Inhibition of Metastases by Disrupting Platelet-Cancer Cell Interactions Using ex Vivo Modified Platelets
Abstract
Metastasis is the leading cause of death in cancer. According to the American Cancer Society, the incidence of invasive breast cancer represents 226,870 women and 2190 men in the US in 2012. Alarmingly, the Susan G. Komen foundation reports that a woman died from breast cancer every 13 minutes in the US in 2012. A cure for cancer can only emerge if we are able to impair or inhibit metastases. Metastases occur by the traveling of cancer cells from the primary site of tumor to distant organs. Both the bloodstream and the lymphatic system are like highways for these cells to travel before they can colonize a new site and multiply, leading to metastases. The metastatic cascade is extremely complex and requires interactions of circulating tumor cells (i.e., cells that have escaped from the primary tumor site) with multiple cells in the bloodstream: platelets, leucocytes (white blood cells) and endothelial cells (which line the blood vessels). The bloodstream is not a natural environment for cancer cells, and platelets provide assistance in many ways for cancer cells to survive: they release favorable growth factors to cancer cells, protect them from being identified and destroyed by the immune system, and help them to get attached to the endothelial cell lining in the vasculature, leading to downstream tumors. Circulating tumor cells are detected in 90% of non-metastatic breast cancer patients, and there is no treatment to directly prevent circulating tumor cells from disseminating to induce metastases in distant organs. The extent and speed of this metastatic spread is a significant determinant of patient survival. It is extremely urgent to develop targeted therapies meant to decelerate or stop this process. Our goal is to use modified platelets that are inert in nature to compete with platelets in the bloodstream and cut off their vital assistance to circulating tumor cells. Our preliminary data indicate that these modified platelets significantly interfere with platelet functions, and we envision that, if successful, these modified platelets could be rationally transfused to patients and could have a significant impact on their survival by delaying or impairing metastasis. We expect this cell-based drug-free therapy to be safe or to induce few side effects that can be easily reversed if necessary. In addition to interfering with the interplay between cancer cells and platelets, our proposed therapy could make cancer cells more detectable by the immune system and help the body s inherent defenses to fight the cancer. This approach could be particularly helpful in patients who have been identified to have aggressive advanced stage breast cancer but who are yet to have detectable spread to other parts of the body. Current screening methods have played a fundamental role in early diagnosis of breast cancer and currently according to SEER (Surveillance, Epidemiology, and End Results) cancer statistics, around 93% of woman diagnosed with breast cancer do not have metastases. This number confirms the broad applicability of this therapy in women at risk for future metastases. These patients can get superior control of their disease by first getting surgery of their breast cancer and then controlling the numerous cancer cells that have escaped into the blood with the help of our novel approach. Our in vivo studies will help us to validate our concept and will be a vital step towards developing this new therapeutic to attain our objective of enhancing patient survival and controlling metastasis in breast cancer.
Document Details
- Document Type
- DoD Grant Award
- Publication Date
- Apr 04, 2016
- Source ID
- W81XWH1510305
Entities
People
- Anne-Laure Papa
Organizations
- Harvard University
- United States Army