David G. DeNardo, PhD
Department of Medicine/Immunology, Washington University in St. Louis
Targeting Cancer Stem Cells By Modulating Immune Responses
targeting cancer stem cells by modulating immune responses
As you likely know, the prognosis for pancreatic cancer patients is very poor with a 5-year survival rate of less than 6%. This is in part due to the propensity of this cancer type for metastatic spread and resistance to therapy. Thus, there is a significant need for new effective treatments for pancreatic cancer and we believe we have identified one. We have recently tested inhibition of CSF1R in pancreatic cancer models and found that this significantly improves responses to chemotherapy and extended survival in mice. To our surprise, we found that this immunomodulatory approach also depletes cancer stem cells. Cancer stem cells are a unique subset of malignant cells that are exquisitely equipped to survive chemotherapeutic treatments. Thus, we’ve shown that by modulating innate immune responses we can target cancer stem cells for destruction by chemotherapy.
From here, we are extending these studies in 3 directions. The first is to test targeting CSF1R in metastatic pancreatic cancer models. This is critical, as 80% of pancreatic cancer patients have non-local or metastatic disease at the time of diagnosis. My laboratory has collaborated with clinicians here at Washington University’s Siteman Cancer Center to design these studies, such that if successful they can be immediately translated into new clinic trials. Thus, we are extremely excited for this possibility. In addition to this, we are trying to better understand the molecular mechanisms by which immune responses regulate the frequency of cancer stem cells. We feel this approach could lead to even more therapeutic targets for us to exploit. And lastly, since targeting innate immune responses through CSF1R overcomes immune suppression, we are testing this approach to improve immunotherapy. In summary, my research seeks to exploit immune responses to target pancreatic cancer stem cells and thus overcome therapeutic resistance and improve survival in patients.
Young Investigator Award Presentation: Video
David G. DeNardo, PhD
Fall Interim Report
2012 Young Investigator Award - 2013 Interim Report