Our myeloma research group, which has developed number of new targets and novel therapies (DFCI), will partner with the world leaders in cooperative clinical and transplantation trials in MM (IFM) to pursue collaborative translational investigation. We will couple combination novel therapies with high dose therapy and transplantation and then delineate genomic and molecular correlates of clinical and biological outcomes. Project 1 will focus on defining the durability of responses to novel combination therapy on the one hand, and the additional value of high dose therapy on the other, by enrolling 1000 newly diagnosed patients between IFM and DFCI. This trial will provide 1000 samples from newly diagnosed and uniformly treated patients to comprehensively characterize the MM genome and epigenome, to define molecular events driving development and progression of MM (Project 2), as well as to identify novel therapeutic targets (Project 3), biomarkers, and preventative strategies (Project 4). In these collaborative studies the Sanger Institute in UK, with whole genome sequencing capabilities, along with research teams from DFCI and IFM, will perform molecular genetic analysis of patient samples and delineate patient subgroups most likely to respond and achieve prolonged survival (Projects 2 and 4). The clinically relevant novel targets identified using these high throughput genomic technologies will be validated and novel targeted therapies developed in Project 3. Project 4 will further analyze evolution of genomic changes at relapse and their clinical significance, as well as devise strategies to prevent genomic instability. These 4 projects will be supported by Administrative and Communication Core (A), Clinical and Tissue Core (B);Genomics Core (C);Genomic Sequencing Core (0), and Biostatistical and Bioinformatics Core (E). This unique collaborative effort will define a new treatment paradigm for this presently incurable disease.
This program will help define the role of high dose therapy and transplantation in the era of novel therapies Moreover, the oncogenomic studies will both identify genomic correlates of disease behavior and identify targets for novel therapeutics to develop next generation of therapies in myeloma.
|GullÃ , 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|
|Prabhala, R H; Fulciniti, M; Pelluru, D et al. (2016) Targeting IL-17A in multiple myeloma: a potential novel therapeutic approach in myeloma. Leukemia 30:379-89|
|Magrangeas, Florence; Kuiper, Rowan; Avet-Loiseau, HervÃ© et al. (2016) A Genome-Wide Association Study Identifies a Novel Locus for Bortezomib-Induced Peripheral Neuropathy in European Patients with Multiple Myeloma. Clin Cancer Res 22:4350-5|
|Ohguchi, Hiroto; Hideshima, Teru; Bhasin, Manoj K et al. (2016) The KDM3A-KLF2-IRF4 axis maintains myeloma cell survival. Nat Commun 7:10258|
|Dimopoulos, Meletios A; Orlowski, Robert Z; Facon, Thierry et al. (2015) Retrospective matched-pairs analysis of bortezomib plus dexamethasone versus bortezomib monotherapy in relapsed multiple myeloma. Haematologica 100:100-6|
|Bianchi, Giada; Munshi, Nikhil C (2015) Pathogenesis beyond the cancer clone(s) in multiple myeloma. Blood 125:3049-58|
|Jagannathan, S; Vad, N; Vallabhapurapu, S et al. (2015) MiR-29b replacement inhibits proteasomes and disrupts aggresome+autophagosome formation to enhance the antimyeloma benefit of bortezomib. Leukemia 29:727-38|
|Hu, Y; Song, W; Cirstea, D et al. (2015) CSNK1Î±1 mediates malignant plasma cell survival. Leukemia 29:474-82|
|Hebraud, Benjamin; Magrangeas, Florence; Cleynen, Alice et al. (2015) Role of additional chromosomal changes in the prognostic value of t(4;14) and del(17p) in multiple myeloma: the IFM experience. Blood 125:2095-100|
|Mitsiades, Constantine S (2015) Therapeutic landscape of carfilzomib and other modulators of the ubiquitin-proteasome pathway. J Clin Oncol 33:782-5|
Showing the most recent 10 out of 161 publications