Self-Seeding and Radiation Therapy: A New Strategy Against Metastatic Prostate Cancer—Preventing Circulating Prostate Cancer Cells from “Re-Seeding” in the Prostate May Change the Behavior of Metastatic Cells

Co-Investigator: Karen Knudsen, PhD–Associate Professor, Department of Cancer Biology and Urology at the Kimmel Cancer Center, Thomas Jefferson University

Co-Investigator: Adam Dicker, MD, PhD–Professor, Chairman of Radiation Oncology, Director of Christine Baxter Research Laboratory for Experimental Cancer Therapies, Co-Director Radiation Research and Translational Biology Program at the Kimmel Cancer Center, Thomas Jefferson University

The mechanism by which prostate cancer metastasizes is not fully understood. The decades-old theory is that prostate cancer cells (the seed) leave the prostate, enter circulation, and invade an environment conducive to growth (the soil) such as lymph nodesand bone. Dr. Dicker proposes to test a new theory of metastasis called self seeding where circulating tumor cells leave distant sites and return to their most desired environment, the prostate, where they are “re-energized” and sent back to circulation to further disseminate. This project will test the possibility that radiation therapy to an intraprostatic tumor in mice will interrupt the metastatic behavior of a distant metastasis by destroying the conditioning provided by the prostate. If successful, this concept can be rapidly translated to the clinic as an anti-metastasis therapeutic strategy.

Progress Report:

Radiation Therapy to Block “Self-Seeding” of Circulating Tumor Cells

Prostate cancer is a devastating disease that originates within the prostate gland, and subsequently disseminates throughout the body. A major goal of this project is to validate the concept that there is an ongoing relationship between the original tumor within the prostate gland, and the disseminated cancer cells in other parts of the body. Dr. Dicker and Dr. Knudsen are investigating whether radiation therapy of the primary tumor in advanced prostate cancer has a deleterious effect on the survival and growth of distant metastatic lesions in the bone. To test this they have successfully created a novel animal model of metastatic prostate cancer and have designed an apparatus that can deliver focal radiation therapy to the mouse prostate (a very small organ) only and not the rest of the animal. Currently, the team from Thomas Jefferson University is using these tools to definitively demonstrate whether or not local control of the primary tumor via radiation therapy will have a clinical benefit for patients with metastatic disease.