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2023 GIST EDUCATION CONFERENCE AND LUNCHEON

The OHSU Knight Cancer Institute and the GIST Cancer Research Fund cordially invite you to Oregon Health & Science University for a one-day education conference highlighting advancements in Gastrointestinal Stromal Tumors (GIST) Research.

Ronald P. DeMatteo MD

Background: GIST is the most common human sarcoma, and approximately 85% of these tumors are attributable to a mutation in either KIT or PDGFRA genes. Imatinib mesylate is a tyrosine kinase inhibitor (TKI) that targets both of these genes and is effective in nearly 80% of patients with GIST. The advent of tyrosine kinase inhibitors has increased the median survival from 1 year to over 5 years. Despite this success, imatinib and the other tyrosine kinase inhibitors are not curative even in patients who respond, and many GISTs develop resistance to these drugs, necessitating further therapeutic approaches. Our lab has recently focused on discovering alternative approaches that may increase the efficacy of these tyrosine kinase inhibitors with combination therapy.

Current Focus & Future Directions: We have been using our immunocompetent, genetically engineered Kit ^V558Δ/+ mouse model which develops a cecal GIST with similar histology, Kit signaling, response to tyrosine kinase inhibitors, and immune response as seen in human GIST. We recently published work on Kit ligand, the natural ligand for the Kit receptor and showed that tumor cells as well as endothelia and smooth muscle cells produce Kit ligand in our mouse model, even after imatinib therapy.

Kit ligand remains an important therapeutic target. In addition, we also recently published details of an in vivo model that was developed to study a particular PDGFRA mutation and the mechanism of tumor persistence following treatment with avapritinib, a drug used after patients develop resistance to imatinib. We found that resistance to avapritinib can be caused by upregulation of myosin light-chain kinase (MYLK) inhibition and suggest that concomitant MYLK inhibition may enable the use of a lower dose of avapritinib to avoid cognitive side effects.

In addition to the above mechanisms, we are also studying various immune targets to block or activate in conjunction with imatinib to enhance imatinib’s anti-tumoral effect. These targets include ICOS, CD40, and VISTA. We are also utilizing recently acquired scRNAseq data of human GIST samples in order to categorize different immune cell populations and their gene expression to correlate to treatment response.

Summary: Our lab continues to search for new therapies to enhance the activity of tyrosine kinase inhibition in the treatment of GIST. We will be working to better understand TAMs in order to recruit and activate these immune cells to enhance the immune response to GIST. We will then be using combination therapy focusing on CD40 with the goal of activating the immune system to work in tandem with imatinib. We are so grateful for your continued support as we work toward these goals of combating human GIST.

DeMatteo Laboratory Personnel:
Ronald P. DeMatteo MD is John Rhea Barton Professor and Chair of Surgery at the University of Pennsylvania. His laboratory has been funded by the NIH since 2001. His laboratory attracts trainees from throughout the country. He will supervise all aspects of the proposal. All of the work in the lab is now focused on GIST.

Ferdi Rossi PhD is a molecular biologist. He has worked with Peter Besmer for over 10 years and now works in our lab. He has multiple projects in GIST.

Shan Zeng PhD is a molecular biologist and is primarily studying the role of gamma delta T cells in GIST.

Drew Tieniber MD is a postdoctoral fellow from the University of Pennsylvania and is using bioinformatics to study the CD8 T cell response to GIST.

Hyunjee Kwak MD is a postdoctoral fellow from the University of California San Francisco – East Bay, and is studying VISTA blockade and CD40 agonism in enhancing imatinib’s anti-tumoral effect.

Katherine Tardy MD is a postdoctoral fellow from Lankenau Medical Center and is studying ICOS blockade to enhance imatinib’s anti-tumoral effect.

Alina Mangold MD is a postdoctoral fellow from Germany and is studying the role of regulatory T cells in the GIST tumor microenviroment and immune response.

Juan Esteban Perez MD is a postdoctoral fellow from the University of Pennsylvania and is working to classify the subtypes of Tumor Associated Macrophages (TAMs) and their role in GIST.

Kevin Do is a research technician currently investigating alternative tyrosine kinase inhibitors.

Dr. Jon Trent, MD, PhD, and staff for GIST Cancer Research at the University of Miami, Sylvester Comprehensive Cancer Center has been exploring the use of a new medicine for GIST called Procaspase Activating Compound (PAC)-1. PAC-1 is designed to make other drugs more effective.

During the past 10 years, Sylvester Comprehensive Cancer Center’s Sarcoma Program has developed into the largest sarcoma center in the southeastern United States. With more than 20 dedicated, multidisciplinary, board-certified sarcoma doctors on staff, Sylvester serves approximately 900 new patients per year.

Download the pdf of Dr. Trent's Impact Report August 2022 for Gastrointestinal Stromal Tumor Research.
Impact 2022 Sarcoma_GIST

Dr. Anette U. Duensing, MD, GIST Cancer Researcher at the University of Pittsburgh Cancer Institute, Reports On Latest Research

Dr. Anette Duensing, GCRF's advisor, Associate Professor of Pathology and member of the Cancer Therapeutics Program at the University of Pittsburgh Cancer Institute gives an update on her latest research on GIST Cancer.

Dr. Meg von Mehren, GCRF's GIST Cancer Advisor and researcher at The Fox Chase Cancer Center, Philadelphia, PA, gives an update on how GCRF has helped their research.

Not only do Fox Chase physicians have extensive experience in diagnosing and treating sarcomas, but they head panels of experts tasked with writing and updating sarcoma treatment guidelines that are used both nationally and globally. They also work with other world-renowned experts to conduct clinical trials, both for early and advanced stage sarcomas.

“When we see a patient with sarcoma, we think about how to best treat them as a team,” said Margaret von Mehren, MD, Chief of the Division of Sarcoma Oncology at Fox Chase. “Our program includes specialists in sarcoma medical oncology, surgical oncology, orthopedic surgical oncology, radiation oncology, radiology and pathology who review tumor biopsies and imaging to determine the best possible treatment for each case.”


Watch the presentation by Dr. Cristina R. Antonescu and Dr. Ping Chi on their ongoing, joint research for GIST Cancer at Memorial Sloan Kettering Cancer Center.

In 2012, The GIST Cancer Research Fund and Robert and Tania Stutman were honored by Memorial Sloan Kettering Cancer Center for GCRF’s generous donations given for GIST Cancer Research. Their names were etched into MSKCC’s donor wall for posterity. For almost twenty years, The GIST Cancer Research Fund has been tirelessly fighting to raise funds to eradicate this deadly disease with no staff, corporate headquarters or overhead. Since 2002, the foundation has raised more than $10 million and MSK has been the beneficiary of $1.6 million. Events including walkathons, 1,000-mile Cycling for a Cure bike rides, golf outings and galas now span the nation. (Other GCRF beneficiaries include Fox Chase, Brigham and Women’s Hospital in Boston, Oregon Health Sciences University Cancer Institute, and MD Anderson Cancer Center in Houston.) At MSK, the GCRF supports the work of Dr. Antonescu and Dr. Ping Chi.

Robert and Tania Stutman join the generous philantropists including Susan G. Komen, who donate to MSKCC. The GCRF has raised $10 million dollars for GIST Cancer Research and has given 100% of these fund to finding a cure for GIST Cancer. As Tania Stutman said, ‘I’m not only battling for my life, I’m fighting for the lives of others.’”

A Message From Dr. Jonathan Fletcher

Dr. Jonathan Fletcher, GCRF's GIST Cancer Advisor and researcher at Brigham and Women's Hospital in Boston, Massachusetts and members of the Fletcher Lab give a message of hope as well as updates on their GIST Cancer research. Thank you Dr. Fletcher and Lab members for all that you have contributed to the fight for a cure of GIST Cancer.

Thank You Dr. Mike Heinrich and the Heinrich Lab For Walking For A Cure In Portland, Oregon

The GCRF is a GIST patient-run non-profit (501(c)(3)) that has supported the GIST basic research being performed in the laboratory of Dr. Michael Heinrich* here at OHSU, as well as numerous other GIST research programs around the United States, for nearly two decades. The funds donated to research from the GCRF fund research for improving the care of GIST patients. Without the support of the GCRF, the immense progress that has been made in improving GIST patient care at OHSU would not have been possible.

 

*Dr. Mike Heindrick has pledged to match all donations made from our participants.*

 

Dr. Michael C. Heinrich, one of GCRF's GIST Cancer Advisors and researcher at The OHSU Knight Cancer Institute in Portland, Oregon, gives an update of his work and progress of finding a cure for GIST.

In Memory of My Aunt, Stephanie Kalenda

Stephanie (Teta) Kalenda had GIST cancer. Like so many patients, she fought a valiant fight against this disease and yet lost her life.  Her niece, Jamela, decided to start a small fundraiser beginning on July 12, GIST Awareness Day in memory of her Teta, who would have been 64 years old. She was looking for 64 donations. While she didn't make the goal, she still raised over $1700. for GIST Cancer Research. This young woman is making a difference in the fight for a cure of GIST Cancer. She made a stand and took action so that one day, there will be cure of this terrible disease.

One behalf of all of us at GCRF, thank you Jamela! Your Teta will always be remembered and loved.

Walt Frazier is a two-time NBA champion with the New York Knicks, a seven-time NBA All-Star and a member of the Basketball Hall of Fame. His retired No. 10 Knicks jersey is hanging in the rafters in Madison Square Garden. The NBA veteran is also known to be the GCRF's very own spokesperson. Walt has attended the GCRF New York Walk For A Cure for 18 years. His loyalty and commitment to GIST Cancer Research is relentless and he always finds the time to "be there" for the GIST Cancer Research Fund in good times and bad. Thank you Walt for all you have done and know that we hold a special place for you in our hearts!

A look behind the scenes in the lab of Dr. Michael Heinrich and Dr. Chris Corless at the Oregon Health & Science Center/Knight Cancer Institute. Here is an overview of the current research being performed to find a cure for GIST Cancer.

“I started with just a little website,” Tania says. “I went on local radio. I went to our local paper and told them my story.” In 2001, she held her first walkathon and raised $23,000. In 2018, the foundation has raised more than $10 million dollars and every penny has gone to GIST Cancer Research.

United States Senator, Charles “Chuck” Schumer graciously acknowledged the GIST Cancer Research Fund with a proclamation for the importance of the numerous contributions that the GIST Cancer Research Fund and the Walk For A Cure has made to find a cure for GIST Cancer.

GIST is a rare form of cancer that most doctors misdiagnose or are not familiar with the appropriate treatment. If you or a loved-one is diagnosed with GIST, getting in touch with a physician who specializes in GIST Cancer is of utmost importance. These doctors and researchers deal with this disease on a daily basis and can help guide you to the right treatment.

In addition to the GIST Cancer Research Team of physicians, researchers and nurses, the following link will put you in touch with domestic and international GIST Cancer specialists.