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The OSI Announces 2022 Grant Recipients

A leading funder of osteosarcoma research awards a total of $1 million to two groundbreaking research projects.

The Osteosarcoma Institute (OSI) — a leading funder of osteosarcoma research — is pleased to announce its 2022 research grant funding recipients. Out of 25 applications submitted in the 2021-2022 grant cycle, the OSI’s expert review committee selected two potentially groundbreaking scientific research projects.

“This year, we selected two novel research studies to receive $500,000 each,” says Lee Helman, MD, the OSI’s Director and an expert in the field of osteosarcoma. Since its inception in 2017, the OSI has awarded more than $5 million to cutting-edge osteosarcoma research. Funding research is an early step toward developing better treatments, and ultimately, a cure. The standard treatments for osteosarcoma have not changed in 40 years. New kinds of therapies are critical to saving lives.

“These are two promising studies that are led by exemplary scientists. I am eager and excited to see what data unfolds.” — Lee Helman, MD, OSI’s Director

The Frontline spoke with Dr. Helman to understand more about the winning cancer research projects.

Improving Therapy by Combining Drugs

Jason Yustein, MD, PhD, of Emory University’s Winship Cancer Institute, submitted a winning proposal titled, “Use of combination therapies to improve immune-mediated approaches for high-risk osteosarcoma.”

Dr. Yustein’s study will evaluate combining two approaches to osteosarcoma therapy that may work together synergistically: immunotherapy, which utilizes the immune system to attack cancer cells, and targeted therapy that specifically blocks signals that are needed for the growth of cancer cells. The studies will be conducted in mouse osteosarcoma tumors that are believed to closely resemble human osteosarcoma. If the results show promise, the next step would be to test the most promising combinations in clinical trials in patients with osteosarcoma.

Combining immunotherapy and targeted therapy allows immune cells to kill cancer cells

It is believed that drug combinations may be more effective than a single “silver bullet” drug to treat osteosarcoma. That is why Dr. Yustein is looking at broad combinations of therapies.

“This project has the potential to affect primary tumor growth and provide new treatment options for patients,” says Dr. Helman. “If successful, we expect to have pre-clinical data and rationale to move this into clinical trials, where the drugs can be tested in human participants.”

Activating a Novel Aspect of the Body’s Immune Response

Alejandro Sweet-Cordero, MD, of the University of California, San Francisco, submitted a proposal titled, “Activation of STING as a therapeutic strategy in treating osteosarcoma.” Dr. Sweet-Cordero is pictured above (front row in light blue) with members of his lab.

Shorthand for “stimulator of interferon genes,” STING is feature of the immune system: a sensor that triggers an immune, cell-killing response. Dr. Sweet-Cordero’s research, using mouse models, aims to discover if something about osteosarcoma can be used to activate this pathway.

blocking the ENPP1 enzyme could free up the STING pathway to stimulate an immune response

One of the hallmarks of osteosarcoma is that its chromosomes, which hold the cell’s DNA, are “mixed up,” explains Dr. Helman. This is called chromosomal instability, which has been shown to lead to DNA outside the cell nucleus (called cystolic DNA). This is important because cystolic DNA should trigger the STING pathway.

However, STING is typically inhibited by an enzyme called ENPP1. Dr. Cordero has preliminary data suggesting this enzyme is highly active in osteosarcoma tumors. This suggests that blocking the ENPP1 enzyme could free up the STING pathway to stimulate an immune response that could hopefully be used to treat osteosarcoma patients.

“This is a very novel approach,” says Dr. Helman. “It essentially uses osteosarcoma’s chromosomal instability as an Achilles’ heel of sorts to stop tumor growth and spread. It is preliminary but it is very exciting because it is a completely different approach.”

Using the Research to Benefit Patients

Dr. Yustein and Dr. Sweet-Cordero will provide a progress report every six months to be shared with the OSI Strategic Advisory Board. Upon completion of the studies, the results will be available to the public and will be used to inform future efforts aimed at new treatment options for osteosarcoma.

“I believe these two studies will vastly improve our understanding about osteosarcoma,” says Dr. Helman. “They are led by exemplary scientists. I’m eager and excited to see what data unfolds.”

The end goal of this research is to dramatically increase treatment options and survival rates in osteosarcoma patients.

“The more we understand about osteosarcoma, the more we can tailor treatment to meet each individual patient where they are at on their cancer journey,” says Dr. Helman. “We have no other option but to think differently when it comes to this devastating cancer.”

The Osteosarcoma Institute is one of the leading funders of osteosarcoma research. To apply for funding for clinical trials, correlative studies, or translational studies, see more information on the OSI’s grant program or inquire about “off-cycle” grant funding.

If you are a patient, family, or foundation interested in co-funding research with the Osteosarcoma Institute, please email giving@osinst.org.

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