Year 3

Stem cells are characterized by longevity and self-renewal throughout the lifetime of a tissue or organism and the ability to generate all lineages of a tissue. Pathways involved in stem cell function are commonly dysregulated in cancer. Emerging evidence in leukemias and epithelial cancers suggests that tumors can be maintained by self-renewing cancer stem cells (CSCs), defined functionally by their ability to regenerate tumors. Delineating mechanisms that regulate self-renewal in human CSCs are essential to design new therapeutic strategies to combat cancer. One such regulator of stem/progenitor cell function is cell surface protein Trop2.

We have previously shown that Trop2 is a marker and a new regulator of stem/progenitor activity in the prostate. We have also demonstrated that Trop2 is activated in human prostate cancer but not in the cancer-adjacent benign tissue, suggesting a role for Trop2 activation in tumorigenesis.

We have generated 20 human monoclonal antibodies against Trop2 as potential therapeutic tools to inhibit its function or target cancer stem cells expressing high levels of Trop2. Because Trop2 is overexpressed in many epithelial cancers, we believe that blocking Trop2 signaling or targeting cells expressing elevated levels of Trop2 will be an effective strategy to prevent disease progression not only in the prostate but also in other epithelial cancers.