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.
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.
|Xu, Yan; Deng, Shuhui; Mao, Xuehan et al. (2018) Tolerance, Kinetics, and Depth of Response for Subcutaneous Versus Intravenous Administration of Bortezomib Combination in Chinese Patients With Newly Diagnosed Multiple Myeloma. Clin Lymphoma Myeloma Leuk 18:422-430|
|Michallet, M; Chapuis-Cellier, C; Dejoie, T et al. (2018) Heavy+light chain monitoring correlates with clinical outcome in multiple myeloma patients. Leukemia 32:376-382|
|Ray, A; Das, D S; Song, Y et al. (2018) Combination of a novel HDAC6 inhibitor ACY-241 and anti-PD-L1 antibody enhances anti-tumor immunity and cytotoxicity in multiple myeloma. Leukemia 32:843-846|
|Guang, Matthew Ho Zhi; McCann, Amanda; Bianchi, Giada et al. (2018) Overcoming multiple myeloma drug resistance in the era of cancer 'omics'. Leuk Lymphoma 59:542-561|
|Perrot, Aurore; Lauwers-Cances, Valerie; Corre, Jill et al. (2018) Minimal residual disease negativity using deep sequencing is a major prognostic factor in multiple myeloma. Blood 132:2456-2464|
|Tai, Yu-Tzu; Lin, Liang; Xing, Lijie et al. (2018) APRIL signaling via TACI mediates immunosuppression by T regulatory cells in multiple myeloma: therapeutic implications. Leukemia :|
|Gonsalves, Wilson I; Buadi, Francis K; Ailawadhi, Sikander et al. (2018) Utilization of hematopoietic stem cell transplantation for the treatment of multiple myeloma: a Mayo Stratification of Myeloma and Risk-Adapted Therapy (mSMART) consensus statement. Bone Marrow Transplant :|
|Bae, J; Hideshima, T; Zhang, G L et al. (2018) Identification and characterization of HLA-A24-specific XBP1, CD138 (Syndecan-1) and CS1 (SLAMF7) peptides inducing antigens-specific memory cytotoxic T lymphocytes targeting multiple myeloma. Leukemia 32:752-764|
|Ye, Shuai; Lawlor, Matthew A; Rivera-Reyes, Adrian et al. (2018) YAP1-Mediated Suppression of USP31 Enhances NF?B Activity to Promote Sarcomagenesis. Cancer Res 78:2705-2720|
|Hunter, Zachary R; Xu, Lian; Tsakmaklis, Nickolas et al. (2018) Insights into the genomic landscape of MYD88 wild-type Waldenström macroglobulinemia. Blood Adv 2:2937-2946|
Showing the most recent 10 out of 407 publications