Pancreatic malignancies remain some of the most challenging cancers to treat. Experts anticipate over 52,000 pancreatic cancer-related deaths this year. Sadly, the five-year survival rate for pancreatic cancer remains under 15%. As many patients don’t experience symptoms, the diagnosis of pancreatic cancer often occurs at advanced stages, with minimal treatment options. This presents a desperate need for novel and efficacious therapies to treat pancreatic cancer, particularly late-stage disease.
An exciting study, recently published in the Proceedings of the National Academy of Sciences of the United States of America (PNAS), provides breakthrough data that may help increase treatment efficacy and prolong survival for pancreatic cancer patients.
The pre-clinical study, performed in mouse models of pancreatic ductal adenocarcinoma (PDAC), one of the most common, and also one of the most aggressive, types of pancreatic cancer.
Researchers used a combination approach to treat PDAC-bearing mice, administering drugs targeting three pathways known to facilitate pancreatic tumor growth and survival. The triple-target strategy targeted the KRAS, EGFR, and STAT3 pathways with RMC-6236/daraxonrasib, afatinib, and SD36, respectively.
RAS inhibitors, such as daraxonrasib, have gained traction in oncology research in recent years as they demonstrated benefits for the treatment of pancreatic cancer. However, their effects often remain short-lived as many tumors develop resistance to the drug.
When researchers combined daraxonrasib with atatinib and SD36, they saw complete regression of pre-clinical PDAC tumors. Notably, 200 days after treatment, the mice whose tumors regressed showed no sign of tumor recurrence.
The study's comprehensive nature adds to the interest in its promising results. Although fully preclinical, the study used different mouse models and achieved similar results. The study first used orthotopic PDAC tumors, meaning they occur in the same anatomical location in the mouse pancreas as in humans, making the results highly translatable. In addition, the researchers used genetically engineered mouse tumors and patient-derived tumor xenografts, models where small pieces of a patient’s tumor are processed and implanted into mice. The robust nature of the study and the strength of the findings provide a strong rationale for future work in the clinical setting.
Sources: CA Cancer J Clin, PNAS, World J Gastrointest Oncol, J Med Chem, Nature