A new study from SUNY Downstate Medical Center in Brooklyn, New York, shows that MAL3-101, a recently developed inhibitor of the heat shock protein 70 (Hsp70), appears to have potent anti-tumor effects on multiple myeloma, a bone marrow cancer. Despite aggressive modes of treatments, myeloma ultimately remains incurable. The disease has a high incidence in the communities served by SUNY Downstate.
The findings, published in a recent issue of Journal of Oncology, are the result of a collaborative effort among researchers working in the laboratory of Olcay Batuman, MD, at Downstate; scientists at the University of Pittsburgh, where the small molecule inhibitor MAL3-101 was developed; scientists at the University of California at San Francisco; and other collaborators at SUNY Downstate.
Multiple myeloma is characterized by an accumulation and expansion of neoplastic plasma cells in the bone marrow. Normally, these white blood cells manufacture the antibodies needed to fight infection. When plasma cells become cancerous, however, they invade the bone marrow and the skeleton, and the immune system is severely compromised. Skeletal fragility, fatigue, weight loss, kidney failure, and repeated infections are common key manifestations and causes of morbidity and mortality from multiple myeloma. The risk for developing this disease increases with age.
"Currently multiple myeloma remains an incurable disease, despite the use of stem cell transplants, high-dose chemotherapy, and radiation," explains Dr. Batuman, professor of medicine and cell biology at Downstate and head of the research team that conducted the study. "New treatment modalities are urgently needed," she says.
The study aimed to explore the cytotoxic effects of MAL3-101 on multiple myeloma tumor growth. The researchers found that MAL3-101 exhibited anti-myeloma effects both in vitro and in vivo on tumor cell lines, as well as on primary tumor and endothelial cells from patients. When used in animal studies with the proteasome inhibitor bortezomib, MAL3-101 significantly boosted its anti-myeloma effects. Dr. Batuman's team found that by targeting Hsp70 activity, the dosage of synergic agents such as bortezomib could be reduced without compromising their effectiveness. The ability to reduce dosage makes it possible to continue the use of drugs that are toxic at higher concentrations. The addition of new synergistic agents also enriches the treatment arsenal by reducing drug resistance.
"The results of our study are very encouraging," says Dr. Batuman. "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."
Dr. Batuman adds, "It is possible to speculate that MAL3-101 may also modulate development of the multiple myeloma cancer stem cell. 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 anti-myeloma 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 non-redundant pathways could be effective in multiple myeloma treatment."
SUNY Downstate Medical Center, founded in 1860, was the first medical school in the United States to bring teaching out of the lecture hall and to the patient's bedside. A center of innovation and excellence in research and clinical service delivery, SUNY Downstate Medical Center comprises a College of Medicine, Colleges of Nursing and Health Related Professions, a School of Graduate Studies, a School of Public Health, University Hospital of Brooklyn, and an Advanced Biotechnology Park and Biotechnology Incubator.
SUNY Downstate ranks ninth nationally in the number of alumni who are on the faculty of American medical schools. More physicians practicing in New York City have graduated from SUNY Downstate than from any other medical school.
Ron Najman | EurekAlert!
The genes are not to blame
20.07.2018 | Technische Universität München
Targeting headaches and tumors with nano-submarines
20.07.2018 | Universitätsmedizin der Johannes Gutenberg-Universität Mainz
A new manufacturing technique uses a process similar to newspaper printing to form smoother and more flexible metals for making ultrafast electronic devices.
The low-cost process, developed by Purdue University researchers, combines tools already used in industry for manufacturing metals on a large scale, but uses...
For the first time ever, scientists have determined the cosmic origin of highest-energy neutrinos. A research group led by IceCube scientist Elisa Resconi, spokesperson of the Collaborative Research Center SFB1258 at the Technical University of Munich (TUM), provides an important piece of evidence that the particles detected by the IceCube neutrino telescope at the South Pole originate from a galaxy four billion light-years away from Earth.
To rule out other origins with certainty, the team led by neutrino physicist Elisa Resconi from the Technical University of Munich and multi-wavelength...
For the first time a team of researchers have discovered two different phases of magnetic skyrmions in a single material. Physicists of the Technical Universities of Munich and Dresden and the University of Cologne can now better study and understand the properties of these magnetic structures, which are important for both basic research and applications.
Whirlpools are an everyday experience in a bath tub: When the water is drained a circular vortex is formed. Typically, such whirls are rather stable. Similar...
Physicists working with Roland Wester at the University of Innsbruck have investigated if and how chemical reactions can be influenced by targeted vibrational excitation of the reactants. They were able to demonstrate that excitation with a laser beam does not affect the efficiency of a chemical exchange reaction and that the excited molecular group acts only as a spectator in the reaction.
A frequently used reaction in organic chemistry is nucleophilic substitution. It plays, for example, an important role in in the synthesis of new chemical...
Optical spectroscopy allows investigating the energy structure and dynamic properties of complex quantum systems. Researchers from the University of Würzburg present two new approaches of coherent two-dimensional spectroscopy.
"Put an excitation into the system and observe how it evolves." According to physicist Professor Tobias Brixner, this is the credo of optical spectroscopy....
13.07.2018 | Event News
12.07.2018 | Event News
03.07.2018 | Event News
20.07.2018 | Power and Electrical Engineering
20.07.2018 | Information Technology
20.07.2018 | Materials Sciences