This technology is a method to delay or reduce temozolomide resistance in glioblastoma cancer patients, and can also be used to treat cancer in subjects with temozolomide resistance by reducing the degree of resistance.
Current standard treatments for glioblastoma multiforme (GBM) include chemotherapy using the DNA-alkylating agent temozolomide (TMZ) alongside surgical resection and irradiation. However, almost all GBM patients develop gradual resistance to TMZ due to increased expression of a DNA repair enzyme, O6-methylguanine-DNA methyltransferase (MGMT), in TMZ-treated tumor cells. MGMT reduces sensitivity to TMZ by removing the cytotoxic DNA lesions TMZ creates, thus rendering the treatment ineffective.
This technology identified an enhancer genetic element far from the MGMT gene that increases the expression of both MGMT and Ki67, a well-known marker for cell proliferation that is dysregulated in several cancer lines. The technology found that perturbing this enhancer using epigenetic small molecule drugs such as bromodomain inhibitors (BETi), or histone acetyltransferase inhibitors (HATi), increased the sensitivity of the cancer to TMZ. By combining the use of these agents with TMZ, this technology has been shown to slow tumor TMZ resistance or restore tumor sensitivity to TMZ, and therefore has the potential to improve the efficacy of GBM treatments.
This technology has been validated using patient-derived GBM xenograft cell lines.
Patent Pending (US20210060006)
IR CU18203
Licensing Contact: Joan Martinez