Brain cancers that return after treatment do not simply regrow from residual tissue; they evolve through mutations that differ sharply depending on the cancer subtype, according to a new study from Yale School of Medicine. The findings, published in study, could reshape how clinicians select therapies for gliomas, the most common type of brain cancer in adults.
The research focused on two common gliomas: oligodendrogliomas and astrocytomas. For years, scientists assumed these cancers recur because surgery and other treatments fail to eliminate all malignant cells, and the surviving tissue regrows more aggressively. But the biological reasons for that increased aggression had remained unclear.
To investigate, the Yale team analyzed paired tissue samples from approximately 180 patients worldwide. One sample was taken at initial diagnosis, the other when the cancer returned. By comparing DNA before and after recurrence, the researchers found that the two sets of tumors had mutations that differed radically, and those differences were specific to the glioma subtype.
Astrocytomas developed DNA copy-number changes, including deletions or extra copies of entire genome sections. Oligodendrogliomas, by contrast, developed many single-point mutations in cancer genes. Although the two cancers looked similar under phenotypic examination, they diverged markedly at the DNA level. The team concluded that as these brain cancers become more resistant to treatment, they develop a variety of mutations that differ from one type of brain cancer to another.
The implication is significant: treatment strategies should focus more on the DNA of the cancers rather than targeting the phenotype when selecting therapies. If patients are monitored for DNA mutations and treatment is adjusted proactively, resistance could potentially be avoided. The researchers are now asking whether those mutations can be predicted and acted upon before they occur, which could extend survival for brain cancer patients well beyond current expectations.
That question is likely to weigh on cancer therapy developers such as Calidi Biotherapeutics Inc. (NYSE American: CLDI), which are pursuing R&D programs aimed at transforming how brain cancers are treated. The challenge adds to existing hurdles, including the blood-brain barrier, which prevents most treatments from reaching the brain.
The findings, reported by BioMedWire, a specialized communications platform focused on biotechnology and life sciences, underscore a broader shift toward personalized medicine in oncology. BioMedWire is one of more than 75 brands within the Dynamic Brand Portfolio at IBN, which provides wire solutions through InvestorWire and offers editorial syndication to 5,000+ outlets. For patients and investors alike, the Yale study signals that the next generation of brain cancer treatments may depend less on how tumors look and more on what their DNA reveals.
