Researchers at Yale School of Medicine have found that as brain cancers become more resistant to treatment, they develop a variety of mutations that differ from one type of brain cancer to another. This study could pave the way for developing more targeted treatments and allowing clinicians to switch from one-size-fits-all approaches to more personalized therapies.
The researchers focused on oligodendrogliomas and astrocytomas, common types of gliomas that afflict humans. The team found that as these sub-categories of brain cancer become more aggressive, they develop mutations that are radically different.
For a long time, scientists have worked based on the thinking that these cancers recur because surgery and other forms of treatment are unable to remove or kill all the cancerous tissues. The residual tissues therefore regrow, but it hasn’t been clear why the subsequent tumors are more aggressive.
The researchers at Yale School of Medicine sought to get insights into the biological mechanisms underpinning the aggressive gliomas that resist treatment.
For their study, the team obtained paired brain cancer tissue samples from each of approximately 180 patients from around the world. The first sample was taken at the time when the brain cancer had just been diagnosed while the second was extracted when the cancer recurred.
They then analyzed the DNA of the samples and compared the before and after cancer recurrence mutations. They found that the two sets had mutations that differed radically, and those differences tended to be specific to the subtype of glioma.
Astrocytomas developed DNA copy-number changes involving deletions or extra copies of entire genome sections, while oligodendrogliomas developed many single-point mutations in cancer genes. While both kinds of cancer looked similar when examined from the point of their phenotype, they markedly differed when compared from the perspective of their DNA.
This suggests that treatment approaches should focus more on the DNA of the cancers instead of targeting the phenotype while selecting treatment options. In this way, treatment resistance could be avoided if patients are monitored for DNA mutations and the treatment is adjusted proactively to address those DNA changes observed.
The big question that the researchers have for the scientific community is whether those mutations can be predicted and acted upon before they happen so that brain cancer patients can survive for a lot longer than they currently do.
That is a big question that cancer therapy developers like Calidi Biotherapeutics Inc. (NYSE American: CLDI) are likely to ponder as they conduct their R&D programs geared at transforming the way cancers affecting the brain are treated. This challenge adds to existing cancer therapy hurdles, such as how to get past the blood-brain barrier that prevents most treatments from reaching the brain.
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