Biomimetic Nanoparticle-Mediated Delivery of Immunomodulating Nucleic Acids as a Strategy to Anticipate Melanoma Drug Resistance
Abstract
Cancer treatment has been revolutionized in the last 2 decades by targeted approaches (drugs that act on specific cancer vulnerabilities) and immunotherapeutic approaches (drugs that take off the brakes of the immune system), extending thousands of people s lives every year. Melanoma, a type of skin tumor, has been the poster child for targeted therapy and immunotherapy. Nevertheless, most patients still experience upfront or acquired resistance to treatment. As a result, precision medicine has sharply moved toward combination approaches to exploit multiple tumor vulnerabilities simultaneously. However, the efforts to combine targeted and immunotherapy strategies have often revealed a lack of efficacy. Some of the patients showing worst treatment outcomes have baseline low immune response, a status that is described as a cold tumor bed. Interestingly, our work suggests that certain types of targeted therapy can cause the tumors to go cold and might explain some lack of response in treatment approaches and recent trial failures. Our central hypothesis is that the adverse effects of targeted therapy on the immune system must be mitigated to achieve a long-lasting treatment response in melanoma. This project will detail targeted therapy s undesired immunologic effects (Aim 1) and optimize a counteracting strategy (Aim 2). Melanoma incidence is increasing among active-duty Service Members, with the greatest incidence rates in the Air Force, Navy, and Marines, with the Air Force presenting with the highest incidence rate among the branches. As a result, there is a pressing need to develop novel treatment strategies, especially for patients currently showing low response rates and survival percentages. The proposed approach is paradigm-shifting, as it has the potential to develop innovative therapeutic tools to re-wire the tumor microenvironment from cold to hot and tilt the balance in favor of a tumor-eradicating immune response (fiscal year 2022 Melanoma Research Program Focus Area, microenvironment impact on response to therapy). Notably, the project has broad potential applicability as this strategy might be applied to multiple melanoma subtypes and therapeutic strategies where cold tumors are an obstacle to efficacious cancer treatment.
Document Details
- Document Type
- DoD Grant Award
- Publication Date
- Jan 04, 2024
- Source ID
- HT94252310576
Entities
People
- Gabriele Romano
Organizations
- Drexel University
- United States Army