The Role of S-Adenosylmethionine in Protection Against Chemotherapy-Induced Liver Injury
Abstract
Objective/Rationale: Colorectal cancer (CRC) (Peer Reviewed Cancer Research Program Focus Area) is among the most common cancer types in military personnel and Veterans and is being seen with increased frequency in individuals younger than 50 years of age. Complications from CRC, such as development of and progression of metastatic disease, occur frequently. Systemic chemotherapy is the standard of care for metastatic colon cancer, and although it is effective, it has detrimental effects on the liver, frequently preventing surgeons from offering a potentially life-saving operation. Additionally, the effects of chemotherapy can have significant effects on patients, preventing them from being eligible for non-surgical treatments. In those patients who can have an operation, the postoperative complication rates are known to be significantly higher because of the toxicities of chemotherapy. As such, identification of the pathway responsible for chemotherapy-induced liver injury and a novel therapy to prevent toxicity is critical. Additionally, identifying a treatment that may enhance the effect of chemotherapy would be revolutionary for patients with metastatic colorectal cancer. S-adenosylmethionine (SAMe), which is a compound found in the body that is responsible for producing and regulating hormones and maintaining the health of cells, is known to be found in decreased concentrations in patients with liver problems. Further, supplementation with SAMe, is known to improve liver health in these same patients. In the U.S., SAMe is available as an over-the-counter dietary supplement. Previous research has shown that it may have an effect in controlling the growth of metastatic colon cancer. Our preliminary research shows that supplementation with SAMe has helped to reduce the degree of liver toxicity in mice being treated with chemotherapy. Applicability of Research and Benefit to Active Duty Members, Veterans, and Remainder of Military: Chemotherapy-induced liver injury that is frequently observed in patients who are being treated for colon cancer. However, the biologic mechanism by which liver injury develops is not entirely clear. This study attempts to determine the pathway by which a commonly used chemotherapy regimen for metastatic colorectal cancer results in the development and progression of liver injury. Further, this study proposes that the use of a readily available supplement, SAMe, may prevent liver injury and improve the effects of chemotherapy in killing metastatic tumor in the liver, thereby improving outcomes and survival in patients with colorectal cancer. PI Career Goals in Cancer Research The PI’s ultimate goal is to develop into an independently funded surgeon-scientist. During the award period the PI intents to generate high-quality preliminary data which will provide insight into the underlying mechanisms of chemotherapy-induced liver injury and potential protective effects SAMe. These findings will serve as the preliminary data to establish further research aims and support the application for an R01 with a clinical trial in patients with colorectal liver metastases. To develop into an independent cancer surgeon-scientist, the PI will focus on developing additional expertise in basic translational research methodology, statistical analysis, and grant-writing and mentored career development. The Department of Defense award will provide this opportunity. Ultimately, the PI will continue to develop a world class gastrointestinal cancer surgery program with excellence in patient-centered care and operative outcomes. Additionally, the PI will work closely with a liver tumor metastases collaborative group, which studies mechanisms of liver cancer metastasis progression and treatment response, and secure independent NIH-based funding (R01) to support her research.
Document Details
- Document Type
- DoD Grant Award
- Publication Date
- Dec 05, 2021
- Source ID
- W81XWH2110375
Entities
People
- Alexandra Gangi
Organizations
- Cedars-Sinai Medical Center
- United States Army