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MS Drug May Be Effective in Treating Brain Cancer

Written by: | news@biospace.com | Dated: Monday, August 12th, 2019

 

Sanofi’s MS Drug May Be Effective in Treating Brain Cancer

 

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Glioblastoma is an aggressive brain cancer, the most common form of brain cancer. It makes up 16% of all brain malignancies. It is considered rare, affecting 3 out of 100,000 people in the U.S., with 13,000 new cases each year. It is aggressive, spreading throughout the brain, but for reasons not understood, does not metastasize outside the brain.

Glioblastoma is very difficult to treat and there have been several recent clinical trial failures for new drugs. However, recent research by scientists at the University of California San Diego School of Medicine in mice took a unique approach that shows a lot of promise. In addition to targeted cancer therapy, they used the multiple sclerosis (MS) drug teriflunomide, which is marketed under the brand name Aubagio by Sanofi. The research was published in the journal Science Translational Medicine.

“We used to think we’d find a single magic bullet to treat everyone with glioblastoma,” stated Jeremy Rich, senior author and director of neuro-oncology and director of the Brain Tumor Institute at UC San Diego Health. “But now we realize that we need to find out what drives each patient’s unique tumor, and tailor our treatments to each individual.”

The researchers note that even when traditional chemotherapy and radiation kill off most of a patient’s glioblastoma cells, they don’t always destroy the cancer stem cells. This allows the cancer to return indefinitely.

Conducting the research on mice with glioblastoma tumor cells implanted from brain cancer patients, they found that the glioblastoma cells shrank significantly when exposed to both Aubagio and a targeted cancer drug, BKM-120 (buparlisib). In 2018, Novartis transferred most of the worldwide rights to BKM-120 to Chinese company Adlai Noryte.

Aubagio works by blocking pyrimidine-forming enzymes. Glioblastoma cells need to continue making more DNA, which requires pyrimidine, a DNA building block. The researchers analyzed genomic data on hundreds of glioblastoma patients in six different databases and found that patients with higher pyrimidine metabolism had poorer survival.

“It’s a lot of hard work to be a cancer cell,” Rich stated. “They have to work all the time to find ways to pull together pathways to survive and grow. Not that I have sympathy for them. But knowing this helps us know where they might have weak spots.”

Rich and his research team tested two targeted cancer drugs, BKM-120, which is most effective in glioblastoma cells that lack the PTEN enzyme, and lapatinib, which is most effective in treating cancers with mutations in the Epidermal Growth Factor Receptor (EGFR). Using BKM-120 alone, the tumors decreased moderately, and the mice had longer survival times, compared to either placebo-treated mice or teriflunomide-treated mice. Lapatinib is marketed as Tykerb by Novartis.

However, when dosed with both Aubagio and BKM-120, tumors showed a much more significant shrinkage with significantly longer survival.

“We’re excited about these results, especially because we’re talking about a drug that’s already known to be safe in humans,” Rich stated. “But this laboratory model isn’t perfect—yes it uses human patient samples, yet it still lacks the context a glioblastoma would have in the human body, such as interaction with the immune system, which we know plays an important role in determining tumor growth and survival. Before this drug could become available to patients with glioblastoma, human clinical trials would be necessary to support its safety and efficacy.

Numerous researchers and biopharma companies will undoubtedly be interested. In May, AbbVie halted its Phase III INTELLANCE-1 clinical trial of depatuxizumab mafodotin (Depatux-M) in glioblastoma tumors with EGFR amplification because of lack of survival benefit. And about a week earlier, Bristol-Myers Squibb’s checkpoint inhibitor Opdivo (nivolumab) failed to meet its primary endpoint in newly diagnosed O6-methylguanine-DNA methyltransferase (MGMT)-unmethylated glioblastoma multiforme (GBM).

 

 

BioSpace source:

https://www.biospace.com/article/sanofi-s-ms-drug-may-be-effective-in-treating-brain-cancer

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