The GIST Cancer Awareness Foundation held a Patient Forum on May 6th, 2013 at the Rockefeller Research Laboratories of Memorial Sloan-Kettering Cancer Center. The aim of the Forum was to educate patients, survivors, family members and supporters on the latest advances in understanding and treating GIST.

Four members of the Memorial Sloan-Kettering faculty presented: William Tap, MD, Section Chief, Sarcoma Oncology in the Melanoma and Sarcoma Service; Richard Carvajal, MD, Assistant Attending in the Melanoma and Sarcoma Service; Ronald DeMatteo, MD, Vice Chair, Department of Surgery; and Ping Chi, MD, PhD, Assistant Attending in the Melanoma and Sarcoma Service and member, Human Oncology and Pathogenesis Program. Dr. Chi was the recipient of a grant from the GIST Cancer Awareness Foundation in 2012.

Dr. Tap began the Forum with an overview of GIST, its current treatment options, and the challenge it poses to clinicians and researchers. Importantly, he discussed why many patients treated for advanced GIST with imatinib (Gleevec) will eventually become resistant to the drug. Imatinib is designed to target a specific mutation in a surface cell receptor known as KIT. This mutation causes KIT to bombard cells with the signal to proliferate, which drives tumor growth. Imatinib inactivates this rogue signal by binding to the mutated receptor and regulating cell growth. Patients who develop resistance to imatinib often develop a new, secondary mutation that circumvents the target of the drug.

But, KIT remains an attractive target in the treatment of GIST. Now, research is focused on designing strategies that will leverage this existing benefit by adding other drugs to enhance the antitumor immune system response and prevent resistance.

Drs. Carvajal and DeMatteo discussed a new Phase I clinical trial led by Memorial Sloan-Kettering that aims to do exactly that. The new trial combines dasatinib (Sprycel), a leukemia drug that targets both KIT and the pathway IDO, with the recently approved melanoma drug ipilumumab (Yervoy). Ipilimumab targets the receptor CTLA-4 and stimulates the immune system to recognize and destroy cancerous cells. Although both drugs are approved, a Phase I trial is necessary to test for safety and proper dose. Once the optimal dose is determined, a Phase II trial will determine its efficacy in treating patients who have become resistant to imatinib.

Finally, Dr. Chi spoke of her work in developing the next generation of targeted drugs for GIST and other sarcomas. Her laboratory is focused on finding novel diagnostic and prognostic biomarkers –and then designing new therapies to target them. For example, the Chi laboratory recently identified a new biomarker – ETV1 – that they believe is required for the development, growth and survival of GIST. The laboratory is now focused on 1) elucidating the genetic and epigenetic mechanisms of the gene; and 2) characterizing the molecular mechanisms of the ETV1 protein so as to develop novel strategies to target the mutation.

Importantly, Dr. Chi believes ETV1 targeted-therapy in combination with imatinib could prove more effective that imatinib (Gleevec) alone. She hopes that this work will be ready to begin the clinical trial process later this year.

No Excuses University
True story…a 2nd grade student at our NEU at David Weir Elementary in Fairfield, CA brought a paper bag full of money to his Principal. He told her he was saving money for a long time because he wanted to buy a Nintendo 3DS. But, he said instead of keeping the money for his DS he wanted to donate the money to his sch…ool’s fundraiser for GCAF. He said his friend’s Mom passed away from cancer and he wanted the money to help someone. This young man put his own interests aside, hoping the money he saved could make a difference for someone else. This student is AWESOME!!!

This forum is open to GIST patients and caregivers who have an interest in learning more about GIST. The GIST Patient Forum is a great opportunity to hear from the experts on the latest developments in regards to treatment
and research. A question and answer session will follow the presentation.

We have availability for 30 participants so please reserve your seat by confirming your attendance to Barbara Livermore via email barbara@gistawareness.org or Dorothy McBride at dorothy@gistawareness.org.

Topics that will be covered: pediatric GIST; surgical procedures/outcomes; current clinical trials; and therapeutic treatments.

Speakers from MSKCC:

Dr. Tap
Dr. Chi
Dr. Carvajal
Dr. DeMatteo

Will hope to see you on the 6th.

Meeting location:

MSKCC
Rockefeller Research Lab
430 East 67th Street
New York, NY

NY State Assemlyman Joseph Borelli had the New York State Assembly pass a legislative resolution proclaiming April 6th, 2013 as Gastrointestinal Stromal Tumor Awareness Day in New York State.

New York State Senator Donna Savino issued a proclamation recognizing the GIST Cancer Awareness Foundation

United States Congressman Michael Grimm issued a Certificate of Special Congressional Recognition to the GIST Cancer Awareness Foundation.

Dr. Mrinal Gounder of Memorial Sloan Kettering Cancer Center provided the attendees with an overview of GIST and stressed the importance of grass roots programs such as ours that raise much needed funds for research.

We want to thank all of the guests who helped make the dinner a success and all of the local merchants that contributed to our raffles.

Please join us on the 6th to help raise awareness of GIST and to raise money for an important cause.

If you would like to buy tickets, please contact Dorothy McBride at dorothy@gistawareness.org or call 718-966-7125.

The support from the NEU network continues with fundraising initiatives by Washington Terrace Elementary School; Karshner Elementary; Winchester Elementary; John Tibbott Elementary; Luepp Public School; Magnolia Independent School District; and Mitz Bond PTA.

We appreciate the dedication of the NEU schools and thank you all for your great fundraising efforts.

The following people have donated in memory of Kevin:

Mr & Mrs Brad Hodges
Paula Rogers
Jerry & Cheryl West
Judith Cevtetic
Davidson Family
Spivey Family
Erica Parr
Edward Braden
John Rogers

Our sincere condolences to Kevin’s mother, Eleanor Schilling and the friends and family of Kevin.

GCAF appreciates the Moon Family selecting us to receive donations in memory of Kevin.

The deadline for submitting a proposal is January 31st, 2013.

Please follow the instructions “How to Apply for a Grant” on our website.

Our third annual Trucking for GIST event was held during the week of September 17th with our host trucking company, Marine Transport of Mountainside, New Jersey.

133 drivers participated in the week long event in which they proudly wore GIST Cancer Awareness Foundation/GIST Support International bracelets and handing out over 300 GCAF brochures to help raise awareness of Sarcomas and specifically, GIST.

The Marine Transport drivers logged over 184,000 miles during the week and handed out brochures in New Jersey, New York, Connecticut, Rhode Island, Massachusetts, Pennsylvania, Ohio, Indiana, Illinois, Wisconsin, Michigan, Delaware, Maryland, Virginia, West Virginia, North Carolina, South Carolina, Georgia and Alabama.

In addition to increasing awareness of GIST, this event raised $ 36,000 for the GCAF grant program.

We want to thank Robert Castelo, President of Marine Transport and his management team for their wonderful support and especially the 133 drivers who have helped spread the word about GIST

Dr. Chi will use the $ 50,000 grant award in relation to her study on Understanding and Targeting ETV1 in Gastrointestinal Stromal Tumor.

We are excited about Dr. Chi’s work and the positive results that will aid GIST research.

The GCAF Board thanks our Science Team for their continued excellent work in reviewing grant proposals.

view photos from this event

Lay Abstract:

Gastrointestinal stromal tumor (GIST) is one of the most common types of human sarcomas, arising from the interstitial cells of Cajal (ICCs). The majority of GISTs harbor activating KIT mutations, which is thought to be the main oncogenic “driver” in GIST pathogenesis. Despite the effectiveness of Imatinib-a KIT-specific receptor tyrosine kinase inhibitor (TKI), resistance to TKI invariably develops and it is imperative to better understand the pathogenesis of GIST and to identify novel therapeutic targets.

We have recently discovered that ETV1, an ETS family transcription factor implicated in the pathogenesis of other malignancies including prostate cancer, is a master regulator of a transcriptional program that characterizes cells belonging to the ICC-GIST lineage and is required for their maintenance and survival. We further show that ETV1 regulates the GIST-signature genes and mutant KIT strongly cooperates with ETV1 in GIST tumorigenesis at least in part by stabilizing ETV1 protein levels.

Our findings suggest that ETV1 may define the optimal cellular context for mutant KIT-driven oncogenesis, and provide a rationale for why patients and mice with germ-line activating-KIT mutations exclusively develop neoplasia (GIST) of the ICC-lineage, but not of other KIT-regulated cell lineages (i.e., melanocytes, germ cells and hematopoietic stem cells). These observations led to the proposed studies to further characterize the genetic and epigenetic mechanisms involved in the regulation of the oncogenic ETV1-dependent transcriptome, to dissect the mechanisms of ETV1 protein stability regulation downstream of KIT/MAP kinase pathways, and to uncover novel therapeutic strategies that target ETV1 protein stability and transcriptional activity in GIST.

These studies will provide a comprehensive understanding of the pathogenesis of GIST mediated by the ETV1-dependent transcriptional program and can have broad implications on other ETS transcription factor dependent malignancies. Importantly, it will provide novel therapeutic strategies for imatinib-resistant GIST and likely other ETV1-dependent malignancies.