RO4929097 + temozolomide

RO4929097 + temozolomide is an investigational combination therapy consisting of RO4929097, a small molecule oral gamma-secretase inhibitor that targets the Notch signaling pathway, and temozolomide, an alkylating chemotherapy agent. RO4929097 inhibits gamma-secretase, thereby blocking Notch receptor activation and downstream signaling involved in tumor cell proliferation, survival, and maintenance of cancer stem-like cells. Temozolomide induces DNA damage through methylation at the O6 and N7 positions of guanine residues in DNA, leading to apoptosis in rapidly dividing tumor cells. This combination has been studied primarily for its potential to treat malignant gliomas (including glioblastoma) and melanoma by targeting both bulk tumor cells (via temozolomide) and cancer stem-like cell populations (via Notch inhibition with RO4929097)[1][2][8]. Preclinical studies suggest synergistic effects between these agents[8].