The Washington University Center for Multiple Myeloma Nanotherapy (WU CMMN) will address overarching questions in bone malignancies, with a focus on multiple myeloma (MM). MM is a hematopoietic malignancy caused by terminally differentiated malignant plasma B-cells. Myeloma cells simultaneously activate the bone resorbing osteoclast cells in the bone marrow and inhibit bone forming osteoblast cells, culminating in a vicious cycle of tumor growth and bone destruction. A grim result of this interplay is that 80% of MM patients present bone lesions including pathologic fracture at diagnosis. Despite tremendous improvements in MM patient management, more than 24,000 new cases and 11,000 deaths occurred in 2014 alone. Additionally, the side effects of chemotherapeutics can result in increased risk of systemic toxicity and hospitalization costs. An impaired bone marrow reserve imposes additional constraints on how best to deliver therapy without producing worsening cytopenias and further increasing the risk for complications. About 10% of patients have primary refractory disease and fail to respond to induction treatments. Thus, although newer molecular therapeutics may extend patient survival, nearly all patients will eventually relapse and die from MM. The long-term goal of our CMMN is to provide curative outcomes by developing novel nanotherapeutics that utilizes unique drug delivery mechanism and multidimensional treatment paradigms to accomplish our goal. Anchored by 3 projects and two cores, we aim to (1) develop integrated curative approach for the treatment of MM with minimal off target toxicity; (2) identify nanotherapeutics for clinical translation; (3) provide a platform to educate, train, and mentor young investigators and students on techniques and methods of cancer nanomedicine; (4) create environment for productive outreach programs that brings researchers and patients together through workshops and seminars; and (5) collaborate with other CCNEs and investigators in the region to share information and resources with a goal to accelerating clinical translation of nanomedicine to human patients. Beyond MM, successful completion of the proposed research will advance the treatment of hematological diseases in general and usher new therapies for tackling the challenges in treating bone marrow metastasis.

Public Health Relevance

Multiple myeloma (MM) is a cancer of the bone marrow and although most patients respond well to initial chemotherapy, nearly all patients will eventually relapse and die from MM. The primary objective of this program is to find a cure for MM or minimize relapse through the development of nanoptherapeutics and monitoring treatment response by noninvasive imaging methods.

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Specialized Center--Cooperative Agreements (U54)
Project #
1U54CA199092-01
Application #
8962044
Study Section
Special Emphasis Panel (ZCA1-TCRB-Q (M1))
Program Officer
Grodzinski, Piotr
Project Start
2015-09-01
Project End
2020-07-31
Budget Start
2015-09-01
Budget End
2016-07-31
Support Year
1
Fiscal Year
2015
Total Cost
$2,229,839
Indirect Cost
$706,364
Name
Washington University
Department
Radiation-Diagnostic/Oncology
Type
Schools of Medicine
DUNS #
068552207
City
Saint Louis
State
MO
Country
United States
Zip Code
63130
Ye, Dezhuang; Zhang, Xiaohui; Yue, Yimei et al. (2018) Focused ultrasound combined with microbubble-mediated intranasal delivery of gold nanoclusters to the brain. J Control Release 286:145-153
Miller, Jessica; Wang, Steven T; Orukari, Inema et al. (2018) Perfusion-based fluorescence imaging method delineates diverse organs and identifies multifocal tumors using generic near-infrared molecular probes. J Biophotonics 11:e201700232
Ye, Dezhuang; Sultan, Deborah; Zhang, Xiaohui et al. (2018) Focused ultrasound-enabled delivery of radiolabeled nanoclusters to the pons. J Control Release 283:143-150
Karakocak, Bedia Begum; Liang, Jue; Biswas, Pratim et al. (2018) Hyaluronate coating enhances the delivery and biocompatibility of gold nanoparticles. Carbohydr Polym 186:243-251
de la Puente, Pilar; Luderer, Micah J; Federico, Cinzia et al. (2018) Enhancing proteasome-inhibitory activity and specificity of bortezomib by CD38 targeted nanoparticles in multiple myeloma. J Control Release 270:158-176
White, Brian S; Lanc, Irena; O'Neal, Julie et al. (2018) A multiple myeloma-specific capture sequencing platform discovers novel translocations and frequent, risk-associated point mutations in IGLL5. Blood Cancer J 8:35
Cui, Grace; Akers, Walter J; Scott, Michael J et al. (2018) Diagnosis of LVAD Thrombus using a High-Avidity Fibrin-Specific 99mTc Probe. Theranostics 8:1168-1179
Hathi, Deep K; DeLassus, Elizabeth N; Achilefu, Samuel et al. (2018) Imaging Melphalan Therapy Response in Preclinical Extramedullary Multiple Myeloma with 18F-FDOPA and 18F-FDG PET. J Nucl Med 59:1551-1557
Ghai, Anchal; Maji, Dolonchampa; Cho, Nicholas et al. (2018) Preclinical Development of CD38-Targeted [89Zr]Zr-DFO-Daratumumab for Imaging Multiple Myeloma. J Nucl Med 59:216-222
Ghobadi, Armin; Rettig, Michael P; Holt, Matthew S et al. (2018) Ixazomib, an oral proteasome inhibitor, induces rapid mobilization of hematopoietic progenitor cells in mice. Blood 131:2594-2596

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