Advances in Chemical Biology

0502886 - ÚMG 2019 RIV CZ eng M - Monography Chapter
Macůrek, Libor
PPM1D as a driver and pharmacological target in clonal hematopoiesis.
Advances in Chemical Biology. Praha: OPTIO CZ, 2019 - (Bartůněk, P.), s. 32-39. ISBN 978-80-88011-03-3
R&D Projects: GA MŠMT LO1220
Institutional support: RVO:68378050
Keywords : cancer * phosphatase * DNA damage response * inhibitor * clonal hematopoiesis
OECD category: Cell biology

Chemotherapy or radiotherapy cause genotoxic stress that kills cancer cells and ideally only tolerable DNA damage to the neighboring healthy tissues. Cell fate after exposure to genotoxic stress is determined by the tumor suppressor p53 that controls transcription of both pro-survival and pro-apoptotic genes. Depending on the DNA damage load, cells activate the cell cycle checkpoint arrest or die through programmed cell death. Protein phosphatase 2C delta (referred to as WIP1) is a negative regulator of p53 and has been proposed as potential pharmaceutical target. Recently, mutations in PPM1D were observed in patients that developed secondary cancer after receiving a chemotherapy. This review will discuss the role of PPM1D in development of the secondary cancers as well as potential use of small-molecule inhibitors as prevention to causing these adverse effects of chemotherapy.
Permanent Link: http://hdl.handle.net/11104/0295007