A RAS(ON) Multi-Selective Inhibitor Combination Therapy Triggers Long-term Tumor Control through Senescence-Associated Tumor-Immune Equilibrium in Pancreatic Ductal Adenocarcinoma
Our preclinical studies highlight an opportunity to exploit the senescence program and CD4 T cell-mediated mechanisms to achieve long-term tumor-immune equilibrium and control with RAS-targeted therapies. This work advances our understanding of therapy-induced senescence and suggests new avenues for combination therapies with the potential to benefit patients with PDAC. See related commentary by Lasse Opsahl and Pasca di Magliano, p. 1537.
Authors
- Elisa de Stanchina (ORCID: https://orcid.org/0000-0002-3873-315X)
- Eric Chan (ORCID: https://orcid.org/0009-0002-2835-3994)
- Amanda Kulick (ORCID: https://orcid.org/0000-0001-7365-4142)
- Scott W. Lowe (ORCID: https://orcid.org/0000-0002-5284-9650)
- Ximo Pechuan-Jorge (ORCID: https://orcid.org/0000-0001-8938-7931)
- Almudena Chaves Perez (ORCID: https://orcid.org/0000-0002-2663-4672)
- Exequiel M. Sisso
- Aveline A. Filliol (ORCID: https://orcid.org/0000-0002-1345-8147)
- Eric Rosiek (ORCID: https://orcid.org/0000-0001-6355-1457)
- Jingjing Jiang (ORCID: https://orcid.org/0009-0004-2766-025X)
- Andrea Schietinger (ORCID: https://orcid.org/0000-0003-3644-1687)
- Mallika Singh (ORCID: https://orcid.org/0009-0003-0234-1589)
- Riccardo Mezzadra (ORCID: https://orcid.org/0000-0002-7737-8461)
- Yu-Jui Ho (ORCID: https://orcid.org/0000-0002-7540-024X)
- Ronan Chaligné (ORCID: https://orcid.org/0000-0003-4332-3291)
- Janelle Simon
- Lingyan Jiang (ORCID: https://orcid.org/0009-0006-7523-6968)
- Caroline Broderick (ORCID: https://orcid.org/0000-0001-5733-8625)
- Rashi Raghulan
- Felix Mbuga (ORCID: https://orcid.org/0009-0002-0542-9669)
Institutions
- Memorial Sloan Kettering Cancer Center (US)
- Howard Hughes Medical Institute (US)
- Cornell University (US)
- Revolution Medicines (United States) (US)
Publication Details
- Journal
- Cancer Discovery
- Published
- 2025-04-29
- DOI
- https://doi.org/10.1158/2159-8290.cd-24-1425
- Citations
- 10
- Primary Topic
- Cancer Immunotherapy and Biomarkers
- Type
- article
- Field-Weighted Citation Impact
- 10.45
Funders
- Cancer Research Institute
- Memorial Sloan-Kettering Cancer Center
- Break Through Cancer
- Revolution Medicines
- Nederlandse Organisatie voor Wetenschappelijk Onderzoek
- National Institutes of Health