Nicholas Hornstein, Gastrointestinal Medical Oncologist at Northwell Health, shared a post on X:
“I had the chance to speak at the Northwell Health Pancreas Symposium on Emerging Therapies in PDAC.
Big picture: we are not going to chemotherapy our way out of pancreatic cancer. The next gains come from biology-driven, precision strategies.
Why progress has been slow:
- ~90% of PDAC is KRAS-mutant (mostly G12D/V)
- Dense desmoplastic stroma limits drug delivery
- Immune-excluded TME → PD-1 monotherapy fails
- Early systemic dissemination
Cytotoxics plateaued. Targeting drivers + vulnerabilities is mandatory.
The KRAS revolution is real.
- From undruggable’ to a drug class:
- G12C inhibitors = proof of concept
- Pan-RAS(ON) inhibitors (e.g. RMC-6236) with activity across G12X
- G12D-selective inhibitors, degraders, RNAi approaches
This is now a menu, not a moonshot.
Immunotherapy isn’t dead in PDAC—it was misapplied.
The shift: high-potency vaccines and cellular therapies in low-burden disease.
- Personalized mRNA neoantigen vaccines post-resection
- KRAS-directed peptide vaccines in MRD+ patients
- TCR-T (KRAS G12D, TP53) and CAR-T in selected cases
Context matters.
Take-home for trainees and clinicians:
PDAC care is moving from binary chemo choices to biomarker-driven therapy. KRAS strategies, rare fusions, HRR defects, vaccines, cell therapy—all demand comprehensive DNA + RNA profiling. Molecular testing is no longer optional.”
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