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. The findings, 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 researchers focused on oligodendrogliomas and astrocytomas, common types of gliomas that afflict humans. They discovered 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 investigate, the team 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 view 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 implications of this research extend beyond the laboratory. If borne out in further studies, DNA-guided treatment could fundamentally alter how clinicians monitor and treat recurrent brain cancers, potentially extending survival for patients with these aggressive diseases. The findings also highlight the need for ongoing genomic surveillance in cancer care, a shift that would require new diagnostic tools and therapeutic strategies. As the scientific community grapples with these questions, the Yale study provides a crucial foundation for rethinking treatment resistance in brain cancer.
