Mitochondria in Overdrive Linked to Glioblastomas
Mitochondria, often referred to as the powerhouses of the cell, help turn the energy we take from food into energy that the cell can use. Mitochondria are also involved in signaling between cells and cell death, heat production, and signaling calcium. A new study by cancer scientists at Columbia University’s Vagelos College of Physicians and Surgeons and Herbert Irving Comprehensive Cancer Center, has found that up to 20% of glioblastomas are powered by overactive mitochondria and may be treatable with drugs currently in clinical trials.
Their study was published in Nature Cancer in a paper titled, “Pathway-based classification of glioblastoma uncovers a mitochondrial subtype with therapeutic vulnerabilities.”
“We can now expand these clinical trials to a much larger group of patients, because we can identify patients with mitochondria-driven tumors, regardless of the underlying genetics,” stated Antonio Iavarone, MD, professor of neurology, who led the study with Anna Lasorella, MD, professor of pediatrics.
Glioblastoma is the most common primary brain tumor in adults. Median survival for individuals with glioblastoma is 15 months.
The study found that all brain cancers fall into one of four groups, including the mitochondrial subtype.
The researchers gained new insights into what drives each subtype and the prognosis for patients by classifying brain cancers based on their core biological features. They characterized the biological properties of 17,367 individual cells from 36 different tumors.
Using the data, the researchers devised a computational approach to identify core biological processes, or pathways, in the cells rather than the more common approach of identifying gene signatures. “In this way, we can classify each individual tumor cell based on the real biology that sustains them,” Iavarone explained.
“Existing classifications for brain cancer are not informative. They don’t predict outcomes; they don’t tell us which treatments will work best,” Lasorella noted.
The researchers classified glioblastoma in four biological groups. Two of them summarize functions active in the normal brain, either stem cells or neurons. The other two groups include mitochondrial tumors and a group of tumors with multiple metabolic activities that are resistant to current therapies.
“We are excited about the mitochondrial group because we have drugs for that group in clinical trials already,” Lasorella said, “but the classification now gives us ideas about how to target these other three and we are starting to investigate these more intensely.”
“We’re going beyond one mutation, one drug concept,” she said. “Sometimes it’s possible to get a response that way. But it’s time to target tumors based on the commonalities of their core biology, which can be caused by multiple different genetic combinations.”
Lasorella and Iavarone are now applying a “pan-cancer” approach by applying the same techniques to different aggressive cancers, which may lead to treating different mitochondrial types of cancers.
“When we classify based on the cell’s core biological activities, which all cells rely on to survive and thrive, we may find that cancers share more in common than was previously apparent by just looking at their genes,” concluded Lasorella.