Dr. Alsina's basic research interests are in the area of multiple myeloma and how the bone marrow microenvironment influences the pathogenesis of the disease. Her main project in the laboratory at this time is to evaluate how this microenvironment influences gene expression profile in freshly isolated cells from patients with myeloma. These studies are part of a phase III clinical trial for patients with newly diagnosed myeloma, through which they get randomized to receive one of two induction treatments. Bone marrow samples are obtained before and after treatment. After myeloma cells are purified by CD138 sorting, they are adhered to fibronectin or kept in suspension and then collected for gene expression analysis. She and her colleagues plan to perform similar studies using other models of adhesion, including bone marrow stroma, and using laser capture microdissection in bone marrow biopsy specimens. This work should help elucidate the mechanisms through which the bone marrow microenvironment induces tumor growth and drug resistance.
Dr. Alsina's other main project is to test novel compounds that have potential to inhibit the interaction of myeloma cells and stromal cells, thereby overcoming cell adhesion'mediated drug resistance (CAM-DR), a form of de novo drug resistance. As part of the phase III trial already mentioned, she and her colleagues are evaluating the effects of zoledronic acid, a potent bisphosphonate, on CAM-DR and response to therapy. They and others have shown that bisphosphonates inhibit myeloma cell adhesion and myeloma cell homing to the bone marrow in in vivo models. Their hypothesis is that, by interfering with myeloma-stromal cell interactions, bisphosphonates sensitize cells to chemotherapy. In this trial, patients receive the bisphosphonate either with the chemotherapy or after chemotherapy to test this hypothesis.
Dr. Alsina and her clinical colleagues have developed a very active myeloma program with over 200 new patients per year. They have been conducting clinical research, testing the use of novel targeted therapies in phase I and II clinical trials. These trials have examined the use of thalidomide and its derivatives, proteasome inhibitors, farnesyl transferase inhibitors, insulin-like growth factor receptor antagonists, and other agents in the treatment of myeloma.