Figure 1. The combination of Gemcitabine & AZD1775 makes pancreatic cancer cells more sensitive to radiation. Cultured pancreatic cancer cells were treated with radiation, either drug + radiation, or both drugs + radiation. Fewer cells survived with the combination of all 3 agents.
Cancer cells depend on DNA damage response pathways for survival following treatment with chemoradiation therapy. Dr. Morgan’s laboratory has pioneered the use of drugs which inhibit the DNA damage response to sensitize tumors cells to chemoradiation therapy. AZD1775 is a selective inhibitor of the WEE1 kinase which inhibits the DNA damage response and sensitizes pancreatic cancer cells (Fig. 1) and tumors to chemoradiation. In 2014 these promising laboratory studies were translated to a phase 1 clinical trial led by Drs. Cuneo and Lawrence in which patients with locally advanced pancreatic cancer are treated with AZD1775 and chemoradiation. As part of this trial, hair follicles (Fig. 2) and circulating tumor cell biopsies are being used to evaluate patient responses to therapy. This trial is currently still open for patient accrual. The ultimate goal of these studies is to improve outcomes and survival in pancreatic cancer patients.
In this collaboration with Dr. Sunitha Nagrath in the Department of Chemical Engineering, Drs. Morgan and Cuneo are studying ways of assessing drug effects on tumor cells circulating in the blood. These cells can be isolated using a device developed in Dr. Nagrath's lab, and an example is shown in Figure 2 (right).