New Finding: Overactive Mitochondria Are Responsible for Twenty Percent of Glioblastoma Brain Cancers

Neuroscience News recently carried an article heralding reports of researchers’ finding that upwards of twenty percent of lethal glioblastoma brain cancers may be treatable by newly developed drugs.

Currently, the median survival for glioblastoma patients is fifteen months.

Tests are being conducted on these new drugs to treat patients who have been diagnosed with a rare gene fusion (accidental joining of DNA of two genes) that also fuels overactive mitochondria.

Researchers Identify a New Type of Glioblastoma

Researchers at Columbia University found that glioblastomas are affected by overactive mitochondria, which are normally responsible for creating the energy to power cells. But in the case of glioblastomas, the tumor cells were found to survive on the additional energy that overactive mitochondria provide.

The team classified brain cancers under one of four subtypes, including the mitochondrial subtype. Two of the subtypes are replicas of active functions in a normal brain. The third category includes the newly identified mitochondrial tumors. The fourth group exhibits metabolic activities that are extremely resistant to available therapies.

The new classification of brain cancers is based on biological (the process that occurs in living things) features.

These categories no longer simply highlight cell biomarkers or genetic alterations but now focus on the newly discovered drivers of each subtype and patient prognosis.

Note that a yet unpublished addition to the online Nature Cancer study of January 11, 2021, involved the newly developed drugs and their efficacy against mitochondrial tumors in glioblastomas affecting lab animals.

Study Co-leaders Offer Clarification

According to study co-leader Dr. Antonio Iavarone, categorizing the subtypes will allow the expansion of clinical trials because patients will be identified according to the mitochondria-driven tumors rather than genetics.

Dr. Iavarone led the study with Dr. Anna Lasorella, members of the Institute for Cancer Genetics at Columbia. Dr. Lasorella added that the current classifications of brain cancer do not predict outcomes or indicate which treatments would be most effective.

Dr. Lasorella emphasized the importance of the new mitochondrial subtype which allows the researchers to rely on the drugs that are already in clinical trials.

She explained that the new classification leads to ideas in targeting the other three groups. Intensive investigations in these areas have already begun. Dr. Lasorella said that their new approach is to move out of the one drug concept and one mutation. She said that now they intend to target tumors according to commonalities of the tumor’s biology. Multiple genetic combinations can be responsible for these mutations.

Dr. Iavarone stated that he believes that a lack of an accurate classification of brain tumors explains why brain cancer therapeutics have not progressed at a faster pace.

The team observed that patients in the mitochondrial group were found to have a somewhat better prognosis by surviving a few months longer than patients in the other three groups.

Well-Defined and Effective Subtypes

Breast cancer’s subtypes are well-defined. They are specific examples of an accurate classification system that led to the creation of targeted therapies. Examples of breast cancer’s critical hallmarks would be HER2 or estrogen receptors that involve specific subtypes.

About Single Cell Analysis

Single cell-by-cell analysis was used in the mitochondrial study. Scientists were able to analyze the activity of 17,367 cells within thirty-six tumors. The researchers found that most of the tumors were affected by cells associated with one of the four subtypes, with only a few cells from the other three subtypes.

The scientists used this data to identify pathways in those cells instead of the usual approach where they identified gene signatures. Dr. Iavarone said that by using this method they can classify individual tumor cells in accordance with the real biology that supports them.

The scientists believe that this new approach should recognize commonalities of various types of cancer regardless of the origin of the tumor. With these common pathways, drugs that treat mitochondrial brain cancer can also treat mitochondrial types of lung cancer.