PERK mediates resistance to BRAF inhibition in melanoma with impaired PTEN

Abstract Targeting mutant BRAF in patients with melanomas harboring this oncogene has been highly successful as a first-line treatment, but other mutations may affect its efficacy and alter the route of acquired resistance resulting in recurrence and poor prognosis. As an evolving strategy, melanoma...

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Autores principales:	Yifei Qin, Qiang Zuo, Lei Huang, Liping Huang, Glenn Merlino, Yanlin Yu
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2021
Materias:	Neoplasms. Tumors. Oncology. Including cancer and carcinogens RC254-282
Acceso en línea:	https://doaj.org/article/296a03e409584af690987eefc1e8c182
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spelling	oai:doaj.org-article:296a03e409584af690987eefc1e8c1822021-12-02T16:17:16ZPERK mediates resistance to BRAF inhibition in melanoma with impaired PTEN10.1038/s41698-021-00207-x2397-768Xhttps://doaj.org/article/296a03e409584af690987eefc1e8c1822021-07-01T00:00:00Zhttps://doi.org/10.1038/s41698-021-00207-xhttps://doaj.org/toc/2397-768XAbstract Targeting mutant BRAF in patients with melanomas harboring this oncogene has been highly successful as a first-line treatment, but other mutations may affect its efficacy and alter the route of acquired resistance resulting in recurrence and poor prognosis. As an evolving strategy, melanoma treatment needs to be expanded to include targets based on newly discovered emerging molecules and pathways. We here show that PERK plays a critical role in BRAF inhibitor-acquired resistance in melanoma with impaired PTEN. Inhibition of PERK by either shRNA or a pharmacological inhibitor blocked the growth of BRAF inhibitor-resistant melanoma with impaired PTEN in vitro and in vivo, suggesting an effective approach against melanomas with mutant BRAF and PTEN deficiency. Our current findings, along with our previous discovery that the AXL/AKT axis mediates resistance to BRAF inhibition in melanoma with wild-type PTEN, provide new insights toward a strategy for combating BRAF inhibition-acquired resistance in BRAF mutant melanoma with different PTEN statuses.Yifei QinQiang ZuoLei HuangLiping HuangGlenn MerlinoYanlin YuNature PortfolioarticleNeoplasms. Tumors. Oncology. Including cancer and carcinogensRC254-282ENnpj Precision Oncology, Vol 5, Iss 1, Pp 1-9 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Neoplasms. Tumors. Oncology. Including cancer and carcinogens RC254-282
spellingShingle	Neoplasms. Tumors. Oncology. Including cancer and carcinogens RC254-282 Yifei Qin Qiang Zuo Lei Huang Liping Huang Glenn Merlino Yanlin Yu PERK mediates resistance to BRAF inhibition in melanoma with impaired PTEN
description	Abstract Targeting mutant BRAF in patients with melanomas harboring this oncogene has been highly successful as a first-line treatment, but other mutations may affect its efficacy and alter the route of acquired resistance resulting in recurrence and poor prognosis. As an evolving strategy, melanoma treatment needs to be expanded to include targets based on newly discovered emerging molecules and pathways. We here show that PERK plays a critical role in BRAF inhibitor-acquired resistance in melanoma with impaired PTEN. Inhibition of PERK by either shRNA or a pharmacological inhibitor blocked the growth of BRAF inhibitor-resistant melanoma with impaired PTEN in vitro and in vivo, suggesting an effective approach against melanomas with mutant BRAF and PTEN deficiency. Our current findings, along with our previous discovery that the AXL/AKT axis mediates resistance to BRAF inhibition in melanoma with wild-type PTEN, provide new insights toward a strategy for combating BRAF inhibition-acquired resistance in BRAF mutant melanoma with different PTEN statuses.
format	article
author	Yifei Qin Qiang Zuo Lei Huang Liping Huang Glenn Merlino Yanlin Yu
author_facet	Yifei Qin Qiang Zuo Lei Huang Liping Huang Glenn Merlino Yanlin Yu
author_sort	Yifei Qin
title	PERK mediates resistance to BRAF inhibition in melanoma with impaired PTEN
title_short	PERK mediates resistance to BRAF inhibition in melanoma with impaired PTEN
title_full	PERK mediates resistance to BRAF inhibition in melanoma with impaired PTEN
title_fullStr	PERK mediates resistance to BRAF inhibition in melanoma with impaired PTEN
title_full_unstemmed	PERK mediates resistance to BRAF inhibition in melanoma with impaired PTEN
title_sort	perk mediates resistance to braf inhibition in melanoma with impaired pten
publisher	Nature Portfolio
publishDate	2021
url	https://doaj.org/article/296a03e409584af690987eefc1e8c182
work_keys_str_mv	AT yifeiqin perkmediatesresistancetobrafinhibitioninmelanomawithimpairedpten AT qiangzuo perkmediatesresistancetobrafinhibitioninmelanomawithimpairedpten AT leihuang perkmediatesresistancetobrafinhibitioninmelanomawithimpairedpten AT lipinghuang perkmediatesresistancetobrafinhibitioninmelanomawithimpairedpten AT glennmerlino perkmediatesresistancetobrafinhibitioninmelanomawithimpairedpten AT yanlinyu perkmediatesresistancetobrafinhibitioninmelanomawithimpairedpten
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PERK mediates resistance to BRAF inhibition in melanoma with impaired PTEN

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