Real-time sequencing and organoid-based screens in pancreatic cancer could place new targets and biomarkers in the hands of drug developers looking for ways to side-step KRAS, a gene mutated in 90% of patients.
Because KRAS mutations are so abundant in pancreatic cancer, companies and physicians have been slow to even test tumors for other targets. Two papers show the new techniques have already uncovered enough actionable data from patient samples to argue tumor profiling should be a mainstay of research and clinical care, regardless of KRAS status.
At least three biotechs are developing technologies for drugging KRAS, a GTPase that has been notoriously intractable to drug development (see “P53 and RAS: Back from the Dead”).
But the prevalence of KRAS mutations has created a chicken and egg problem for the field -- without a variety of actionable mutations clinicians see little reason to profile their patients’ tumors. Not profiling them precludes finding new targets or biomarkers that could better tailor chemotherapy regimens.
The new studies, both published in Cancer Discovery, could help break that cycle, making the case for collecting patient samples at the time of diagnosis and characterizing them to guide treatment.
In one paper, researchers from the Dana-Farber Cancer Institute collected biopsies from 79 pancreatic cancer patients under a standardized trial protocol, dubbed PancSeq, to identify actionable targets via DNA and RNA profiling.
“We hypothesized that we would see things, either in patients who had a KRAS mutation or in the 10% that don’t, that could potentially be targetable. And we felt that we