Investigators, from left, Samir Parekh, MD; and Deepak Perumal, PhD
Research into a novel treatment that could help extend the lives of patients with multiple myeloma—a disease in which cancerous blood cells proliferate in the bone marrow—is being advanced by scientists at The Tisch Cancer Institute at the Icahn School of Medicine at Mount Sinai, who recently identified a new drug target called ARK5.
The Mount Sinai scientists discovered that when ARK5 is targeted simultaneously with CDK4, a pathway widely known to have a role in inhibiting multiple myeloma, the results were extremely effective in causing cell death. Their findings were published in the March 15, 2016, issue of the journal Cancer Research.
“Just targeting one cellular pathway hasn’t worked,” says the study’s principal investigator Samir Parekh, MD, Associate Professor of Medicine (Hematology and Medical Oncology), and Oncological Sciences at the Icahn School of Medicine at Mount Sinai. “Our novel findings showed there was a powerful and synergistic antimyeloma effect by the inhibition of CDK4 and ARK5 proteins.”
In their research, Dr. Parekh, and the study’s lead author Deepak Perumal, PhD, a postdoctoral scientist in Hematology and Medical Oncology, successfully tested a promising small molecule drug known as ON123300 that is capable of blocking both proteins. The drug—previously shown to be highly sensitive to breast cancer, mantle cell lymphoma, and a form of brain cancer—was developed by Onconova Therapeutics, Inc. USA, in collaboration with E. Premkumar Reddy, PhD, Director of Experimental Therapeutics at the Icahn School of Medicine at Mount Sinai.
ON123300 showed that it was able to kill cancer cells with great precision, making it highly distinguishable from prior drugs that focused on inhibiting cell cycle regulators such as CDKs that were able to halt disease progression but could not completely destroy malignant cells.
“There have been numerous studies on CDK4 inhibitors, but most of them have failed because of high toxicity and lack of selectivity,” says Dr. Perumal. “We want to learn more about the underlying biology of multiple myeloma so that we can see improvements in new therapeutic treatments for this disease.”
In the next stage of development, the researchers plan to test the novel drug in a clinical setting.
The American Cancer Society estimates that 30,330 new cases of multiple myeloma will be diagnosed in 2016, and 12,650 deaths will result from the disease, in which cancerous blood cells prevent the normal production of antibodies, leaving the body’s immune system weakened and susceptible to further disease. Current treatment involves a combination of drug therapy and bone marrow transplantation.
The Tisch Cancer Institute’s renowned Multiple Myeloma Program, led by Sundar Jagannath, MD, Professor of Medicine (Hematology and Medical Oncology), is the largest of its kind in New York City, and draws myeloma patients from around the world. The program specializes in the treatment of the most severe cases of multiple myeloma in patients who have failed multiple therapies.
“These now are the patients who can be targeted by new agents,” says Dr. Perumal.