The Dana Farber/Harvard Cancer Center (DF/HCC) multiple myeloma (MM) SPORE renewal application consists of 4 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, Massachusetts General Hospital, Harvard Medical School, Harvard School of Public Health. We have successfully translated multiple novel agents from the bench to the bedside and FDA approval for treatment of MM. Two projects in this renewal SPORE application have evolved from prior Developmental Projects, and five investigators who are now Co-PI's have previously received developmental research funding from SPORE. One of the new projects focuses on epigenetic studies in myeloma. We have established a collaborative effort, both in preclinical cellular and molecular studies as well as joint clinical protocols. The group a 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. Our center has appropriate scientific and institutional review boards, as well as protocol audit and quality contrl centers, to conduct cutting-edge translational research. There are presently more than 26 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 investigators. 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. 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) Targeting deubiquitylating enzymes in multiple myeloma;(2) Targeting genomic instability in multiple myeloma;(3) Targeting the MUC1-C Oncoprotein in Multiple Myeloma;(4) Targeting the Multiple Myeloma Epigenome;(A) Administration Communication and Planning Core;(B) Tissue Core, and (C) Biostatistics and Bioinformatics Core. This Program therefore help move rational novel targeted therapies from the laboratory to clinical protocols to improve patient outcome in MM.

Public Health Relevance

This application represents the integrated efforts of DF/HCC institutions with a unique and long track record of basic and clinical research expertise in Multiple Myeloma (MM), joined together to 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 #
5P50CA100707-12
Application #
8737174
Study Section
Special Emphasis Panel (ZCA1-RPRB-0 (O1))
Program Officer
Nothwehr, Steven F
Project Start
2003-09-01
Project End
2018-08-31
Budget Start
2014-09-01
Budget End
2015-08-31
Support Year
12
Fiscal Year
2014
Total Cost
$2,162,001
Indirect Cost
$841,970
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

Showing the most recent 10 out of 351 publications