Exploring the Regulatory Landscape of Pediatric vs Adult Germ Cell Tumors in a Developmental Framework to Gain New Therapeutic Insights
Abstract
Germ cell tumors (GCT) an fiscal year 2022 (FY22) Peer Reviewed Cancer Research Program (PRCRP) Topic Area, best known to the lay public as testicular cancer, are the most common solid tumor in adolescents and young adults, a second FY22 PRCRP Topic Area. This proposal addresses the gaps in cancer research concerning diagnosis, prognosis, and treatment of GCT that are decreasing mission-readiness. Our objectives are to discover more accurate ways to predict risk of recurrence, based on genomics and computer-informed digital pathology (diagnosis and prognosis), and to discover new types of treatment that can replace the effective, but highly toxic, current mainstay of treatment, cisplatin. Most prior research has focused on testicular cancer, as it is the most common manifestation of GCT. But GCTs also arise throughout childhood, from infancy to adolescence, and in women as well as men. Broadening our investigations to include all ages and both genders is motivated not only by biologic rationale, but also to redress the understudy of children and women with GCT. This broad scope is responsive to one of the FY22 PRCRP. Overarching Challenges: Distinguish unique features driving cancer occurrence across the spectrum of ages. Given the population to be studied include children and adults, men and women, the proposed research in the most common solid tumor between the ages 15-40 years, has the potential to benefit all active-duty Service Members and their beneficiaries. This proposal also addresses several of the other FY22 PRCRP Overarching Challenges in the categories of Prognostics and Therapeutics such as: Identify strategies to predict treatment resistance, recurrence, and the development of advanced disease; Transform cancer treatment through the identification of new targets, especially for advanced disease and metastasis; Identify and elucidate the mechanisms behind cancer epigenetics/genetics and cancer development to improve treatment method. We expect the near-term benefits to patients to include: more accurate diagnosis of GCT using computer vision analysis of digitized pathology slides, more accurate prognostication of GCT using both the histologic features identified by computer vision analysis, as well as the new molecular signatures of chemoresistance we discover, better understanding of how any prognostic markers identified also applies to children, AYA, and to women, not just to adult men, and identification of new therapeutic options, including confirmation of the efficacy of WNT inhibition, to test in both standard risk, poor risk, and relapsed disease. This broad approach is possible in part due to a decade-long collaboration among pediatric, gynecologic, and genitourinary oncologists and scientists fostered by the Malignant Germ Cell International Consortium (MaGIC), a group of the leading experts in GCT from 15 countries that have jointly published over 50 manuscripts and have three international National Cancer Institute-funded clinical trials underway. As a consequence of this collaboration, we have been able to create the largest collection of clinically annotated GCT biospecimens that we are aware of with which to perform our proposed analyses. Lack of access to biospecimens has been a major obstacle to research in the past. We will also have the ability to validate our findings in the biospecimen banks of other MaGIC members (e.g., University of Southern California, Cambridge UK, Graz, Austria), as well as to prospectively evaluate both new ways to risk stratify and test new drugs/therapeutics in clinical trials currently under development by MaGIC. Two new clinical trial concepts designed by MaGIC have recently been approved by the National Cancer Institute; prospective validation therefore of any of our discoveries could become part of the secondary aims of the new trials under development. Because of MaGIC, we can more quickly facilitate the translation from basic biolo
Document Details
- Document Type
- DoD Grant Award
- Publication Date
- Jan 04, 2024
- Source ID
- HT94252310604
Entities
People
- Anne Frazier
Organizations
- Dana–Farber Cancer Institute
- United States Army