Grant: Fellowship - Priority Announcement: Melanoma (SHOPP)

The major challenge in cancer therapy is to stop its progression to more advanced stages (metastasis) where the disease becomes resistant to most forms of therapeutic interventions. Understanding the mechanisms leading to metastasis is only beginning to emerge and is key to develop specific therapeutic interventions. Another complicating factor in cancer therapy is the diversity of cancer cells within a tumor, also called heterogeneity, that makes it difficult to optimize therapeutic regimen in individual patients, also referred to as personalized medicine. Recent advances have uncovered novel ways to diagnose, follow and potentially treat cancer using a unique therapeutic target known as circulating tumors cells (CTCs). These cells are shed from the primary tumor or its metastatic sites and recapitulate many of the features of tumor heterogeneity. Importantly, CTCs number follow closely the progression or regression of the disease making them ideal candidates for developing personalized therapeutic regimens. However, CTCs circulate in very low number making it difficult to study them using standard blood test procedures. Recently, we have developed a novel approach to isolate CTCs in large numbers from a series of breast cancer patients by a procedure called aphaeresis. Furthermore, we have banked these live cells at ultra-low temperature and we are studying them in detail. We plan to apply the same procedure to melanoma patients where we intend to identify unique CTC markers that can aid us in predicting the course of the disease. Also, we will test the CTCs response to a variety of chemotherapeutic agents in view of developing personalized therapeutic regimen. Finally, the proposed approach could be applied to a variety of cancer types in the near future.