From the Biology of PP2A to the PADs for Therapy of Hematologic Malignancies

Frontiers in Oncology
Maria CicconeDanilo Perrotti

Abstract

Over the past decades, an emerging role of phosphatases in the pathogenesis of hematologic malignancies and solid tumors has been established. The tumor-suppressor protein phosphatase 2A (PP2A) belongs to the serine-threonine phosphatases family and accounts for the majority of serine-threonine phosphatase activity in eukaryotic cells. Numerous studies have shown that inhibition of PP2A expression and/or function may contribute to leukemogenesis in several hematological malignancies. Likewise, overexpression or aberrant expression of physiologic PP2A inhibitory molecules (e.g., SET and its associated SETBP1 and CIP2A) may turn off PP2A function and participate to leukemic progression. The discovery of PP2A as tumor suppressor has prompted the evaluation of the safety and the efficacy of new compounds, which can restore PP2A activity in leukemic cells. Although further studies are needed to better understand how PP2A acts in the intricate phosphatases/kinases cancer network, the results reviewed herein strongly support the development on new PP2A-activating drugs and the immediate introduction of those available into clinical protocols for leukemia patients refractory or resistant to current available therapies.

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Citations

Apr 20, 2016·Frontiers in Oncology·Elena ArriazuMaría D Odero
May 24, 2016·International Journal of Molecular Sciences·Chao FangJianmin Li
Apr 14, 2018·Nature Reviews. Drug Discovery·Christopher J Gerry, Stuart L Schreiber
Jun 13, 2019·Genetics and Molecular Biology·Kulsoom GhiasMumtaz J Khan
Dec 5, 2019·International Journal of Molecular Sciences·Tariq HussainXiangmei Zhou
Oct 18, 2019·Oncotarget·Kurt OstherHenrietta Nittby Redebrandt
Sep 9, 2017·Oncotarget·Nicoletta CoccaroFrancesco Albano
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Jan 14, 2018·Molecular Cancer Research : MCR·Shuhei EnjojiKoichi Sato
Apr 9, 2021·Science Translational Medicine·Julia P VainonenJukka Westermarck

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Methods Mentioned

BETA
exome sequencing
chromosomal aberrations
xenografts

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