As shown in the new study, this drug combo unblocked what are referred to as ‘don’t eat me pathways’ that prevent macrophages in the immune system from consuming a tumor.
In a breakthrough discovery, scientists at the University of Colorado Anschutz Medical Campus have found a promising drug combination that could improve the outlook for children diagnosed with MYC amplified Medulloblastoma, a particularly lethal type of brain cancer.
This research was carried out in partnership with the German Cancer Consortium (DKTK) and University Hospital Dusseldorf.
These tumors are particularly aggressive due to an oncogene called MYC which makes them more likely to recur and spread to “other parts of the brain and down the spine,” according to lead author Siddhartha Mitra.
Currently, “the five-year survival rate for this type of cancer is less than 45%”.
“We wanted to discover better treatment options for these kids.”
Mitra and his team found that a combination of two drugs, both of which had already passed phase I safety trials for other types of solid tumors, had a significant impact on MYC-amplified Medulloblastoma.
Through the use of the epigenetic drug tacedinaline, the researchers discovered that MYC not only causes the tumors to grow, but also makes them invisible to the immune system’s cells.
By doing so, they were able to remove barriers in the immune system’s “don’t eat me pathways,” which normally prohibit macrophages from eating a tumor.
Then, they made the tumor more attractive to the immune system.
When we used tacedinaline to unblock those pathways, and then added anti-CD47, a drug which makes macrophages become super eaters, the tumor became extremely appetizing to the macrophages enticing them to eat the tumor that was unblocked,” Mitra said. “You are essentially harnessing the body’s own immune system by giving it a jumpstart, much like a medical version of PacMan.”
By using “tacedinaline to unblock these pathways,” and then administering “anti-CD47,” a drug that increases the ability of macrophages to consume tumors, they made the tumor highly appealing to the immune system’s cells, encouraging them to attack and destroy it, according to the lead author.
“You are essentially harnessing the body’s own immune system by giving it a jumpstart, much like a medical version of PacMan.”
While conventional treatments like chemotherapy have historically targeted the tumor growth pathways, according to Mitra, this is the first time that the immune evasion pathways are being targeted in these kinds of deadly brain tumors.
Conventional adult cancer treatments are not effective in children as their bodies are still growing and their healthy cells divide quickly, according to Mitra.
“This drug combination” has the potential to not only reduce the negative side effects of “traditional cancer treatments” in children, but also increase the survival rate for patients “diagnosed with MYC amplified Medulloblastoma”.
The next stage, according to him, would be a clinical study to ascertain the treatment’s immediate and long-term benefits.
Image Credit: Getty