Epigenetic and Oncogenic Inhibitors Cooperatively Drive Differentiation and Kill KRAS <i>-</i> Mutant Colorectal Cancers
Combined EZH2 and RAS pathway inhibitors kill KRAS-mutant colorectal cancer cells and promote durable tumor regression in vivo. These agents function by cooperatively suppressing the WNT pathway, driving differentiation, and epigenetically reprogramming cells to permit the induction of apoptotic signals, which then kill these more differentiated tumor cells.
Authors
- Karen Cichowski (ORCID: https://orcid.org/0000-0003-3940-3782)
- Sandro Santagata (ORCID: https://orcid.org/0000-0002-7528-9668)
- Kristian Helin (ORCID: https://orcid.org/0000-0003-1975-6097)
- Van T.M. Nguyen (ORCID: https://orcid.org/0000-0002-5898-0043)
- Kaia Mattioli (ORCID: https://orcid.org/0000-0002-4536-9237)
- Naiara Perurena (ORCID: https://orcid.org/0000-0003-0874-3389)
- Lauren K. Brais (ORCID: https://orcid.org/0000-0003-1069-0407)
- Natalie F. Pilla (ORCID: https://orcid.org/0000-0002-9971-3590)
- Nuray Gündüz (ORCID: https://orcid.org/0000-0003-3477-2888)
- Alycia Gardner (ORCID: https://orcid.org/0000-0003-2185-5174)
- Marina Watanabe (ORCID: https://orcid.org/0000-0003-2012-1953)
- Kevin M. Haigis (ORCID: https://orcid.org/0000-0003-1922-4509)
- Patrick Loi (ORCID: https://orcid.org/0000-0001-8476-3803)
- Marios Giannakis (ORCID: https://orcid.org/0000-0001-9012-6982)
- Samantha Fitzgerald (ORCID: https://orcid.org/0000-0001-7676-0645)
- Jia‐Ren Lin (ORCID: https://orcid.org/0000-0003-4702-7705)
- Tamsin R.M. Lannagan (ORCID: https://orcid.org/0000-0002-8206-8898)
- Owen J. Sansom (ORCID: https://orcid.org/0000-0001-9540-3010)
- Olesja Popow (ORCID: https://orcid.org/0000-0002-9683-5971)
- Anjana Krishnan
- Kimmie Ng (ORCID: https://orcid.org/0000-0003-0631-1494)
- Carrie L. Rodriguez (ORCID: https://orcid.org/0000-0002-6796-8054)
- Amy E. Schade (ORCID: https://orcid.org/0000-0002-0342-8251)
- Ewa T. Sicinska (ORCID: https://orcid.org/0000-0003-2564-3478)
- Rachel A. Davis (ORCID: https://orcid.org/0000-0002-0486-5154)
- William Tan
- Yilin Xu (ORCID: https://orcid.org/0009-0002-5696-7475)
Institutions
- Broad Institute (US)
- Brigham and Women's Hospital (US)
- Harvard University (US)
- Institute of Cancer Research (GB)
- Cancer Research UK (GB)
- Institute of Cancer Research (CA)
- Dana-Farber Cancer Institute (US)
- Cancer Research UK Scotland Institute (GB)
- CRUK Lung Cancer Centre of Excellence (GB)
- Center for Systems Biology (US)
- University of Glasgow (GB)
Publication Details
- Journal
- Cancer Discovery
- Published
- 2024-08-09
- DOI
- https://doi.org/10.1158/2159-8290.cd-23-0866
- Citations
- 10
- Primary Topic
- Colorectal Cancer Treatments and Studies
- Type
- article
- Field-Weighted Citation Impact
- 2.83
Funders
- American Cancer Society
- Mark Foundation For Cancer Research
- Cancer Research UK
- National Institutes of Health
- National Cancer Institute