Molecular Mechanisms of Response and Resistance to Immunotherapy in Mesothelioma
Abstract
Malignant pleural mesothelioma is a lethal malignancy associated with a dismal prognosis, and it has a much higher incidence in Veterans relative to the general population. The advent of new therapies that recruit the immune system to target and destroy cancer, referred to as immunotherapy, is expanding the therapeutic options for patients with mesothelioma. The Food and Drug Administration has granted breakthrough therapy designation across seven different indications to multiple immunotherapy, leading to a paradigm shift in therapeutic approaches for thousands of patients. The principal investigators of this proposal have led clinical trials that combine immunotherapy with chemotherapy for patients with mesothelioma and these trials have shown promising results. While the encouraging clinical efficacy of immunotherapy is compelling, considering the increased cost to patients and health systems both financially and in terms of time spent in management of immune-related adverse effects, it has become clear that success of immunotherapy approaches depends on choosing patient populations most likely to benefit. In this proposal we seek to understand the genetic wiring of response and resistance to chemo-immunotherapy in patients with mesothelioma, employing in-depth analyses of tumor and immune cells. We propose to use clinical samples from four novel clinical trials that combine chemotherapy and immunotherapy and develop robust predictive biomarker platforms. In parallel, we will employ liquid biopsies, which are noninvasive approaches that capture genetic material released into the bloodstream when tumor cells die. Liquid biopsies are particularly informative in the setting of immunotherapy, where imaging fails to capture therapeutic responses. We aim to combine liquid biopsies with changes in immune cells in the blood to generate non-invasive ways to predict response to chemo-immunotherapy in mesothelioma. We believe that our comprehensive, cutting-edge scientific approach, linked with ongoing or soon-to-start clinical trials will result in immediate clinical intervention initiatives and is consistent with our mission to deliver improved treatments to patients with mesothelioma. Our scope of work, focusing on the intersecting fields of immunotherapy and mesothelioma is in line with the Fiscal Year 2019 Peer Reviewed Cancer Research Program Focus Areas and has the ultimate goal of tailoring therapies and improving outcomes for military members, Veterans and the general public.
Document Details
- Document Type
- DoD Grant Award
- Publication Date
- Mar 10, 2021
- Source ID
- W81XWH2010638
Entities
People
- Valsamo Anagnostou
Organizations
- Johns Hopkins University
- United States Army