publication date: Aug. 3, 2017

Brain tumors

Experimental “enhancer” may boost conventional therapies for pediatric disease

Laboratory studies suggest that an experimental drug already in early clinical trials for a variety of adult cancers might enhance radiation and chemotherapy for two childhood brain cancers.

In a report on two studies conducted by Johns Hopkins Kimmel Cancer Center researchers, the drug, known as TAK228, suppressed the growth of human cancer cells cultured in the laboratory and significantly extended the lives of mice implanted with cells from the two cancers, diffuse intrinsic pontine glioma and atypical teratoid/rhabdoid tumors.

Johns Hopkins researchers and their colleagues, led by Eric Raabe, assistant professor of oncology and instructor of pathology at the Johns Hopkins Kimmel Cancer Center, focused their attention on TAK228.

Previous research showed the drug, also known as MLN0128, can cross the blood-brain barrier and reduces the production of a protein called mTOR, which appears to sustain cancer by combining with other proteins to signal the cells to grow, invade tissues and survive therapy.

Both pediatric cancer types typically have genetic alterations that lead to increases in mTOR activity, thus Raabe and his team’s hypothesis that TAK228 could be an effective treatment for these cancers.

In one set of experiments, Raabe and his colleagues applied the drug to cells of each cancer type isolated from human patients. Results showed that TAK228 reduced proliferation of DIPG cells cancer cells by about 30 percent compared with untreated cells and killed about 6 percent of the cells.

However, when combined with radiation — currently the most effective treatment for extending life in children with DIPG — nearly double the number of cells were killed compared with radiation alone, suggesting that TAK228 might sensitize cells to make radiation more effective, Raabe says.

When the team tested TAK228 … Continue reading CCL July 2017 – Experimental “enhancer” may boost conventional therapies for pediatric disease

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