The Latest Research: The 2026 AACR Conference on Pancreatic Cancer

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Pancreatic cancer research took center stage in San Diego, California, at the end of September in 2026.

More than 600 attendees from academia, medicine, industry, and patient advocacy came together to discuss the latest developments at the annual AACR Conference on Pancreatic Cancer: New Frontiers in Biology and Therapeutic Development. The conference covered a number of topics including the rapid advances in precision oncology, KRAS-targeted therapeutics, computational and AI-driven approaches, immunotherapy, and translational clinical research. As always, Let’s Win is providing you a glimpse of some of this important work. We will cover some of these areas in more depth in the coming months, so stay tuned.

Dissecting How Resistance to KRAS Inhibitors Develops

KRAS inhibitors, including the recently approved Rasonque (daraxonrasib), played prominent roles in several presentations. One focus of research is how resistance to Rasonque develops, on average about seven months after treatment begins. Andrew Aguirre, M.D., Ph.D., a pancreatic cancer specialist at Dana-Farber Cancer Institute (Boston, Massachusetts), and colleagues want to find out why. In an early study supported by the Lustgarten Foundation, Break Through Cancer, and Rasonque developer Revolution Medicines, 66 patients with advanced pancreatic cancer underwent biopsies. The first biopsy was performed before daraxonrasib treatment began; participants had two more biopsies, the last occurring after the drug stopped working. By about two weeks after treatment initiation a patient’s cancer cells diminished by about half, and the remaining cancer cells looked less abnormal. That finding hinted that daraxonrasib may work better when combined with chemotherapy.

In another study that looked at blood samples of 44 patients, researchers found an overproduction (increase in the number of copies) of the mutant KRAS gene targeted by daraxonrasib. This allowed cancer cells to flood the system with excess RAS protein and outcompete the inhibitor. Researchers are now seeing the same overproduction happening in the biopsy study participants. That study has received more funding, to see how tumors respond to daraxonrasib in combination with other treatment.

Daraxonrasib Combos

SELLAS Life Sciences Group presented preclinical data from studies evaluating SLS009 (tambiciclib), a CDK9 inhibitor, in patient-derived organoid models of pancreatic cancer. The studies, conducted in collaboration with researchers at the University of Wisconsin–Madison, evaluated SLS009 in MYC-amplified pancreatic ductal adenocarcinoma models, including a model resistant to daraxonrasib, as well as in combination with the BET inhibitor ZEN3694.

In the preclinical studies SLS009 demonstrated substantially greater single-agent activity than daraxonrasib in the daraxonrasib-resistant model. The combination of SLS009 and daraxonrasib significantly increased cancer cell death. SLS009 combined with ZEN-3694 demonstrated synergistic activity, producing greater apoptosis and necrosis than either agent alone. The SLS009/ZEN-3694 combination produced sustained suppression of MYC RNA and reduced expression of MYC and MCL-1 proteins, consistent with disruption of transcriptional pathways supporting tumor cell survival.

Potential Treatment Plus Cachexia Breakthrough

Immuneering presented new data in a poster titled “Atebimetinib Reduces Tumor Volume and Preserves Body Mass: A Dual Mechanism for Extended Survival in Pancreatic Cancer.” The study evaluated the relationship between body mass preservation, tumor volume reduction, and overall survival in metastatic pancreatic cancer patients who were treated with atebimetinib in combination with modified gemcitabine/nab-paclitaxel (mGnP) as a first treatment (first-line) for the disease. Atebimetinib + mGnP is currently being evaluated in a the phase III MAPKeeper 301 clinical trial as a first-line treatment for patients with metastatic pancreatic cancer.

Median overall survival of 17.3 months was previously reported in 55 participants who received this treatment; 84 percent of evaluable patients had stable or increased weight at three months. In the new analysis the proportion of patients demonstrating stable or increasing weight was approximately two-fold higher among atebimetinib + mGnP-treated patients.

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Among the patients treated with atebimetinib + mGnP, those with stable or increased weight at three months had significantly longer overall survival than patients who experienced weight loss at three months. Median overall survival had not been reached in the weight-stable or weight-gain group after median follow-up of 15.2 months.

Overall survival among patients with deeper tumor volume reductions, defined as a sum of longest diameters (SLD) reduction of at least 30 percent, was comparable to overall survival among patients with moderate tumor volume reductions of between 0 and 30 percent. Median overall survival was not reached in either group. In contrast, median overall survival was reached among patients without a measured reduction in SLD. The findings suggest that achieving tumor volume reduction may be more important to overall survival than the depth of tumor reduction and that clinically meaningful benefit may extend to patients whose tumor shrinkage does not meet the threshold for a RECIST partial response.

Honoring A Legend

Kevan Shokat, Ph.D., was named the 2026 Stephenson Global Laureate at the conference. Shokat was only 18 years old when researchers discovered the first family of cancer-causing genes, which included the notorious KRAS, and he was a graduate student when scientists first learned how KRAS works. He was a postdoctoral fellow when the protein was deemed undruggable. Shokat, a professor in the department of Cellular and Molecular Pharmacology at the University of California San Francisco, a professor in the Department of Chemistry at the University of California Berkeley, and a Howard Hughes Medical Institute investigator, wasn’t buying it and was determined to find a way to make the undruggable druggable.

Shokat, a co-founder of Revolution Medicines, traced the history of discoveries that culminated in the design of the first generation of mutant-KRAS inhibitors in his lab, which eventually led to approved drugs and a portfolio of more than 90 different candidates currently in clinical development. He also illustrated the factors that made KRAS such a challenging drug target and how chemistry helped solve the puzzle.