Pioneering Pelotonia-Supported Studies at the OSUCCC – James
Gaining Insights Into Radiation Resistance in Brain Cancer
Radiation is often used to treat glioblastoma, the most lethal form of brain cancer. The treatment kills the great majority of the cells it strikes, but it usually can’t kill them all because radiation doses are limited by the need to minimize damage to healthy brain cells.
But in surviving glioblastoma cells, radiation treatment can trigger changes that promote tumor recurrence and make the cells resistant to further radiation therapy.
Why this happens is poorly understood, but a new study by OSUCCC – James researchers and supported in part by Pelotonia provides new and important insights into the cause of problem. It also identifies molecules that could be targeted by future drugs to perhaps prevent recurrence. The study by Divya Kesanakurti, PhD, a postdoctoral fellow working in the lab of Vinay Puduvalli, MBBS, professor of Neurology, director, Division of Neuro-Oncology, and colleagues, was published in the journal Oncogene.
The finding reveals molecular changes that lay the groundwork for tumor recurrence and radiation resistance in glioblastoma. It is known that radiation produces molecules in cells called reactive oxygen species that usually play an important role in killing cancer cells. But sustained levels of these molecules after radiation can promote tumor growth.
Kesanakurti and Puduvalli’s study found that glioblastoma cells that survive radiation have high levels of a molecule called PAK4. PAK4 then activates specific genes in tumor cells that increase reactive oxygen species and give the surviving cancer cells features of a more primitive and aggressive form of cell called a mesenchymal cell.
Glioblastoma cells that revert to this more primitive cell type grow faster and form tumors that are more aggressive and more resistant to radiation.
“Our results are the first evidence that PAK4 is involved in the radiation-induced transition of glioma cells to this more aggressive cell type, and they suggest that the therapeutic targeting of PAK4 might overcome radiation resistance in
Teaching the Tango to Improve Balance
Nearly four out of 10 cancer patients treated with multidrug chemotherapy develop nerve damage that can cause pain, numbness and muscle weakness in the extremities and impair balance.
Patients with this condition—called chemotherapy-induced peripheral neuropathy, or CIPN—often have impaired balance and difficulty standing and walking. CIPN often resolves a few months after chemotherapy ends, but until then, patients are at risk for injurious falls, and many use a cane or walker.
There are no good treatments for the condition, but Marie “Mimi” Lamantia, an Ohio State dance and pre-med major, received a 2015 Pelotonia Fellowship to study whether the Argentine tango might help cancer survivors return to their feet.
Lamantia’s mentors are Lise Worthen-Chaudhari, MFA, MS, research assistant professor in the College of Medicine, Department of Physical Medicine and Rehabilitation, and Maryam Lustberg, MD, assistant professor in the Division of Medical Oncology.
Lamantia has held 20 one-hour sessions of adapted Argentine tango (two one-hour sessions a week for 10 weeks), working with 31 cancer survivors and support givers. Balance was improved for the survivors who were at high risk for falling due to CIPN, as measured by biomechanical indicators of postural control.
Lamatia will present the findings at the 2016 American Congress of Rehabilitation Medicine in October.
“Using dance to help people with CIPN offers so much more than being in a doctor’s office doing balance exercises,” Lamantia says.
“I could see the improvement in these individuals, not only in the way they held themselves, but in their confidence when they walked into class,” she adds. “They were steadier. They were more at ease. It was really beautiful to see that over time.”