Grant: CIHR Fellowship

The spread of tumor cells to distant sites leading to metastasis is a common and lethal manifestation of many cancers. Therapeutic strategies for treating metastatic disease primarily rely on DNA-damaging agents, such as chemotherapeutics or ionizing radiation. While initial responses are often observed, resistance to these treatments is almost universal. Recent studies have demonstrated that benign cells in close proximity to tumor cells are key regulators of cancer responses to therapy through the activation of a DNA-damage secretory program (DDSP). The DDSP comprises a diverse spectrum of growth factors and cytokines that are capable of promoting the survival of tumor cells following cancer-directed treatment. The primary objective of this project is to define the damage responses that occur in in the normal benign cells that reside in the bone microenvironment, a common site of metastatic spread from prostate and breast cancers, and evaluate key damage response factors for their effects on tumor cell resistance to therapy. The long-term objective is to develop approaches to circumvent the pro-survival effects of the DDSP to enhance responses to existing treatments. This project will uncover new molecular events in response to therapy and will lead to a new spectrum of therapeutic strategies to improve the management of prostate cancer and other malignancies that are currently highly resistant to standard treatments.