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CONQUERING KRAS IN PANCREATIC CANCER

Pancreatic ductal adenocarcinoma (PDAC) is the most common form of pancreatic cancer and the third leading cause of cancer deaths in the US. Most patients diagnosed with PDAC die from their disease within one year of diagnosis. With a five-year survival rate of approximately 16%, pancreatic cancer is an aggressive and often treatment-resistant disease with few effective treatment options.

Pancreatic ductal adenocarcinoma (PDAC) is the most common form of pancreatic cancer and the third leading cause of cancer deaths in the US. Most patients diagnosed with PDAC die from their disease within one year of diagnosis. With a five-year survival rate of approximately 16%, pancreatic cancer is an aggressive and often treatment-resistant disease with few effective treatment options.

PROJECT HIGHLIGHTS

The Conquering KRAS in Pancreatic Cancer project was supported in partnership with the Lustgarten Foundation. Lustgarten is the largest private funder of pancreatic cancer researchers. Lustgarten has a singular mission: transforming pancreatic cancer into a curable disease. Read More

    • The KRAS gene, which is altered in more than 90% of pancreas cancers, has long been believed to be undruggable.
    • With promising KRAS-targeting therapies now advancing through clinical development, the field has entered a new era of treatment for patients with pancreatic cancer.
    • The Conquering KRAS in Pancreatic Cancer team integrated clinical and laboratory approaches to understand why patients do or do not respond to the RAS-directed therapies, using breakthrough single-cell technologies to deeply investigate biology in organoids, mice, and humans.
    • The TeamLab established a close collaboration with Revolution Medicines to accelerate RAS inhibitor research in pancreatic cancer. By bringing together patients and expertise across Break Through Cancer clinical sites, the TeamLab successfully collected tumor and blood samples throughout patients’ treatment journeys, generating what may become one of the most deeply profiled clinical studies ever conducted in pancreatic cancer.
    • The Conquering KRAS in Pancreatic Cancer project continues to be supported in partnership with the Lustgarten Foundation

TeamLab Publications

TeamLab investigators have published foundational research advancing our understanding of KRAS biology, pancreatic cancer, and mechanisms of response and resistance to KRAS-directed therapies.

A First-of-its-kind Clinical Trial with Revolution Medicines

The TeamLab launched a unique Phase 1 trial for pancreatic cancer combined Revolution Medicines’ daraxonrasib with advanced technologies and serial biopsies to uncover critical insights into pancreatic cancer response and resistance. Dr. Andrew Aguirre of Dana-Farber Cancer Institute and one of the lead investigators on the trial explains it’s potential to transform our understanding of the disease.

MEET THE TEAM

AllDana-Farber Cancer InstituteMemorial Sloan Kettering Cancer CenterMIT’s Koch Institute for Integrative Cancer ResearchThe Sidney Kimmel Comprehensive Cancer Center at Johns HopkinsThe University of Texas MD Anderson Cancer Center

MEET THE TEAM

View Team
AllDana-Farber Cancer InstituteMemorial Sloan Kettering Cancer CenterMIT’s Koch Institute for Integrative Cancer ResearchThe Sidney Kimmel Comprehensive Cancer Center at Johns HopkinsThe University of Texas MD Anderson Cancer Center

PROJECT SUMMARY

Like all cancers, pancreatic ductal adenocarcinoma (PDAC) is caused by mutations in genes that collectively drive cells to divide and grow in the absence of the normal controls. In the case of PDAC, the key driver of disease development are mutations in a gene called KRAS. KRAS-function is analogous to a binary switch, with cancer-associated mutations preventing the switch from going to the OFF position, resulting in continues KRAS activity driving uncontrolled tumor growth.

Because KRAS lacks easily targetable ‘pockets’ and has a high affinity for its natural substrate KRAS and related pathways were long considered one of the greatest challenges in cancer research. Recently however, major advances have led to the development of both mutant-selective KRAS inhibitors and broader RAS-directed therapies that have demonstrated encouraging activity in clinical trials. These breakthroughs have transformed the outlook for pancreatic cancer research, and the field is now on the cusp of a revolution in the treatment of PDAC patients.

The primary goal of the Conquering KRAS in Pancreatic Cancer project was to understand tumor-adaptation and development of resistance to effective KRAS-directed therapies for pancreatic cancer by combining rigorous preclinical research with innovative clinical studies. Through pharmaceutical partnerships, including a close collaboration with Revolution Medicines, and extensive research and clinical infrastructure, the TeamLab established one of the field’s most comprehensive efforts to understand how patients respond and adapt to RAS-directed treatment.

The Conquering KRAS in Pancreatic Cancer TeamLab brought together key thought leaders with expertise in KRAS function, PDAC biology and pathology, computational biology, single-cell analyses, patient-derived and animal models, along with and clinical trials. Together, the team rapidly initiated preclinical and clinical studies, developed a deeply profiled clinical cohort, and established a highly collaborative research program capable of generating unprecedented insights into response and resistance to RAS-directed therapy.

Through these collective studies, the TeamLab helped advance a new era of RAS-directed therapy in pancreatic cancer while creating a foundation for future investigations into combination treatment strategies. The clinical, scientific, and translational infrastructure established through this effort now serves as the basis for the next phase of research focused on developing more durable treatment responses for patients with pancreatic cancer, ultimately improving the duration and quality of life for those diagnosed with this difficult disease.

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