Our long-term goal is to develop novel, mechanism-based combination approaches (involving targeted radiation and cytotoxic drugs) for cancer therapy. Currently the lab is pursuing following lines of study:
- Incorporation of skeleton-targeted radiotherapy (STR) into therapeutic regimens for multiple myeloma. The overall goal of this project is to understand how best to target constitutive and radiation-induced NF-kB activation to inhibit downstream IL6 synthesis, which would selectively radiosensitize myeloma cells and prevent the development of myeloma-cell drug resistance in the bone marrow microenvironment. Strategies to circumvent oxidative stress-induced emergence of therapy-resistance in myeloma cells are being studied. Also, based on our knowledge of the major signaling pathways that drive the proliferation of myeloma cells, we are evaluating a panel of molecularly targeted drugs for their ability to selectively enhance the therapeutic index of radiation-based treatment in myeloma. The project has a direct extension to the use of STR-based combination approaches to other malignancies such as breast and prostate cancer.
- Incorporation of radiovirotherapy into therapeutic regimens for multiple myeloma. We have generated and characterized a novel oncolytic vesicular stomatitis virus (VSV) that expresses human thyroidal NIS, and demonstrated 1) feasibility of performing viral biodistribution studies by micro-SPECT/CT imaging, and 2) attained therapeutic responses by combining VSV-NIS with I-131 in mice bearing systemic myeloma. We are currently performing studies to assess the therapeutic benefit of combining radiovirotherapy with 153-Sm-EDTMP and radiosensitizing drugs in the treatment of advanced systemic myeloma and B-cell lymphoma.
- Incorporation of chemotherapy into therapeutic regimens for lymphoma. Radioimmunotherapy is an established and effective treatment modality in lymphoma. As part of UI-Mayo Lymphoma SPORE, we are studying the role of VLA-4 (α4β1 integrin) adhesion receptor in cell adhesion-mediated drug resistance (CAM-DR) and CAM radiation resistance (CAM-RR).