Killer compound pinpoints brain cancer but avoids normal cells

"We found an explanation for how acidic tumor environment enables the cancer cells to survive and evade chemotherapy, and at the same time, we found a drug candidate that blocks this survival pathway to selectively kill them without touching normal cells," Charles Hong says. (Credit: Getty Images)

Researchers have unveiled a potential game-changer in the fight against glioblastoma, the most common and currently incurable form of brain cancer.

Their weapon of choice? A drug-like compound named Ogremorphin, or OGM. In laboratory experiments, OGM showed a remarkable ability to kill glioblastoma cells while leaving normal cells unharmed.

The discovery is an “early but an extremely promising path to a cure,” says Charles Hong, chair of the department of medicine at Michigan State University College of Human Medicine, who led the study in the journal Experimental Hematology and Oncology.

What makes OGM special lies in its precision. The researchers targeted an acid sensor called GPR68/OGR1 on the cancer cell membranes, disrupting a crucial signaling pathway that cancer cells rely on to survive and grow.

“Because glioblastoma cells acidify their tumor environment and then use the acid sensing receptor to survive, the OGM compound essentially cuts off their lifeline,” Hong says. “We haven’t found a single brain cancer cell line that it can’t kill.”

Hong believes this groundbreaking research isn’t confined to glioblastoma alone. Since other cancer types are also known to acidify their tumor environment to thrive and evade traditional therapies, this discovery could lead to treatments targeting other types of cancer.

The reality of brain cancer is that, even with the standard treatment that combines brain surgery, chemotherapy, and radiation therapy, the median survival period is 15-18 months following diagnosis, with a five-year survival rate of around 10%. Such outcome is due to cancer recurrence and treatment resistance.

“We found an explanation for how acidic tumor environment enables the cancer cells to survive and evade chemotherapy, and at the same time, we found a drug candidate that blocks this survival pathway to selectively kill them without touching normal cells,” Hong says.

“This is a just first step,” he adds. “Developing a treatment for human glioblastoma patients will take years of research. We hope to have human trials within five years.”

Additional coauthors are from Michigan State, the University of Maryland School of Medicine, and the Johns Hopkins University School of Medicine.

Source: Michigan State