Combined treatment with the AXL inhibitor bemcentinib together with the RAS(ON) multi-selective tri-complex inhibitor RMC-7977 (RASi) or the ERK-selective inhibitor SCH772984 (ERKi) significantly enhanced growth suppression in human KRAS-mutant pancreatic and lung cancer models.
By integrating adaptive response to KRAS inhibition with anti-tumor immunity, AXL represents a mechanistically actionable vulnerability whose inhibition deepens and prolongs responses to both allele-specific and pan-KRAS-targeted therapies.
F. Thege, A. Kramer, Norbert Kreisz et al.· bioRxiv· 0 citations
It is demonstrated that compensatory AKT activation limits the efficacy of cabozantinib in ALL and the combination of cabozantinib and capivasertib as a promising therapeutic strategy for refractory ALL is established.
Hai-Hong Gao, Yi Zhan, Miao-Ying Bao et al.· Molecular Cancer Therapeutic...· 0 citations
XPO1 inhibitor Eltanexor enhances the efficacy and durability of KRAS and pan-RAS inhibition in PDAC models and provides a preclinical rationale for clinically evaluating Eltanexor in combination with RAS-targeted therapies to delay or overcome adaptive resistance in KRAS-mutant PDAC.
H. Y. Khan, M. Al-Hallak, A. Aboukameel et al.· Cancer Letters· 0 citations
Pancreatic ductal adenocarcinoma (PDAC) remains one of the most lethal malignancies. Surgery is the only potentially curative treatment, yet approximately 85% of patients present with unresectable disease. For these patients, chemotherapy remains the standard treatment, though nearly all develop resistance and diseas...
K. Gulay, A. Martsinkovskiy, A. Lowy et al.· Cancer Research· 0 citations
These findings identify distinct adaptive pathways orchestrating RAS-dependent versus RAS-independent resistance in PDAC and propose combination strategies for clinical evaluation to enhance KRAS-directed therapy durability.
Hsiu-Chi Ting, Sun Kim, V. Gaeth et al.· Cancer Research· 0 citations
Despite the success of chimeric antigen receptor (CAR) T cell therapy for liquid cancers, it has provided minimal clinical benefit in solid cancers, including pancreatic ductal adenocarcinoma (PDAC). We have previously shown that pharmacological RAS inhibition favorably remodels the PDAC tumor immune microenviron...
Jayne C. McDevitt, Fei-Yan Mo, Connor J. Hennessey et al.· Cancer Research· 0 citations
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