The Dana Farber/Harvard Cancer Center (DF/HCC) multiple myeloma (MM) SPORE renewal application consists of 6 Research Projects and 3 Cores, as well as the Career Development and Developmental Research Programs. During the previous funding period, we have capitalized on the complementary strengths of the research, clinical expertise, and facilities of the Harvard affiliated institutions including Dana- Farber Cancer Institute, Harvard Medical School, Harvard School of Public Health, as well as the Mayo Clinic. We have successfully translated multiple novel agents from the bench to the bedside and FDA approval for treatment of MM. Three projects in this renewal SPORE application have evolved from prior Developmental Projects, and two Career Development awardees are now Principal Investigator or Co- Investigators of new projects. One of the new projects focuses on genotypic and epidemiologic studies in multi-ethnic population, reflecting our emphasis on minority studies. We have established a collaborative effort, both in preclinical cellular and molecular studies and in joint clinical protocols. The group as a whole has a long-term commitment to translational MM research, with the necessary administrative, basic science, and clinical infrastructure. At these well established centers, more than 750 new patients with MM are evaluated annually, as well as 10,000 outpatient visits for established patients with plasma cell dyscrasias. The spectrum of diseases evaluated spans from monoclonal gammopathy of unclear significance to plasma cell leukemia. Each center has appropriate scientific and institutional review boards, as well as protocol audit and quality control centers, to conduct cutting edge translational research. There are presently more than 50 active protocols evaluating therapies including novel drugs, immune treatments, improved stem cell transplantation, and supportive therapies in MM. This large combined patient base assures rapid accrual and evaluation of the therapeutic efficacy of novel agents identified in this program. Success of both the preclinical and clinical components of this Program will be dependent upon synergy and communication between these centers. To assure this end, we have set up an Internet site that allows access to all the Principal Investigators to the preclinical data generated in joint research efforts. Similarly, data from the joint clinical protocol trials will also be deposited in this secure web site to allow a seamless and uniform conduct of clinical studies at these sites. Currently there is systematic quality-controlled exchange of bone marrow and blood samples for correlative basic laboratory studies. The overall theme of the DF/HCC myeloma SPORE is to identify and evaluate novel targeted therapies. The translational nature of the SPORE is highlighted by the fact that most of our projects have emanated from clinical studies from the outset. Specific Projects are (1) Overcoming Proteasome-lnhibitor Resistance in Multiple Myeloma;(2) Targeting Telomere Expansion Mechanisms For Myeloma Therapy;(3) Targeting the Wnt Pathway for Treatment of Multiple Myeloma;(4) Targeting Activation of NF-?B Pathways in Multiple Myeloma;(5) Molecular Markers of Plasma Cell Neoplasm Evolution;and (6) Identifying High Risk Genotypes for Multiple Myeloma: A Collaborative Multi-Ethnic Case-Controlled Study. Core resources include Administrative Communication and Planning Core (1), Tissue Core (2), and Biostatistics and Bioinformatics Core (3). This Program therefore represents the integrated efforts of institutions with a unique and long track record of basic and clinical research expertise in MM, now joining together to more rapidly move rational novel targeted therapies from the laboratory to clinical protocols to improve patient outcome in MM.

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Specialized Center (P50)
Project #
5P50CA100707-10
Application #
8321878
Study Section
Special Emphasis Panel (ZCA1-GRB-I (M1))
Program Officer
Nothwehr, Steven F
Project Start
2003-09-16
Project End
2013-08-31
Budget Start
2012-09-01
Budget End
2013-08-31
Support Year
10
Fiscal Year
2012
Total Cost
$2,300,000
Indirect Cost
$652,144
Name
Dana-Farber Cancer Institute
Department
Type
DUNS #
076580745
City
Boston
State
MA
Country
United States
Zip Code
02215
Das, D Sharma; Ray, A; Das, A et al. (2016) A novel hypoxia-selective epigenetic agent RRx-001 triggers apoptosis and overcomes drug resistance in multiple myeloma cells. Leukemia 30:2187-2197
Tagde, Ashujit; Rajabi, Hasan; Stroopinsky, Dina et al. (2016) MUC1-C induces DNA methyltransferase 1 and represses tumor suppressor genes in acute myeloid leukemia. Oncotarget 7:38974-38987
Lin, Jianhong; Zhang, Weihong; Zhao, Jian-Jun et al. (2016) A clinically relevant in vivo zebrafish model of human multiple myeloma to study preclinical therapeutic efficacy. Blood 128:249-52
Hunter, Zachary R; Xu, Lian; Yang, Guang et al. (2016) Transcriptome sequencing reveals a profile that corresponds to genomic variants in Waldenström macroglobulinemia. Blood 128:827-38
Ray, Arghya; Ravillah, Durgadevi; Das, Deepika S et al. (2016) A novel alkylating agent Melflufen induces irreversible DNA damage and cytotoxicity in multiple myeloma cells. Br J Haematol 174:397-409
Mullikin, Trey C; Rajkumar, S Vincent; Dispenzieri, Angela et al. (2016) Clinical characteristics and outcomes in biclonal gammopathies. Am J Hematol 91:473-5
An, Gang; Acharya, Chirag; Feng, Xiaoyan et al. (2016) Osteoclasts promote immune suppressive microenvironment in multiple myeloma: therapeutic implication. Blood 128:1590-603
Tagde, Ashujit; Rajabi, Hasan; Bouillez, Audrey et al. (2016) MUC1-C drives MYC in multiple myeloma. Blood 127:2587-97
Jiang, H; Acharya, C; An, G et al. (2016) SAR650984 directly induces multiple myeloma cell death via lysosomal-associated and apoptotic pathways, which is further enhanced by pomalidomide. Leukemia 30:399-408
Gullà, Annamaria; Di Martino, Maria Teresa; Gallo Cantafio, Maria Eugenia et al. (2016) A 13 mer LNA-i-miR-221 Inhibitor Restores Drug Sensitivity in Melphalan-Refractory Multiple Myeloma Cells. Clin Cancer Res 22:1222-33

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