Targeting SHP2 - Stand Up To Cancer

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Pancreatic Cancer Collective Research Team:
Targeting SHP2 in Pancreatic Cancer New Therapies Challenge

Grant Terms
Round 1: November 2018–December 2019
Round 2: January 2020–June 2023

The team is studying whether inhibiting cellular processes in pancreatic tumors can stop the out-of-control growth that is characteristic of cancer. Pancreatic cancers with mutations in the KRAS gene are weakened when a protein called SHP2 is blocked in the RAS pathway—a cellular pathway that may be essential to the growth of pancreatic cancer cells. Another means to block this pathway involves a protein called MEK. In Round 1 pre-clinical work, the team has shown that inhibiting both of these components, they can better control growth of pancreatic cancertumors. In Round 2, the team will test the combination in a phase 1/1b clinical trial to better understand how this double inhibition works and to inform continued clinical trials.

Supported by:


More than 90% of pancreatic tumors carry a mutation in the KRAS oncogene. The RAS pathway may be essential to promote the growth of pancreatic cancerous cells. This pathway helps transmit proliferation-promoting signals from the cell’s surface receptors toward the nucleus, where these signals affect the regulation of other key genes that instruct the cell to divide. Mutant RAS genes become more active in signaling, and therefore keep pushing the cell toward uncontrolled proliferation. So far, no targeted therapies are clinically available against the active protein encoded by the mutant RAS gene.

The team has discovered that tumors carrying an activating KRAS mutation are sensitive to the inhibition of SHP2, a protein that helps the transmission of the growth-promoting signal from the cell surface receptors. Moreover, the team has found that SHP2 inhibitors cooperate with inhibitors of MEK, a key RAS downstream effector, to achieve better control of tumor growth. Given these findings, the researchers are studying a combination of SHP2 inhibitors and MEK inhibitors for the treatment of KRAS-mutant pancreatic cancer patients.

This team is part of the Pancreatic Cancer Collective, an initiative of the Lustgarten Foundation for Pancreatic Cancer Research and Stand Up To Cancer.


The top scientists and researchers on the Pancreatic Cancer Collective Research Team: Targeting SHP2 in Pancreatic Cancer New Therapies Challenge come from a variety of backgrounds and disciplines, which leads them to great insights upon collaboration. Learn more about the Pancreatic Cancer Collective Research Team: Targeting SHP2 in Pancreatic Cancer New Therapies Challenge.

Research Team Members

Rene Bernards, PhD
Netherlands Cancer Institute

Emile Voest, MD, PhD
Netherlands Cancer Institute

Hana Algül, MD, MPH
Technical University of Munich

Henri van Luenen, PhD
Netherlands Cancer Institute
Project Manager

Ab Doorn

Otto Lutz

“By joining efforts between two different countries, hospitals, and research centers, and with the support of the Pancreatic Cancer Collective, we aim at bringing the rational SHP2 + MEK inhibitors combination therapy to the clinic, for the benefit of pancreatic cancer patients.”

Rene Bernards, PhD
Netherlands Cancer Institute


Stand Up To Cancer’s research projects are designed to foster collaborative, swift translational research. The hallmarks of these efforts include rigorous application and selection procedures, sufficient funding to allow scientists to focus on the objectives of the grant, and reviews by senior scientists every six months. These reviews help the investigators capitalize on the latest findings, address potential roadblocks, and collaboratively evolve as the science requires. Please click on the link to see summaries of the research results so far for the Pancreatic Cancer Collective Research Team: Targeting SHP2 in Pancreatic Cancer New Therapies Challenge.



This team started its work in November 2018; links to publications will be posted when they are available.


Cancer clinical trials allow researchers to study innovative and potentially life-saving new treatments. The goal is to find treatments that are better than what’s currently available, in fact the therapies offered to today’s cancer patients were almost all studied and made possible by people participating in clinical trials. But many cancer clinical trials don’t get completed because not enough people participate.

At, you’ll find information and answers to common questions about clinical trials. Learn more and talk to your doctor to see if a clinical trial may be the best choice for you.



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