Some brain tumors, such as glioblastomas – the most common and invasive brain tumors in humans – are more prevalent in men than women and are often more harmful, but the reasons behind this have been unclear. Now, researchers from Washington University in St. Louis, MO, may have shed some light on the issue.
In a study published in The Journal of Clinical Investigation, the researchers reveal that a protein associated with reduced cancer risk – retinoblastoma protein (RB) – is much less active in the brain cells of men than women.
Dr. Joshua Rubin and colleagues began their research by conducting a series of experiments on a cell model of glioblastoma. This involved exposing male and female brain cells to a tumor growth factor and a number of genetic alterations.
From this, the team confirmed that tumors grow faster and more frequently from male brain cells than they do from female brain cells.
To try and determine the mechanisms behind this, the researchers analyzed three genes – neurofibromin, p53 and RB – that normally lower tumor development by curbing cell division and survival. The researchers note that in many cancers, these particular genes are disabled or mutated.
Dr. Rubin and colleagues found that, compared with female brain cells, the RB protein was significantly more likely to be inactivated in male brain cells.
Furthermore, they found that disabling the RB protein in female brain cells caused them to be just as susceptible to cancer than the male brain cells.
Dr. Rubin says these findings may have important implications for treating patients with brain tumors and identifying those at risk:
“This is the first time anyone ever has identified a sex-linked difference that affects tumor risk and is intrinsic to cells, and that’s very exciting.
These results suggest we need to go back and look at multiple pathways linked to cancer, checking for sex differences. Sex-based distinctions at the level of the cell may not only influence cancer risk but also the effectiveness of treatments.”
He adds that as well as brain tumors, there are other cancers – such as some liver cancers – that are more common in men than women.
“Knowing more about why cancer rates differ between males and females will help us understand basic mechanisms in cancer, seek more effective therapies and perform more informative clinical trials.”
RB is currently being evaluated as a drug target in clinical trials. Researchers are attempting to trigger the anti-tumor effects of the protein in the hope it will prolong survival of cancer patients.
But Dr. Rubin says the team’s findings should prompt the researchers of these trials – and those involved in other trials – to look at data in a different way.
“In clinical trials, we typically examine data from male and female patients together, and that could be masking positive or negative responses that are limited to one sex,” he explains. “At the very least, we should think about analyzing data for males and females separately in clinical trials.”
Last month, Medical News Today reported on a study published in Nature Communications, which claimed to reveal one reason why glioblastomas spread so rapidly. The team found that the cancer cells hijack and feed off the brain’s blood vessels, weakening the blood-brain barrier.