IIT Bombay Study Reveals Why Deadly Brain Cancer Returns After Treatment

Mumbai: Scientists at the Indian Institute of Technology (IIT) Bombay have identified a key reason why glioblastoma, one of the deadliest forms of brain cancer, almost always returns after treatment. The study found that the softness of brain tissue, and not just genetic changes, can make recurring tumours more aggressive and reveal drug targets that conventional laboratory methods fail to detect.

The research, led by Prof. Abhijit Majumder of IIT Bombay in collaboration with researchers from the Advanced Centre for Treatment, Research and Education in Cancer (ACTREC), Tata Memorial Centre, challenges the long-standing practice of studying cancer cells on rigid plastic laboratory dishes.

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Glioblastoma is a fast-growing brain tumour that is difficult to treat and often recurs even after surgery, radiation and chemotherapy. Patients usually survive only six months to a year after diagnosis, while recurrent tumours are typically more invasive and resistant to treatment.

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In a study published in Matrix Biology, researchers recreated tumour relapse by exposing glioblastoma cells to radiation, leaving only the treatment-resistant cells alive. When these surviving cells were implanted into the brains of mice, they formed more aggressive tumours than the original cancer cells, closely mirroring what doctors observe in patients. However, when the same cells were grown on standard plastic laboratory dishes, they appeared no different from the original tumour cells, masking the biological differences.

To mimic the real brain environment, the team grew the cells on specially engineered soft hydrogels—gel-like materials that match the softness of brain tissue. On these surfaces, recurrent tumour cells became more invasive and mobile, closely resembling relapsed tumours seen in patients.

"The rigid surface didn't just suppress the cells' aggressive behaviour; it completely erased the distinction between primary and recurrent tumour cells," said Prof. Shilpee Dutt, who collaborated on the study.

The researchers also identified PLEKHA7, a protein that appeared only when cancer cells were grown on brain-like soft gels and was found at higher levels in recurrent patient tumours. Blocking PLEKHA7 significantly reduced tumour growth and spread.

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In follow-up studies, the team found that NEAT1, a gene-regulating RNA molecule that controls genes linked to tumour growth, spread and treatment resistance, became highly active in the brain's soft environment. Reducing NEAT1 levels slowed tumour growth and made three-dimensional tumoroids—miniature laboratory-grown tumours that closely resemble real cancers—less invasive. Similar findings in breast and lung cancer models suggest that the physical environment influences cancer behaviour across multiple cancer types.

"If someone has a cancer drug target, they should include soft gels and tumoroids as an initial experiment," said Prof. Majumder, adding that more realistic laboratory models could improve cancer drug discovery and help address the nearly 90% failure rate of cancer drugs that show promise in laboratory studies but fail in human clinical trials.

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