SummaryPatients with glioblastoma die from local relapse despite surgery and high-dose radiotherapy. Resistance to radiotherapy is thought to be due to efficient DNA double-strand break (DSB) repair in stem-like cells able to survive DNA damage and repopulate the tumor. We used clinical samples and patient-derived glioblastoma stem cells (GSCs) to confirm that the DSB repair protein RAD51 is highly expressed in GSCs, which are reliant on RAD51-dependent DSB repair after radiation. RAD51 expression and RAD51 foci numbers fall when these cells move toward astrocytic differentiation. In GSCs, the small-molecule RAD51 inhibitors RI-1 and B02 prevent RAD51 focus formation, reduce DNA DSB repair, and cause significant radiosensitization. We further demonstrate that treatment with these agents combined with radiation promotes loss of stem cells defined by SOX2 expression. This indicates that RAD51-dependent repair represents an effective and specific target in GSCs.

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The SMART Course can give orthopedic surgeons in LMICs the skills and knowledge to successfully perform flaps, reducing the self-reported incidence of amputations. Course participants were able to disseminate flap reconstructive techniques to colleagues at their home institution. While this course offers a collaborative, sustainable approach to reduce global surgical disparities in amputation, future investigation into the viability of teaching the SMART course in LMICs is warranted.

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