New Approach to Brain Tumors: Cut the Motor

    It’s tough to hit a fast-moving target — especially if it’s microscopic and lodged deep in a person’s densely packed and highly sensitive brain.

    Yet that is the challenge doctors face in treating the cells of glioblastoma tumors, the most common and aggressive type of cancerous brain tumors.

    Why glioblastoma can be so deadly

    Glioblastoma tumors attack critical parts of the brain and account for nearly half of all brain tumors. Because the brain is dense, it is challenging for most cancer cells to grow and spread there. But glioblastoma cells manage to grow and spread to surrounding tissue quickly, making traditional treatments like radiation and chemotherapy largely ineffective.

    That translates to bad outcomes for many patients. “Glioblastoma has had a notoriously poor prognosis,” says Steven Rosenfeld, MD, PhD, a Cleveland Clinic neuro-oncologist. Average survival following diagnosis is 12 months, even with treatment. Without treatment, average survival is four months.

    Finding what motors the tumors

    Proteins in brain cancer cells (blue) act as “motors” to propel the cells through dense brain tissue, allowing a brain tumor to quickly move and spread.

    So, rather than focusing only on killing a moving target, researchers are trying to make the target stop moving altogether.

    Cleveland Clinic researchers helped discover what makes glioblastoma cells move so well in dense brain tissue: tiny molecular “motors” known as nonmuscle myosin IIA and IIB. These proteins are referred to as motors because they supply the cells with bursts of energy.

    Here’s what happens: A tumor cell extends a long “finger” of cell matter to force its way through the narrow pathways between healthy brain cells (see image). Then the tumor cell’s motors kick in, causing the rear of the cell to contract. That propels the bigger cell body through the pathways, allowing the tumor to spread.

    The motor proteins are found at high levels in glioblastoma tumor cells but not in normal brain tissue cells. “This makes the motors a potentially ideal target for new drug development,” says Dr. Rosenfeld.

    The goal: Stopping tumors in their tracks

    That development is already underway. Laboratory experiments and mouse studies of glioblastoma have shown that fasudil, a drug used in Japan for unrelated illnesses, shows promise in its ability to turn off the motors in glioblastoma cells.

    “Throwing a wrench into the works of these motors — by preventing or interfering with their activity — stops the cells from moving,” explains Dr. Rosenfeld, who is conducting some of these studies. “This promises to open the door to a new area of drug development for glioblastoma.”

    He adds that researchers are also studying approaches that combine therapies that switch off the motors with existing treatments, such as radiation and chemotherapy, designed to kill the tumor cells altogether.

    “The hope is to one day offer patients with glioblastoma a treatment strategy that not only stops tumor cell development and growth but literally stops it in its tracks,” says Dr. Rosenfeld.

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