Gliobastoma is considered to be a fatal condition presumably due to its high resistance to therapies. Striving to combat this resistant mechanism, scientists from the Emory University have disclosed a new pathway for targeted medications that could aid the treatment of gliobastoma.
Initial methods relied on activating apoptosis or cell suicide by accessing remedial agents like tumor factor-related apoptosis-inducing ligand (TRAIL). However, the resistance encountered in the process apparently did not lead to successful treatment of the condition.
“Scientists in this field have been hoping to treat this cancer with this new type of apoptosis pathway-targeted therapeutic drug, and this new information may provide a path forward,” commented Chunhai ‘Charlie’ Hao, M.D., Ph.D., a neuropathologist at Emory University.
The team examined human gliobastoma specimens and cancerous stem cells that unleashed a new pathway to restrain the resistance experienced with apoptosis pathway-targeted therapeutic drugs.
Scientists believed that TRAIL treatment usually led to caspase-8-mediated apoptosis. But according to reports, the gene A20 E3 ligase seemed to be expressed substantially in gliobastomas. When this gene interacted with a receptor interacting protein (RIP1) and caspase-8, it appeared to result in the formation of a signaling complex.
When TRAIL interacted with the aforesaid complex, the A20 E3 ligase apparently stimulated ubiquitination of RIP1. The latter is a process that inhibits the working of TRAIL. Further, this process impeded the activation of caspase-8 and thus prohibited caspase-8-initiated apoptosis thereafter.
This research essentially showed how the RIP1 ubiquitination process can be altered to combat the resistance to apoptosis-targeted cancer medications. Therefore, A20 E3 ubiquitin ligase may be considered a new drug target for gliobastoma. Striking the ligase could help restrain resistance to TRAIL, the analysts concluded.
The findings are published in Cancer Discovery, the journal of the American Association for Cancer Research (AACR).