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Despite therapies like surgery, radiotherapy, and chemotherapy, GBM results in poor survival rates, with a median survival of just 1 year. This has led to the need for more effective treatment options with fewer side effects. The study aims to explore the mechanisms behind GBM and highlight the potential of natural bioactive compounds, either alone or in combination with conventional therapies, to provide synergistic effects. Several small natural molecules, such as resveratrol, curcumin, rutin, and icariin, have shown promising anticancer and apoptotic properties in drug\u2010resistant and p53\u2010mutant GBM cell lines. These compounds enhance the antitumor effects of temozolomide (TMZ), targeting glioma stem cells, reducing oxidative stress, preventing cell proliferation, triggering apoptosis, and impeding oncogenic processes. 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