Multiple myeloma (MM) is a devastating hematologic malignancy that affects over 20,000 new patients every year in the USA. It typically responds well to treatment with DNA alkylators, glucocorticoids, proteasome inhibitors, and the IMiD class of Immunomodulator (thalidomide, lenalidomide and pomalidomide). Unfortunately, over time the disease becomes resistant to these drugs and patients relapse and die. We have identified 4 key areas of research that promise to translate into rapid clinical gains for the treatment of patients. 1) Develop dramatically new strategies to treat MM using next-generation approaches such as oncolytic virotherapy; 2) Given the success of IMiDs, study novel classes of immunomodulators with anti-MM activity, starting with SMAC mimetic compounds; 3) Determine the clinical significance of the most frequent mutation in MM, structural rearrangements of the MYC locus, and the effects of targeting MYC in patients with MM; 4) Explore clonal evolution in MM, including its contribution to drug resistance. To tackle these issues we have assembled a dedicated team of basic science and clinical investigators from all three Mayo Clinic sites, representing the largest MM program in the world. The projects are augmented by the strong collaborations of the project co-leaders, and through the three shared resource cores: Biospecimens Core, Biostatistics and Bioinformatics Core, and Administrative Core. The cores provide economy of effort and cost and support each of the projects. Finally to further enhance MM research and specifically the Aims of the 4 projects, this SPORE application supports novel translational studies through a Developmental Research Program (e.g., individual peptide monitoring by mass spectrometry to follow minimal residual disease), and through a mentored Career Development Program (e.g., developing novel immune therapies for MM) for young faculty. The historical and institutional commitment to MM research at Mayo Clinic is unequalled, and together with the leading role nationally and internationally in MM research of members of this SPORE we will be able to quickly translate our discoveries into new treatment strategies for patients with MM aimed not just at control, but ultimately to make cure become a reality.

Public Health Relevance

Most patients with multiple myeloma continue to die of the disease. This SPORE will develop new treatment approaches using oncolytic virotherapy and novel drugs that activate the immune system. In addition the SPORE will determine the clinical significance of mutations of the MYC locus, and recurrent point mutations in patients with multiple myeloma.

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Specialized Center (P50)
Project #
1P50CA186781-01A1
Application #
8930229
Study Section
Special Emphasis Panel (ZCA1)
Program Officer
Ujhazy, Peter
Project Start
2015-09-01
Project End
2020-08-31
Budget Start
2015-09-01
Budget End
2016-08-31
Support Year
1
Fiscal Year
2015
Total Cost
Indirect Cost
Name
Mayo Clinic, Arizona
Department
Type
DUNS #
153665211
City
Scottsdale
State
AZ
Country
United States
Zip Code
85259
Wang, Xin; Mazurkiewicz, Magdalena; Hillert, Ellin-Kristina et al. (2016) The proteasome deubiquitinase inhibitor VLX1570 shows selectivity for ubiquitin-specific protease-14 and induces apoptosis of multiple myeloma cells. Sci Rep 6:26979
Rajkumar, S Vincent (2016) Myeloma today: Disease definitions and treatment advances. Am J Hematol 91:90-100
Rajan, Archana M; Buadi, Francis K; Rajkumar, Vincent (2016) Effective use of panobinostat in combination with other active agents in myeloma in a novel five-drug combination: Case report and interesting observations. Am J Hematol 91:E5-6
Rajkumar, S Vincent; Kumar, Shaji (2016) Multiple Myeloma: Diagnosis and Treatment. Mayo Clin Proc 91:101-19
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Siontis, B; Kumar, S; Dispenzieri, A et al. (2015) Positron emission tomography-computed tomography in the diagnostic evaluation of smoldering multiple myeloma: identification of patients needing therapy. Blood Cancer J 5:e364

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