Current treatments for cancer patients include chemotherapy, radiation, hormonal therapy and immune-mediated therapies. However, despite favorable initial response, many patients develop recurrences or relapses. Resistance to cancer therapy has paved the way for novel therapeutic approaches. Dr. Benjamin Bonavida and his colleagues are working toward identifying the mechanisms causing cancer patients to develop resistance to treatment. The classification of such mechanisms will allow for the development of novel therapeutics to overcome such resistance.
Bonavida and colleagues have focused on areas of both cellular and molecular immunology as they relate to infection and cancer. During the last several years, the laboratory has focused on the molecular mechanism by which rituximab (chimeric anti-CD20 monoclonal antibody), approved by the U.S. Food and Drug Administration in 1999 for the treatment of non-Hodgkin's B lymphoma, mediates its effects when used alone or in combination with chemotherapy.
Bonavida's group has also been interested in investigating the molecular mechanism by which cancer patients develop resistance to immunotherapy. At present, immunotherapy is being considered as a novel therapeutic approach in the treatment of cancer patients who do not respond to conventional therapies. Several studies have examined the underlying mechanisms of immune-resistance and have identified several gene products involved. In particular, Dr. Bonavida and associates have identified the role of the transcription repressor YY1 in the regulation of immune-resistance.
Selected Cancer-Related Publications:
Baritaki S, Huerta-Yepez S, Sahakyan A, Karagiannides I, Bakirtzi K, Jazirehi A, Bonavida B. Mechanisms of nitric oxide-mediated inhibition of EMT in cancer: inhibition of the metastasis-inducer Snail and induction of the metastasis-suppressor RKIP. Cell Cycle. 2010 Dec 15;9(24):4931-40. Epub 2010 Dec 15.
Vega MI, Baritaki S, Huerta-Yepez S, Martinez-Paniagua MA, Bonavida B. A potential mechanism of rituximab-induced inhibition of tumor growth through its sensitization to tumor necrosis factor-related apoptosis-inducing ligand-expressing host cytotoxic cells. Leuk Lymphoma. 2011 Jan;52(1):108-21. Epub 2010 Dec 6.
Bonavida B, Baritaki S. Dual role of NO donors in the reversal of tumor cell resistance and EMT: Downregulation of the NF-kappaB/Snail/YY1/RKIP circuitry. Nitric Oxide. 2011 Jan 1;24(1):1-7. Epub 2010 Oct 8.
Baritaki S, Chapman A, Yeung K, Spandidos DA, Palladino M, Bonavida B. Inhibition of epithelial to mesenchymal transition in metastatic prostate cancer cells by the novel proteasome inhibitor, NPI-0052: pivotal roles of Snail repression and RKIP induction. Oncogene. 2009 Oct 8;28(40):3573-85. Epub 2009 Jul 27.
Baritaki S, Yeung K, Palladino M, Berenson J, Bonavida B. Pivotal roles of snail inhibition and RKIP induction by the proteasome inhibitor NPI-0052 in tumor cell chemoimmunosensitization. Cancer Res. 2009 Nov 1;69(21):8376-85. Epub 2009 Oct 20.