2026-06-14T00:34:14Zhttps://repisalud.isciii.es/rest/oai/requestoai:repisalud.isciii.es:20.500.12105/147022024-11-29T14:51:18Zcom_20.500.12105_2173com_20.500.12105_2051col_20.500.12105_19597
Repisalud
author
Drosten, Matthias
author
Barbacid, Mariano
funder
Unión Europea. Comisión Europea. European Research Council (ERC)
funder
Government of Spain
funder
Unión Europea. Comisión Europea
funder
Comunidad de Madrid (España)
funder
CRIS contra el Cáncer
funder
Fundación AXA
2022-07-13T09:12:47Z
2022-07-13T09:12:47Z
2022-05-16
Mol Oncol. 2022;16(5):1057-1071.
10.1002/1878-0261.13168
1878-0261
Molecular oncology
34951114
http://hdl.handle.net/20.500.12105/14702
For decades, KRAS mutant lung adenocarcinomas (LUAD) have been refractory to therapeutic strategies based on personalized medicine owing to the complexity of designing inhibitors to selectively target KRAS and downstream targets with acceptable toxicities. The recent development of selective KRASG12C inhibitors represents a landmark after 40 years of intense research efforts since the identification of KRAS as a human oncogene. Here, we discuss the mechanisms responsible for the rapid development of resistance to these inhibitors, as well as potential strategies to overcome this limitation. Other therapeutic strategies aimed at inhibiting KRAS oncogenic signaling by targeting either upstream activators or downstream effectors are also reviewed. Finally, we discuss the effect of targeting the mitogen-activated protein kinase (MAPK) pathway, both based on the failure of MEK and ERK inhibitors in clinical trials, as well as on the recent identification of RAF1 as a potential target due to its MAPK-independent activity. These new developments, taken together, are likely to open new avenues to effectively treat KRAS mutant LUAD.
eng
genetically engineered mouse tumor models
KRAS(G12C) inhibitors
lung adenocarcinoma
RAF1
RAS signaling
tumor resistance
Targeting KRAS mutant lung cancer: light at the end of the tunnel.
journal article
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URL
https://repisalud.isciii.es/bitstreams/95fbfcdf-ebfc-4ba0-a02e-bb4b9a94d63b/download
File
MD5
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application/pdf
TargetingKRASmutantlung_2021.pdf
URL
https://repisalud.isciii.es/bitstreams/27669a04-0bab-4503-836c-140bf4a0c445/download
File
MD5
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text/plain
TargetingKRASmutantlung_2021.pdf.txt