Modulation of Therapeutic Response

Division Of Clinical Sciences - Nci

Investigators

Linked publications, trials & patents

Abstract

Experiments were conducted from October FY25 to mid-January. The experiments consisted of chemotherapy drugs that have the potential effect of enhancing or protecting radiation treatments. Further, molecular imaging as described above will be of considerable use in determining how radiation with or without chemo drugs operate. The drugs we are using are lactate dehydrogenase (LDHAi), OxPhos (IACS-010759) inhibitor, and K-Ras inhibitors AMG510, and MRTX849 (Adagrasib). LDHAi has considerable toxicity and when added with radiation results in significant radiosensitization in vitro. Interestingly, OxPhos inhibitor when combined with radiation treatment does not provide radiosensitization in vitro; however, when OxPhos is used with tumors in mice there is significant radiosensitization. On the other hand LDHAi when used with tumors in mice is less effective. Our EPRI oxygen imaging device has shown that OxPhos decreases tumor hypoxia and thus increases radiosensitization while LDHAi increases hypoxia, thus decreasing radiosensitization. The decrease in hypoxia by OxPhos is a result in mitochondrial consumption of oxygen. Both of the K-Ras inhibitors (AMG510, and MRTX849) yielded radiation sensitization for both in vitro and in vivo experiments. Various proteins were determined for each drug as well as cell cycle analysis and DNA damage repair. We are in the process of putting together manuscripts of these studies.