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Jefferson Surgical Solutions

Scientific discoveries and advances often come in an unpredictable cadence. Over the course of my 40 years as a surgeon treating patients with pancreatic and related cancers, we have seen overall five-year patient survival rates improve more than six-fold from under 2% to over 13%. This improvement has its genesis in many areas – improved patient selection and surgical results, better imaging, advances in nursing and critical care and new oncologic treatment options. One area that has eluded progress for decades has been targeting the RAS oncogene mutations common in nearly all pancreatic cancers.

Therapeutic targeting of RAS with a drug had been thought impossible. But in the last few years, the development of covalent KRAS G12C inhibitors, which lock the mutant protein in an “off” state, has shown that targeting RAS is feasible (although only 2% of patients harbor a G12C KRAS mutation). Now, a recently discovered orally bioavailable RAS multi-selective, non-covalent inhibitor with activity against all RAS mutants has been studied – daraxonrasib.

While it is unlikely that this particular drug will ultimately be the sought-after panacea for patients with pancreatic cancer, the early results indicate reasonable anti-tumor activity with manageable side effects. There are certain to be other pan-RAS inhibitors that will improve patient outcomes (not only in patients with pancreatic cancers, but in other RAS-driven tumors such as lung, colorectal, appendiceal, small bowel and endometrial cancers).

Progress in science may be unpredictable, and the cadence of progress may vary widely, but it is heartening to see advances in the field of oncology yield meaningful results for patients. Science is, after all, the systematic process of gathering knowledge about the physical world through observation, testable hypotheses and experimentation.

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