Heat Shock Protein 70 Inhibitor Shows Potent Antimyeloma Activity

An experimental drug has been shown to effectively complement and enhance the activity of chemotherapeutic agents used to treat multiple myeloma.

Multiple myeloma (MM) is the second most common hematologic malignancy and remains incurable, primarily due to the treatment-refractory/resistant nature of the disease. The experimental drug MAL3-101, developed at the University of Pittsburgh (PA, USA), is a member of a new class of non-ATP-site inhibitors of the heat shock protein (Hsp) 70 molecular chaperone.

Investigators at the State University of New York Downstate Medical Center (NY, USA) examined the effect of MAL3-101 on MM cells growing in culture and in vivo in a xenograft plasmacytoma model, as well as on primary tumor cells and bone marrow endothelial cells from myeloma patients.

They reported in the December 2011online edition of the Journal of Oncology that MAL3-101 exhibited antimyeloma effects on MM cell lines in vitro and in all the in vivo models studied. Administration of MAL3-101 together with the proteasome inhibitor bortezomib, significantly boosted its antimyeloma effects.

“The results of our study are very encouraging,” said senior author Dr. Olcay Batuman, professor of medicine and cell biology at the State University of New York Downstate Medical Center. “While this is not a cure and it will be some time before the compound is developed as a drug, we believe that MAL3-101, when used synergistically with existing therapies, could reduce overall drug concentrations and avoid treatment resistance.”

“It is possible to speculate that MAL3-101 may also modulate development of the multiple myeloma cancer stem cell,” said Dr. Batuman. “The relapse of multiple myeloma in patients in whom complete remission had been achieved is currently thought to indicate the presence of treatment-resistant multiple myeloma cancer stem cells. At Downstate, a group effort is now geared towards identifying and targeting these cancer stem cells in multiple myeloma. The antimyeloma effects of MAL3-101 could include inhibition of cancer stem cell development, since the Hsp-70 function is required in early plasma cell development. Our prediction is that antagonism of the Hsp-70 chaperone or chaperones by affecting nonredundant pathways could be effective in multiple myeloma treatment.”

Related Links:
University of Pittsburgh
State University of New York Downstate Medical Center