Novel Drug Candidate Shows Promise in Combatting Aggressive Brain Tumors by Targeting Cellular Motors

Researchers at the University of Florida's Wertheim UF Scripps Institute have developed an innovative experimental drug, MT-125, that offers new hope for treating glioblastoma, one of the most aggressive brain cancers. The study, published in the journal Cell, demonstrates that MT-125 can sensitize tumors to radiation and chemotherapy while preventing their invasion into surrounding tissues.

Glioblastoma affects approximately 14,000 individuals annually in the United States, with a median survival of just over a year despite conventional treatments like surgery, radiation, and chemotherapy. Notably, about half of these tumors do not respond to existing therapies, underscoring a critical need for new approaches. Dr. Courtney Miller and her team focused on the cellular 'motors' known as myosin proteins, which are nanoscale proteins that generate movement within cells by converting energy into mechanical work. These motors are involved in essential cellular functions such as movement, connection, and contraction, and are present in various tissues, including the brain.

The team designed a range of small molecules, led by medicinal chemist Theodore Kamenecka, to inhibit myosin motors selectively. Their breakthrough came with MT-125, which showed remarkable efficacy in preclinical models. In animal studies, MT-125 was capable of converting resistant glioblastoma cells into radiation-sensitive ones and inducing multinucleated cells that are marked for self-destruction. Additionally, the drug impeded the tumor cells' ability to change shape and invade new areas.

When combined with existing chemotherapy agents like sunitinib, a kinase inhibitor, MT-125 produced a powerful synergistic effect, leading to prolonged disease-free periods in mice. Though promising, the researchers acknowledged that many drugs effective in animals fail in human trials due to biological differences. To address safety, the team employed pulsed dosing, exploiting the higher sensitivity of cancer cells to MT-125 while minimizing toxicity to healthy tissue.

The compound, now licensed to Myosin Therapeutics, is advancing toward clinical trials following FDA approval, with the goal to establish MT-125 as a first-line treatment for glioblastoma. The scientists also envision potential applications against other cancers and malignant gliomas. Moreover, parallel efforts are underway to develop MT-110, a related compound targeting methamphetamine cravings, highlighting the broad therapeutic potential of myosin inhibitors.

This research exemplifies innovative and out-of-the-box thinking in cancer therapy development, aiming to transform prognosis for patients with devastating brain cancers. Although further studies are needed, MT-125 represents a significant step toward more effective treatments in neuro-oncology.

Source: Medical Xpress