In:
Science Signaling, American Association for the Advancement of Science (AAAS), Vol. 15, No. 754 ( 2022-10-04)
Abstract:
The kinase PLK1 mediates the process of cell division, which drives the growth of many cancers. Using genetically modified mouse models of a common form of human lung adenocarcinoma in which PLK1 abundance is increased, Kong et al. identified an independent mechanism through which PLK1 fueled tumor growth. In Kras -mutant murine lung adenocarcinoma cells in culture and in mice, PLK1 kinase activity resulted in increased expression of the gene encoding the receptor kinase RET. Together with KRAS, RET activated the mitogen-activated protein kinase (MAPK) pathway, which promotes tumor growth. Combining the MAPK pathway inhibitor trametinib with the RET inhibitor pralsetinib (both of which are clinically approved for some lung cancers) induced tumor regression and prolonged survival in a mouse model of lung cancer with high PLK1 abundance. The findings suggest a potential therapeutic strategy for some lung adenocarcinomas.
Type of Medium:
Online Resource
ISSN:
1945-0877
,
1937-9145
DOI:
10.1126/scisignal.abj4009
Language:
English
Publisher:
American Association for the Advancement of Science (AAAS)
Publication Date:
2022
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