLC tumor resistance to immunotherapy
-proficient tumors. Mechanistically, the abrogation of the binding between CRTC2 and CREB was sufficient to restore sensitivity to immunotherapy. These findings provide critical insights into the central role of CRTC2 in modulating response to ICB and identify the disruption of CRTC2-CREB interaction as a potential therapeutic approach for this patient population.
Authors
- Giorgio Giacomo Galli (ORCID: https://orcid.org/0000-0002-9401-060X)
- Xingyi Shi (ORCID: https://orcid.org/0000-0001-7487-5764)
- Laurent Laborde
- Laura Holzer
- Jincheng Wu (ORCID: https://orcid.org/0000-0002-9776-479X)
- Cory M. Johannessen (ORCID: https://orcid.org/0000-0002-2618-1036)
- Joel P. Wagner (ORCID: https://orcid.org/0000-0001-6579-2908)
- Claudia Bossen (ORCID: https://orcid.org/0000-0002-1695-4744)
- Stéphane Ferretti
- Carlotta Costa (ORCID: https://orcid.org/0000-0002-1199-2485)
- Millicent Gabriel (ORCID: https://orcid.org/0009-0005-2185-0519)
- Lang Ho Lee (ORCID: https://orcid.org/0000-0002-9684-160X)
- Thanos Mourikis (ORCID: https://orcid.org/0009-0003-8830-3101)
- David A. Ruddy (ORCID: https://orcid.org/0000-0001-8244-5609)
- Federico Oreglia
- Ramona Stump
- Sabina Ciaghi
- Lorraine Villemin
- Dimitri Robay (ORCID: https://orcid.org/0009-0001-4088-044X)
- Haiyan Yu
- Ole Ackermann
Institutions
- Novartis (China) (CN)
- Novartis (Netherlands) (NL)
Publication Details
- Journal
- Proceedings of the National Academy of Sciences
- Published
- 2026-04-22
- DOI
- https://doi.org/10.1073/pnas.2508762123
- Primary Topic
- Lung Cancer Treatments and Mutations
- Type
- article
- Field-Weighted Citation Impact
- 0.00