• Researcher Profile

    Kenneth C. Anderson, MD

     
    Program Director, Jerome Lipper Multiple Myeloma Center and LeBow Institute for Myeloma Therapeutics
    Institute Physician


    Kraft Family Professor of Medicine, Harvard Medical School

    Center/Program

    Hematologic Oncology

    Office phone: 617-632-2144
    Fax: 617-632-2140
    Email: kenneth_anderson@dfci.harvard.edu

    Preferred contact method: appointment phone

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    Research Department

    Medical Oncology/Hematologic Neoplasia

    Interest

    Multiple myeloma, Stem cell/bone marrow transplant

    Area of Research

    Novel Biologically Based Therapies for Multiple Myeloma

    Dana-Farber Cancer Institute
    450 Brookline Avenue
    Mayer 557
    Boston, MA 02215

    Biography

    Dr. Anderson graduated from Johns Hopkins Medical School, trained in internal medicine at Johns Hopkins Hospital, and completed hematology, medical oncology, and tumor immunology training at Dana-Farber Cancer Institute.

    He serves as chief of the Division of Hematologic Neoplasia, director of the Jerome Lipper Multiple Myeloma Center, and vice chair of the Joint Program in Transfusion Medicine at Dana-Farber.

    Recent Awards

    • Robert A. Kyle Lifetime Achievement Award, 2005

    Research

    Novel Biologically Based Therapies for Multiple Myeloma

    Our recent advances in genomics and proteomics in multiple myeloma (MM) have increased our understanding of disease pathogenesis, helped to identify novel therapeutic targets, and provided the scientific rationale for combining targeted therapies to increase tumor-cell cytotoxicity and abrogate drug resistance. Specifically, gene microarray profiling has shown major differences between normal plasma cells and cells from monoclonal gammopathy of unclear significance (MGUS) and MM cells, with further modulations within MM cells and in cells progressing to plasma cell leukemia. Therefore, we have profiled individual patients newly diagnosed with MM in order to tailor targeted therapy for them; it is likely that cocktails of therapeutics will be needed to overcome resistance.

    Recognition of the role of the bone marrow (BM) milieu in conferring growth, survival, and drug resistance in MM cells - in both the laboratory and in animal models - has enabled us to establish a new treatment paradigm targeting the tumor cell and its microenvironment. Our studies in a SCID-human mouse model of MM have demonstrated modulations associated with binding of MM cells to the BM microenvironment: upregulation of growth-, survival-, and drug-resistance genes in MM cells; increased adhesion molecule expression on MM cells and bone marrow stromal cells (BMSCs); and increased cytokine transcription and secretion in BMSCs. Thalidomide, the proteasome inhibitor bortezomib, and the novel immunomodulatory drug lenalidamide maintain their cytotoxicity against MM cells even in the BM milieu. They do so by: (1) directly inducing apoptosis of drug-resistant MM cells; (2) decreasing the adhesion of MM cells to BMSCs and extracellular matrix proteins; (3) downregulating the transcription and secretion of cytokines in the BM milieu that mediate tumor cell growth, survival, and migration; (4) inhibiting angiogenesis; and (5) stimulating host antiMM immunity. Each of these drugs has been shown to have antitumor activity in relapsed and refractory MM, whether alone or combined with dexamethasone. Clinical trials have also evaluated their utility earlier in the disease course.

    Finally, our correlative gene profiling, proteomic, and signaling studies in tumor cell samples from patients treated with novel agents have identified the mechanisms of sensitivity and resistance, provided the rationale for selection of patients most likely to respond, helped to design combination therapies to enhance sensitivity and overcome resistance in MM cells, and suggested ways to develop more potent, selective, and less toxic targeted therapeutics.

    Trainees

    • Catley, Laurie, MD
    • Ishituska, Kenji, MD, PhD
    • Kiziltepe, Tanyel, PhD
    • Yasui, Hiroshi, MD, PhD
    • Raje, Noopur, MD
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