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Conquering KRAS in Pancreatic Cancer

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 10%, pancreatic cancer is an aggressive and treatment-refractory 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 10%, pancreatic cancer is an aggressive and treatment-refractory disease with few effective treatment options.

PROJECT HIGHLIGHTS

The Conquering KRAS in Pancreatic Cancer project will be 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 many promising new KRAS-targeting therapies either now available or on the horizon, the field may be on the cusp of a revolution in treatment for patients with pancreatic cancer.
    • The Conquering KRAS in Pancreatic Cancer team will integrate clinical and laboratory approaches to understand why patients do or do not respond to the new therapies using breakthrough single-cell technologies to deeply investigate biology in organoids, mice, and humans.
    • The team will develop pharmaceutical partnerships to accelerate the translation of new KRAS inhibitors into effective drugs for this disease. The large number of patients at Break Through Cancer partner institutions will enable trials that would be difficult at a single institution since some patients have rare but important KRAS mutations.
    • The Conquering KRAS in Pancreatic Cancer project will be supported in partnership with the Lustgarten Foundation.

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 is a gene called KRAS. KRAS is analogous to a binary switch, with cancer-associated mutations preventing the switch from going to the OFF position, resulting in dysregulated growth.

Because many cells in the body need the normal KRAS switch to function, drugs that would indiscriminately switch KRAS off would be expected to be highly toxic. Recently however, the prospects for effectively targeting KRAS in PDAC and other diseases have improved with the development of drugs that act only on the mutant form of KRAS, and these have shown encouraging activity in clinical trials, with one drug in this class approved for the treatment of lung cancer. With many promising new KRAS-targeting therapies on the horizon, the field may be on the cusp of a revolution in the treatment of PDAC patients. There is an urgent need to act quickly and collaboratively to understand how to best implement KRAS inhibition to maximally benefit PDAC patients.

There are a number of challenges confronting this effort. First, as with most forms of “targeted therapies” in cancer, tumor cells eventually become resistant to KRAS inhibition alone. The key to success will therefore be to understand how resistance comes about, and how to use these new drugs in combination with other agents, analogous to combination therapies for other cancers and for HIV. Another challenge is that there are several distinct cancer-causing mutations in KRAS, so drug combinations may need to be tailored to each specific KRAS variant. This will require that clinical trials draw from a large pool of patients whose specific KRAS mutation status has been established.

The primary goal of the Conquering KRAS in Pancreatic Cancer project is to develop effective combination therapy strategies to target oncogenic KRAS in PDAC through rigorous preclinical studies and human clinical trials, backed by the extensive research and clinical infrastructure of five major cancer centers committed to advancing the care of PDAC patients.

The Conquering KRAS in Pancreatic Cancer team will bring together key thought leaders with expertise in KRAS function, PDAC biology, computational biology, single-cell analyses, patient-derived, and animal modeling and clinical trials to rapidly initiate rigorous preclinical and clinical studies, cooperatively evaluate data, and prioritize optimal therapeutic strategies.

The team will develop pharmaceutical partnerships to accelerate the translation of new KRAS inhibitors into effective drugs. Clinical trials with these new drugs will have the advantage of access to a large number of patients at the Break Through Cancer partner institutions.

Through these collective studies, this project aims to leverage new KRAS inhibitors to change the face of treatment for pancreatic cancer patients, ultimately improving the duration and quality of life for those diagnosed with this difficult disease.

MAKE A DIFFERENCE

Break Through Cancer was created in February 2021 with an extraordinary matching gift of $250,000,000. Every gift to the Foundation supports groundbreaking cancer research and helps us to meet our matching commitment.

For questions about giving please email Lisa Schwarz, Chief Philanthropy Officer at LMS@BreakThroughCancer.org

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