Abstract
Glioblastoma remains profoundly challenging. Moreover, the unique genetic, epigenetic, and microenvironmental features of glioblastoma contribute to its resistance to current therapies, complicating the development of effective therapeutic strategies. Recurrence represents a significant obstacle, as residual cancer stem cells can survive initial therapies and lead to tumor regrowth, often in the same or more aggressive form. Herein, we aim to repurpose three bioactive compounds—fenbendazole, papain, and sodium selenite—as novel therapeutic agents for brain cancer. Fenbendazole, a benzimidazole anthelmintic, disrupts microtubule dynamics by binding to β-tubulin, inhibiting mitosis, reducing glucose uptake, and inducing apoptosis in rapidly dividing tumor cells. Papain, a cysteine protease derived from papaya, exhibits antitumor potential through the degradation of extracellular matrix components, modulation of immune responses, and promotion of apoptotic pathways. Sodium selenite, an inorganic selenium compound, selectively induces oxidative stress in cancer cells, triggering apoptosis and potentially enhancing sensitivity to conventional therapies. Our in vitro studies have demonstrated significant antitumor activity for each compound, as well as combinatorial synergies against several brain tumor cell lines in vitro. To translate these findings into a clinically actionable approach, we are developing an implantable, biodegradable scaffold capable of localized controlled release of these agents within the brain tumor resection cavity. This polyvinyl alcohol-based delivery system is designed to maximize therapeutic efficacy while minimizing systemic toxicity. By integrating these repurposed compounds within our novel biomaterial platform, our strategy offers a promising avenue for improving outcomes in patients with malignant brain tumors. It represents a potentially impactful advancement in neuro-oncology care.