Nature Communications (Nov 2019)
Targeting melanoma’s MCL1 bias unleashes the apoptotic potential of BRAF and ERK1/2 pathway inhibitors
- Matthew J. Sale,
- Emma Minihane,
- Noel R. Monks,
- Rebecca Gilley,
- Frances M. Richards,
- Kevin P. Schifferli,
- Courtney L. Andersen,
- Emma J. Davies,
- Mario Aladren Vicente,
- Eiko Ozono,
- Aleksandra Markovets,
- Jonathan R. Dry,
- Lisa Drew,
- Vikki Flemington,
- Theresa Proia,
- Duncan I. Jodrell,
- Paul D. Smith,
- Simon J. Cook
Affiliations
- Matthew J. Sale
- Signalling Programme, The Babraham Institute, Babraham Research Campus
- Emma Minihane
- Signalling Programme, The Babraham Institute, Babraham Research Campus
- Noel R. Monks
- Oncology R&D, AstraZeneca
- Rebecca Gilley
- Signalling Programme, The Babraham Institute, Babraham Research Campus
- Frances M. Richards
- Pharmacology and Drug Development Group, Cancer Research UK Cambridge Institute, University of Cambridge, Li Ka Shing Centre
- Kevin P. Schifferli
- Oncology R&D, AstraZeneca
- Courtney L. Andersen
- Oncology R&D, AstraZeneca
- Emma J. Davies
- Oncology R&D, AstraZeneca, Cancer Research UK Cambridge Institute, University of Cambridge, Li Ka Shing Centre
- Mario Aladren Vicente
- CRUK Therapeutic Discovery Laboratories, Jonas Webb Building, Babraham Research Campus
- Eiko Ozono
- Signalling Programme, The Babraham Institute, Babraham Research Campus
- Aleksandra Markovets
- Oncology R&D, AstraZeneca
- Jonathan R. Dry
- Oncology R&D, AstraZeneca
- Lisa Drew
- Oncology R&D, AstraZeneca
- Vikki Flemington
- Oncology R&D, AstraZeneca, Cancer Research UK Cambridge Institute, University of Cambridge, Li Ka Shing Centre
- Theresa Proia
- Oncology R&D, AstraZeneca
- Duncan I. Jodrell
- Pharmacology and Drug Development Group, Cancer Research UK Cambridge Institute, University of Cambridge, Li Ka Shing Centre
- Paul D. Smith
- Oncology R&D, AstraZeneca, Cancer Research UK Cambridge Institute, University of Cambridge, Li Ka Shing Centre
- Simon J. Cook
- Signalling Programme, The Babraham Institute, Babraham Research Campus
- DOI
- https://doi.org/10.1038/s41467-019-12409-w
- Journal volume & issue
-
Vol. 10,
no. 1
pp. 1 – 19
Abstract
BRAF or MEK1/2 inhibitors are cytostatic in melanoma and the surviving cells develop drug resistance. This study shows that the pro-survival pool is biased towards MCL1 in melanoma so that BRAF or MEK1/2 inhibitors are synthetic lethal with the MCL1 inhibitor AZD5991, improving tumour growth inhibition.
