Multiple Myeloma
The Washington University Center for Multiple Myeloma Nanotherapy (CMMN) is a federally-funded program that was developed to improve the treatment outcomes of people with multiple myeloma. Innovative approaches to myeloma treatment are urgently needed. As part of the CMMN, the focus of our lab and close collaborators is on optimizing the delivery of novel prodrugs via nanotechnology to improve safety and efficacy in multiple myeloma (MM) treatment.
Outside Institutional Collaborators:
Dr. Michael Tomasson, MD, Department of Internal Medicine, Carver College of Medicine, the University of Iowa
Dr. Steven Fletcher, PhD, Pharmaceutical Sciences Department, University of Maryland School of Pharmacy
Dr. Edward V. Prochownik, MD PhD, Children’s Hospital of Pittsburgh, University of Pittsburgh School of Medicine
In the News: Nanotherapy effective in mice with multiple myeloma:
Researchers at Washington University School of Medicine in St. Louis have developed a nanotherapy that is effective in treating mice with multiple myeloma, a cancer of bone marrow immune cells.
Breast Cancer Metastases in Bone
Bone metastases occur in approximately 70% of metastatic breast cancer patients, often leading to skeletal injuries. Current treatments are mainly palliative and underscore the unmet clinical need for improved therapies. Breast cancer cells within the bone selectively up-regulate the expression of integrin αvβ3 due to TGF-β in the bone microenvironment. Using a micelle-based nanoparticle (10-20 nm) therapy that binds activated integrin αvβ3, a lipase labile Sn2 docetaxel prodrug reduced bone tumor burden and ameliorated bone destruction without the hepatotoxicity caused by equimolar doses of free drug. Ultimately the aim is to use integrin αvβ3-targeted drug delivery as a bone-specific therapeutic strategy to address the unmet clinical need for effective treatments against breast cancer bone metastases.
Collaborators:
Katherine N. Weilbaecher, MD
Figure: Left. Schematic of αvβ3-targeted micelle particle “contact-facilitated drug delivery.” Upon hemifusion, phospholipid-conjugated docetaxel-prodrug (DTX-PD) transfers to the target cell’s plasma membrane, where bioactive DTX is enzymatically liberated by phospholipases and released directly into the cytoplasm. Right. Integrin αvβ3-targeted nanotherapy attenuates breast cancer bone metastases.
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