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KRAS Inhibition in Pancreatic Ductal Adenocarcinoma
Roshini Pradeep1, Nooredeen Jamal Isbeih1, Freya F Abraham2
1Department of Hematology and Oncology, University of Arizona College of Medicine-Phoenix, Banner MD Anderson Cancer Center, Gilbert, AZ 85234, USA.
Journal of Clinical Medicine
|January 28, 2026
Summary
This review details the evolving understanding of KRAS mutations in pancreatic ductal adenocarcinoma (PDAC). It covers historical context, therapeutic strategies like covalent inhibitors and targeted protein degradation, and future clinical trials for PDAC treatment.
Area of Science:
- Oncology
- Molecular Biology
- Genetics
Background:
- KRAS alterations are prevalent in over 90% of pancreatic ductal adenocarcinoma (PDAC) cases.
- RAS proteins play a central role in PDAC biology and oncogenesis.
- Understanding KRAS pathways is crucial for developing effective PDAC therapies.
Purpose of the Study:
- To review the historical understanding of RAS in PDAC.
- To summarize current and emerging therapeutic strategies targeting KRAS.
- To outline the clinical trial landscape and future research directions for KRAS-targeted therapies in PDAC.
Main Methods:
- Literature review of historical and current research on KRAS in PDAC.
- Analysis of various therapeutic approaches, including covalent inhibitors, targeted protein degradation, and panRAS inhibitors.
- Examination of preclinical and clinical trial data for KRAS-directed therapies.
Main Results:
- KRAS G12C inhibitors represent early successes, with ongoing efforts targeting other KRAS mutations.
- New strategies include targeted protein degradation, panRAS inhibitors, and blockade of signaling crosstalk.
- Synthetic lethality approaches and KRAS-specific immunotherapies are transitioning to clinical trials.
Conclusions:
- Significant progress has been made in targeting KRAS in PDAC, moving beyond KRAS G12C.
- A diverse array of therapeutic strategies are under investigation, addressing resistance and upstream signaling.
- The clinical trial landscape for KRAS-targeted therapies in PDAC is expanding, offering new hope for patients.
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