Nearly 50% of all cancer patients each year are treated with radiation therapy, either alone or in combination with chemotherapy. In the case of radiation therapy, hypoxia (very low levels of oxygen) is an important cause of radiation resistance or treatment failure. Recent evidence suggests that tumors experiencing brief episodes of hypoxia can also harbor radiation-resistant cancer cells. Of specific interest are cancer cells that are situated close to the oxygen diffusion limit in tumors, a region that experiences fluctuations in oxygen availability due to poorly developed vasculature. It is not known if metabolic adaptations (adaptations to decrease energy expenditure) of these cancer cells to fluctuations in oxygen delivery can help promote radiation resistance. The research goal of this project is to develop a multimodal imaging platform to investigate the relationship between microvascular oxygenation and cellular metabolism, and how this relationship helps promote treatment resistance. This project will build and validate a label-free multimodal imaging platform (a two-photon microscope integrated with a hyperspectral darkfield microscope (TP-HDMI)) to quantitatively visualize the relationship between microvascular oxygenation and cellular metabolism and determine how the relationship between these two hallmarks promotes radiation resistance. Knowledge of these relationships in response to radiation therapy can lead to the development of targeted therapeutics to reverse resistance.
Funding: National Science Foundation (1847347, 2143951)
Relevant Publications:
Spectroscopic investigation of radiation-induced reoxygenation in radiation-resistant tumors
Dadgar S, Rodriguez Troncoso JI, Siegel ER, Griffin RJ, Dings PM, Rajaram N, Neoplasia
Optical imaging approaches to investigating radiation resistance
Dadgar S, Rajaram N. Frontiers in Oncology, Special Section on Radiation Oncology