Researchers at Yale School of Medicine have discovered 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. The finding, published in a study, could pave the way for more targeted treatments and allow clinicians to move from one-size-fits-all approaches to personalized therapies.
The team focused on two common types of gliomas: oligodendrogliomas and astrocytomas. They 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.
To gain insights into the biological mechanisms underpinning treatment-resistant gliomas, the researchers obtained paired brain cancer tissue samples from each of approximately 180 patients from around the world. The first sample was taken at diagnosis and the second when the cancer recurred. They then analyzed the DNA of the samples and compared the before and after 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 when 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.
The study’s implications extend beyond the lab. For clinicians, it underscores the potential of monitoring DNA mutations in recurrent tumors to guide treatment decisions. For patients, it offers hope that therapies can be adjusted before resistance fully develops, potentially extending survival. For the biotechnology industry, it signals a shift toward precision medicine in neuro-oncology, where therapies are tailored to the genetic profile of a tumor rather than its histological appearance. As research continues, the findings may also spur investment in diagnostic tools capable of detecting emerging mutations early. The research was disseminated by BioMedWire, a communications platform focused on biotechnology and life sciences, which is part of the Dynamic Brand Portfolio at IBN.
