KAT5 (Tip60) is a potential therapeutic target in malignant pleural mesothelioma

International Journal of Oncology
Sian CreganSteven G Gray

Abstract

Malignant pleural mesothelioma (MPM) is a rare aggressive cancer of the pleura. Asbestos exposure (through inhalation) is the most well established risk factor for mesothelioma. The current standard of care for patients suffering from MPM is a combination of cisplatin and pemetrexed (or alternatively cisplatin and raltitrexed). Most patients, however, die within 24 months of diagnosis. New therapies are therefore urgently required for this disease. Lysine acetyltransferases (KATs) including KAT5 have been linked with the development of cisplatin resistance. This gene may therefore be altered in MPM and could represent a novel candidate target for intervention. Using RT-PCR screening the expression of all known KAT5 variants was found to be markedly increased in malignant tumors compared to benign pleura. When separated according to histological subtype, KAT5 was significantly overexpressed in both the sarcomatoid and biphasic subgroups for all transcript variants. A panel of MPM cell lines including the normal pleural cells LP9 and Met5A was screened for expression of KAT5 variants. Treatment of cells with a small molecule inhibitor of KAT5 (MG-149) caused significant inhibition of cellular proliferation (p<0.0001), induction o...Continue Reading

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Citations

Nov 8, 2018·Endocrine-related Cancer·Xi WeiBo Xu
Feb 16, 2017·International Journal of Oncology·Sian CreganSteven G Gray
Jan 18, 2019·Stem Cells International·Daniela TrisciuoglioDonatella Del Bufalo
Mar 20, 2018·Journal of Applied Genetics·Ahmed H Ghobashi, Maher A Kamel
Mar 9, 2019·Scientific Reports·A McGuireJ A L Brown
Sep 16, 2020·International Journal of Molecular Sciences·Kah Ni TanCatalina Carrasco-Pozo
Apr 25, 2020·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Kowit HengphasatpornThanyada Rungrotmongkol

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