Targeting the Oncoprotein RLIP as Novel Therapy for Melanoma
Abstract
Melanoma is a highly invasive and chemo-resistant tumor for which no effective therapy is available. The current treatment options for advanced melanoma do not induce complete cure and the 5-year mortality is 80%. Hence, the development of novel targeted therapy assumes immense translational significance in contemporary melanoma research. Our findings are of fundamental mechanistic importance to the understanding of the causes of carcinogenesis and drug/radiation resistance. They apply broadly to cancer, not only to specific histologies or mutations. A broad-spectrum therapy of cancer that targets fundamental etiological mechanisms is highly relevant to human health, given that cancer is the second leading cause of death. Optimization of the novel compound “RLIP-antisense” will lead to composition patents, followed by clinical translation through institutional, granting agencies, pharmaceutical industry, and venture capital. This project is of noteworthy clinical importance, with potential for both the general public and military Service members. The research proposed in this application directly addresses the Fiscal Year 2019 Melanoma Research Program Focus Area: “Therapeutic Prevention.” Melanoma is the 6th most common cancer for men and the 7th for women (4% of all cancer cases) in the United States. Melanoma diagnosis in patients with significant sun exposure, such as military personnel, is often complicated by the frequent occurrence of atypical nevi in sun-exposed skin. Melanoma, one of the most lethal forms of skin cancer, remains resistant to available treatments. Therefore, additional target-based approaches are needed for the management of this neoplasm. This proposal directly addresses one of the most challenging Focus Area – assessment of militarily relevant risk factors (e.g., radiation, chemical, and environmental carcinogens) associated with the susceptibility, early detection, progression, and treatment of melanoma. Our study is relevant to the health and welfare of current Service members, their families, and other military beneficiaries, including Veterans. The studies have relevance to Warfighters’ future health and to future US Department of Veterans Affairs costs. We believe that the present proposal would be “the first of its kind investigation” in testing the mechanisms contributing to melanocyte transformation and metastatic progression as a function of RLIP expression, with a focused mechanistic relevance to signaling networks of specific importance in melanoma. Our proposed studies should delineate how the RLIP-targeted therapy exerts its potent anticancer effects in melanoma and lay the foundation for future development in targeting malignant melanoma, thereby filling a critical void in the effective clinical management of malignant melanoma. Ultimate Applicability The proposed RLIP-targeted method of treatment will help patients in remission after treatment of localized or metastatic disease. RLIP-targeting strategy is particularly attractive against melanoma. As described, we believe the research is not primarily basic and that a direct clinical application is quite feasible. The goal of any targeted therapy to treat human malignancies essentially relies on the potential of the intended drug candidate to survive through multiple stages of drug development. The overall impact is to improve the length and quality of life of patient with metastatic melanoma, and it will be further enhanced by City of Hope’s status as an “NCI-Designated Comprehensive Cancer Center” with unique facilities for manufacturing novel therapeutics and bringing them to clinical trials on site, allowing us to rapidly translate our findings and impact clinical care.
Document Details
- Document Type
- DoD Grant Award
- Publication Date
- Mar 10, 2021
- Source ID
- W81XWH2010362
Entities
People
- Sharad S Singhal
Organizations
- Beckman Research Institute of City of Hope
- United States Army