Projects per year
The transcriptional regulator c-MYC is abnormally overexpressed in many human cancers. Evasion from apoptosis is critical for cancer development, particularly c-MYC-driven cancers. We explored which anti-apoptotic BCL-2 family member (expressed under endogenous regulation) is essential to sustain c-MYC-driven lymphoma growth to reveal which should be targeted for cancer therapy. Remarkably, inducible Cre-mediated deletion of even a single Mcl-1 allele substantially impaired the growth of c-MYC-driven mouse lymphomas. Mutations in p53 could diminish but not obviate the dependency of c-MYC-driven mouse lymphomas on MCL-1. Importantly, targeting of MCL-1 killed c-MYC-driven human Burkitt lymphoma cells, even those bearing mutations in p53. Given that loss of one allele of Mcl-1 is well tolerated in healthy tissues, our results suggest that therapeutic targeting of MCL-1 would be an attractive therapeutic strategy for MYC-driven cancers.
|Number of pages||13|
|Journal||Genes & Development|
|Publication status||Published - 1 Jan 2014|
FingerprintDive into the research topics of 'Targeting of MCL-1 kills MYC-driven mouse and human lymphomas even when they bear mutations in p53'. Together they form a unique fingerprint.
- 1 Finished
Epstein-Barr Virus Infections of B Lymphocytes and the Pathogenesis of Virus-Associated Lymphomas
Rickinson, A., Bell, A. & Rowe, M.
1/01/08 → 31/12/12