Recently, TNFα-induced protein 3 (TNFAIP3, A20) was reported to prevent TRAIL-induced caspase 8 cleavage in the DISC by mediating ubiquitination of RIP1 in glioblastoma.
Successful treatment with a combination of anti-VEGFR2 and anti-PD-L1 antibodies induced high endothelial venules (HEVs) in PyMT (polyoma middle T oncoprotein) breast cancer and RT2-PNET (Rip1-Tag2 pancreatic neuroendocrine tumors), but not in glioblastoma (GBM).
By demonstrating that BV6 primes glioblastoma cells for TMZ in a NF-κB- and RIP1-dependent manner, these findings build the rationale for further (pre)clinical development of Smac mimetics in combination with TMZ.
RIP1 has recently been found to be overexpressed in glioblastoma multiforme, the most common adult primary malignant brain tumor, but not in grade II to III glioma.