Tracking Sarcoma Response and Resistance to Radiation Therapy
Abstract
Soft tissue sarcomas are a group of cancers that arise from muscles, fat, blood vessels, and other connective tissues throughout the body. These cancers are typically treated with surgery and radiation therapy to control the cancer in its original location, but soft tissue sarcomas have a propensity to spread to other organs of the body. In addition, these tumors are often resistant to radiation therapy, and recurrences at the site of prior radiation therapy are challenging to salvage. As a result, markers to identify patients at risk of developing cancer spread to other organs of the body or recurrences at the site of prior radiation therapy are urgently needed. The proposed project aims to utilize DNA released from soft tissue sarcomas into the bloodstream, called circulating tumor DNA, as a marker of how patients are responding to treatment. In addition, we hope to use circulating tumor DNA to identify DNA mutations within soft tissue sarcomas that explain why some tumors respond favorably to radiation therapy while other tumors ultimately grow back. These studies have the potential to enable personalized treatment approaches based on the biology of each patient s tumor to improve survival while minimizing toxicity. Dr. Everett Moding, the Principal Investigator (PI), is physician scientist at Stanford University who specializes in the research and treatment of patients with sarcomas. He hopes to develop a translational research program utilizing analysis of human samples and detailed experiments using cell and mouse models to improve sarcoma treatments. This Career Development Award will provide mentorship, research time protected from clinical care responsibilities, and crucial research funding to advance Dr. Moding s career in the area of sarcoma research. Specifically, the dedicated training and hands-on experience will enable Dr. Moding to establish the technical and computational approaches necessary to implement circulating tumor DNA as a marker in patients with soft tissue sarcoma and develop the cell and mouse models for his future experiments. Soft tissue sarcomas occur at any age and affect men and woman of all racial and ethnic groups. The proposed research could help to identify patients with localized soft tissue sarcomas who may benefit from more intense treatment because (1) they are unlikely to respond to standard radiation therapy, or (2) they are at high risk of their cancer spreading to other organs. In the short-term, this project will identify predictors of relapse and improve our understanding of soft tissue sarcoma biology. In the long-term, this study will lay the groundwork for clinical trials testing personalized treatment approaches based on soft tissue sarcoma genetic factors and circulating tumor DNA analysis. This research addresses the Fiscal Year 2021 Peer Reviewed Cancer Research Program Overarching Challenges: (1) Develop strategies and biomarkers to predict cancer risk, treatment resistance, recurrence, and advanced disease to mitigate risk in target populations, and (2) Develop minimally invasive methods to detect cancer initiation, recurrence, and progression. This project will establish a minimally invasive biomarker for soft tissue sarcomas and identify soft tissue sarcoma genetic factors that predict resistance to radiation therapy. Due to the potential contribution of military-related exposures to their development, the cost associated with their treatment, and their potential to cause loss of limb function and death, soft tissue sarcomas are a critical challenge for military health. The proposed research will benefit active-duty Service Members, Veterans, and other military beneficiaries who develop soft tissue sarcomas by improving our ability to predict which patients will develop recurrent disease. Furthermore, this project could lead to the development of new treatments that improve survival and minimize side effects.
Document Details
- Document Type
- DoD Grant Award
- Publication Date
- Dec 28, 2022
- Source ID
- W81XWH2210161
Entities
People
- Everett J Moding
Organizations
- Stanford University
- United States Army