Targeting melanoma’s MCL1 bias unleashes the apoptotic potential of BRAF and ERK1/2 pathway inhibitors

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 inhibit...

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Main Authors:	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
Format:	Article
Language:	English
Published:	Nature Publishing Group 2019-11-01
Series:	Nature Communications
Online Access:	https://doi.org/10.1038/s41467-019-12409-w

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spelling	doaj-03dfbb8e162440b8bfec0b14545e606c2021-05-11T11:41:00ZengNature Publishing GroupNature Communications2041-17232019-11-0110111910.1038/s41467-019-12409-wTargeting melanoma’s MCL1 bias unleashes the apoptotic potential of BRAF and ERK1/2 pathway inhibitorsMatthew J. Sale0Emma Minihane1Noel R. Monks2Rebecca Gilley3Frances M. Richards4Kevin P. Schifferli5Courtney L. Andersen6Emma J. Davies7Mario Aladren Vicente8Eiko Ozono9Aleksandra Markovets10Jonathan R. Dry11Lisa Drew12Vikki Flemington13Theresa Proia14Duncan I. Jodrell15Paul D. Smith16Simon J. Cook17Signalling Programme, The Babraham Institute, Babraham Research CampusSignalling Programme, The Babraham Institute, Babraham Research CampusOncology R&D, AstraZenecaSignalling Programme, The Babraham Institute, Babraham Research CampusPharmacology and Drug Development Group, Cancer Research UK Cambridge Institute, University of Cambridge, Li Ka Shing CentreOncology R&D, AstraZenecaOncology R&D, AstraZenecaOncology R&D, AstraZeneca, Cancer Research UK Cambridge Institute, University of Cambridge, Li Ka Shing CentreCRUK Therapeutic Discovery Laboratories, Jonas Webb Building, Babraham Research CampusSignalling Programme, The Babraham Institute, Babraham Research CampusOncology R&D, AstraZenecaOncology R&D, AstraZenecaOncology R&D, AstraZenecaOncology R&D, AstraZeneca, Cancer Research UK Cambridge Institute, University of Cambridge, Li Ka Shing CentreOncology R&D, AstraZenecaPharmacology and Drug Development Group, Cancer Research UK Cambridge Institute, University of Cambridge, Li Ka Shing CentreOncology R&D, AstraZeneca, Cancer Research UK Cambridge Institute, University of Cambridge, Li Ka Shing CentreSignalling Programme, The Babraham Institute, Babraham Research CampusBRAF 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.https://doi.org/10.1038/s41467-019-12409-w
collection	DOAJ
language	English
format	Article
sources	DOAJ
author	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
spellingShingle	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 Targeting melanoma’s MCL1 bias unleashes the apoptotic potential of BRAF and ERK1/2 pathway inhibitors Nature Communications
author_facet	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
author_sort	Matthew J. Sale
title	Targeting melanoma’s MCL1 bias unleashes the apoptotic potential of BRAF and ERK1/2 pathway inhibitors
title_short	Targeting melanoma’s MCL1 bias unleashes the apoptotic potential of BRAF and ERK1/2 pathway inhibitors
title_full	Targeting melanoma’s MCL1 bias unleashes the apoptotic potential of BRAF and ERK1/2 pathway inhibitors
title_fullStr	Targeting melanoma’s MCL1 bias unleashes the apoptotic potential of BRAF and ERK1/2 pathway inhibitors
title_full_unstemmed	Targeting melanoma’s MCL1 bias unleashes the apoptotic potential of BRAF and ERK1/2 pathway inhibitors
title_sort	targeting melanoma’s mcl1 bias unleashes the apoptotic potential of braf and erk1/2 pathway inhibitors
publisher	Nature Publishing Group
series	Nature Communications
issn	2041-1723
publishDate	2019-11-01
description	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.
url	https://doi.org/10.1038/s41467-019-12409-w
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Targeting melanoma’s MCL1 bias unleashes the apoptotic potential of BRAF and ERK1/2 pathway inhibitors

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