Project Summary/Abstract Gynecologic Cancer remains an underfunded area of research with funding to lethality scores significantly lower than other cancer sites. Endometrial cancer, the most common gynecologic cancer, is one of the few cancers that has seen an increase in incidence and mortality over the recent years, with black women and minorities disproportionally affected. Underrepresented populations often develop high risk and rare subtypes of uterine cancers with distinct molecular profiles. Recent research has identified several molecular subtypes that can be targeted with novel agents, however, most of these studies have low enrollment of underrepresented populations who are most likely to have the greatest benefit. Molecularly driven trials are critical to the progress of personalized medicine to improve survival and limit exposure to ineffective therapy and associated toxicities. Unfortunately, these highly specialized clinical trials are at risk of failure due to slow accrual or under-enrollment of the appropriate populations. As the national PI for NCI/NRG-GY020 (vaginal brachytherapy +/- immunotherapy for early stage high risk mismatch repair deficient endometrial cancer, which is a subset of endometrial cancer patients who are highly sensitive to immunotherapy) Dr. Backes is well aware of the opportunities and challenges associated with molecularly driven clinical trials. NCI support through the R50 mechanism will allow Dr. Backes to increase her efforts to improve enrollment to clinical trials for all populations, both at her institution and nationally. First, leveraging the resources of the Ohio State University Comprehensive Cancer Center (OSUCCC), Dr. Backes will develop a comprehensive system for molecular matching to simplify and streamline the identification of patients for trials and specialized trials for patients, which will increase accrual. Collaborative cross-disciplinary efforts are especially important with the increasing complexity of molecularly driven clinical trials, such as NCI ComboMatch and iMatch, and also to improve the outcomes of patients with rare tumor mutations. Secondly, Dr. Backes will collaborate with Dr. Elektra Paskett to include gynecologic oncology on a recently opened study “OSU Connecting Underrepresented Populations to Clinical Trials” (1U01CA274999-01). Dr. Backes and Dr. Ashley Felix (PhD, Epidemiology) will focus on assessing barriers and implement strategies to improve access to care and clinical trials for underrepresented populations in gynecologic oncology locally and nationally. Finally, the opportunities afforded by this award will allow Dr. Backes to increase her time to design and support the development of paradigm shifting clinical trials, and mentor junior investigators in this process, through her national roles as the NRG Oncology Co-Chair for Developmental Therapeutics, member of the Uterine Corpus Committee, New Investigator Committee, NCI Uterine Taskforce, national PI for N...