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Title:

Extensive preclinical validation of combined RMC-4550 and LY3214996 supports clinical investigation for KRAS mutant pancreatic cancer.

Document type:
Journal Article; Research Support, Non-U.S. Gov't
Author(s):
Frank, Katrin J; Mulero-Sánchez, Antonio; Berninger, Alexandra; Ruiz-Cañas, Laura; Bosma, Astrid; Görgülü, Kıvanç; Wu, Nan; Diakopoulos, Kalliope N; Kaya-Aksoy, Ezgi; Ruess, Dietrich A; Kabacaoğlu, Derya; Schmidt, Fränze; Kohlmann, Larissa; van Tellingen, Olaf; Thijssen, Bram; van de Ven, Marieke; Proost, Natalie; Kossatz, Susanne; Weber, Wolfgang A; Sainz, Bruno; Bernards, Rene; Algül, Hana; Lesina, Marina; Mainardi, Sara
Abstract:
Over 90% of pancreatic cancers present mutations in KRAS, one of the most common oncogenic drivers overall. Currently, most KRAS mutant isoforms cannot be targeted directly. Moreover, targeting single RAS downstream effectors induces adaptive resistance mechanisms. We report here on the combined inhibition of SHP2, upstream of KRAS, using the allosteric inhibitor RMC-4550 and of ERK, downstream of KRAS, using LY3214996. This combination shows synergistic anti-cancer activity in vitro, superior d...     »
Journal title abbreviation:
Cell Rep Med
Year:
2022
Journal volume:
3
Journal issue:
11
Fulltext / DOI:
doi:10.1016/j.xcrm.2022.100815
Pubmed ID:
http://view.ncbi.nlm.nih.gov/pubmed/36384095
TUM Institution:
Klinik und Poliklinik für Nuklearmedizin; Lehrstuhl für Tumormetabolismus (Prof. Algül)
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