What question did this study set out to answer?

The research aims to understand how to overcome adaptive resistance to KRASG12D blockade in pancreatic cancer.

March 12, 2026Open Access

Overcoming adaptive resistance to KRASG12D blockade in pancreatic cancer through vertical pathway inhibition

Key Points

The research aims to understand how to overcome adaptive resistance to KRASG12D blockade in pancreatic cancer.
Targeted the RAS-MAPK pathway
Utilized combinations of mutant-selective KRAS inhibitors
Incorporated RAS(ON) multi-selective inhibitors
Analyzed cell state interactions
Identified RAS-MAPK reactivation as a mechanism of resistance.
Demonstrated effectiveness of combining KRAS inhibitors with multi-selective inhibitors.
Suggests a universal strategy to overcome resistance in PDAC treatment.

Abstract

In PDAC, adaptive RAS-MAPK reactivation following KRASG12D inhibition can be mediated by different RTKs and influenced by cell state. Combinations of mutant-selective KRASi and RAS(ON) multi-selective inhibitors may represent a promising universal strategy to surmount adaptive resistance in PDAC patients.

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Authors

Qingxiang Lin

Alvin A. Morales-Giron

Conrad Sander

Journals

Clinical Cancer Research

Actions

Institutions

Massachusetts General Hospital

Center for Cancer Research

Roswell Park Comprehensive Cancer Center

References and Citations

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Building similarity graph...

Analyzing shared references across papers

Overcoming adaptive resistance to KRASG12D blockade in pancreatic cancer through vertical pathway inhibition

Key Points

Abstract

Citation Network

Connected Papers

Discussion

Authors

Journals

Actions

Institutions

References and Citations

Citation Network

Connected Papers

Discussion

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