MCCB student Kat Murphy awarded NIH fellowship to advance novel therapeutic strategies for aggressive prostate cancer

Kat Murphy, a PhD student in the lab of Marcus Ruscetti, PhD, has received an NIH predoctoral training fellowship from the National Cancer Institute (NCI) to fund her studies identifying and targeting the genetic determinants of immune suppression and immunotherapy failure in prostate cancer.

Murphy’s research centers on neuroendocrine prostate cancer (NEPC), a highly aggressive form of prostate cancer that can develop in the later stages of the disease following hormone therapy failure. NEPC has a poor prognosis and limited treatment options. Interestingly, a subset of NEPC patient tumors are “inflamed” with T cells and have elevated expression of interferon gamma (IFNγ), which is typically associated with positive immune checkpoint blockade outcomes, suggesting these patients may benefit from immunotherapy.

But using a novel mouse model of NEPC that she developed—in which three tumor suppressor genes commonly mutated in NEPC patients (Pten, p53 and Rb1) are knocked out in the prostate—Murphy unexpectedly found that the inflamed mouse NEPC tumors failed to respond to immunotherapy. The lack of response appears to be due to elevated levels of macrophages within the tumor microenvironment, which can suppress T cell activity and reduced the effectiveness of immunotherapy.

Murphy will investigate how IFNγ signaling promotes tumor growth and macrophage dysfunction, and test whether blocking IFNγ signaling or macrophage activity can sensitize NEPC tumors to immunotherapy. The results of the study will lead to a better understanding of both the cell-intrinsic and -extrinsic mechanisms driving NEPC, laying the groundwork for developing novel therapeutic strategies to treat this aggressive disease.

Read the related story from UMass Chan News.