How KRAS drives pancreatic cancer is explained, the main direct and indirect treatment approaches are summarized, and a major challenge is highlighted: tumors often develop resistance when KRAS inhibitors are used alone.
Abstract
Simple Summary Pancreatic cancer remains one of the most difficult cancers to treat, and most tumors carry changes in a gene called KRAS. For many years, KRAS was considered impossible to target with drugs. Recent advances have led to the development of medicines that directly block specific KRAS mutations, as well as broader treatments that can inhibit several KRAS forms. This review explains how KRAS drives pancreatic cancer, summarizes the main direct and indirect treatment approaches, and discusses ongoing clinical trials. It also highlights a major challenge: tumors often develop resistance when KRAS inhibitors are used alone. Combining these drugs with chemotherapy, immunotherapy, or treatments aimed at other cancer pathways may produce stronger and longer-lasting responses. Although most approaches are still being tested, KRAS-directed therapy represents an important step toward more precise and effective treatment for patients with pancreatic cancer.
Pancreatic adenocarcinoma (PDAC) is a RAS-driven cancer with poor prognosis. Although tremendous progress has been made in other cancers with the development of targeted therapies and immunotherapy, cytotoxic chemotherapy remains the mainstay of treatment for PDAC. For decades, the therapeutic development of RAS-target...
L. Chan, T.-T.-A. Kwong, Johnny C. W. Yau et al.· ESMO gastrointestinal oncolo...· 0 citations
INTRODUCTION
Pancreatic ductal adenocarcinoma (PDAC) is an aggressive malignancy in which activating KRAS mutations, present in more than 90% of tumors, constitute the principal oncogenic driver. Advances in structural biology have enabled the pharmacologic targeting of KRAS, a protein historically regarded as 'undrugg...
Joanna Kreidi, C. Hoyek, C. Eslinger et al.· Expert Opinion on Biological...· 0 citations
These breakthroughs have validated direct KRAS inhibition as an effective therapeutic strategy, however, durable clinical responses remain limited by intrinsic and acquired resistance, pathway reactivation, tumour heterogeneity, and the lack of effective therapies for non-G12C KRAS mutations.
Pasham Uma, Dandotikar Neha, R. Manisha et al.· International Journal of Inn...· 0 citations
The rapid evolution of KRAS-targeted therapeutic agents represents a shift from allele-specific inhibition towards a strategy that is mutation/context-dependent, thereby creating further clinical translation opportunities and increased patient benefit.
Srijita Chatterjee, S. Arya, Nidhi Sharma et al.· Medical Oncology· 0 citations
Simple Summary Pancreatic cancer usually responds poorly to drugs that release the brakes on immune cells. Combining these drugs with other treatments may help, but early responses do not show which treatment contributed or whether patients live longer. This review examines clinical studies alongside four interacting p...
Bode T. Eisenmenger, Abraham S. Rappaport, Liam H. Connell et al.· Cancers· 0 citations
This review synthesizes current knowledge on KRAS resistance mechanisms and highlights emerging therapeutic strategies, including rational combination approaches, enhanced RAS pathway suppression, targeted protein degradation, and KRAS-directed immunotherapies.
Rawan Salih, F. Sirajudeen, Mohamed Rahmani· Journal of Advanced Research· 0 citations
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