May 26, 2022

A new approach to therapy-resistant tumors targets a specific cell-death pathway

Posted by in category: biotech/medical

In a paper appearing in Nature today, an international group of scientists report a new way to kill hard-to-treat cancers. These tumors resist current immunotherapies, including those using Nobel Prize-winning checkpoint-blocking antibodies.

The approach exploits Z-DNA. Rather than twisting to the right like B-DNA, Z-DNA has a left-handed twist. One role for Z-DNA is to regulate the to viruses. The response involves AADR1 and ZBP1, two proteins that specifically recognize Z-DNA. They do so through a Zα domain that binds to the Z-DNA structure with high affinity.

The Zα domain was originally discovered by Dr. Alan Herbert of InsideOutBio, a communicating author on the paper. The ADAR1 Zα domain turns off the , while the other ZBP1 Zα turns on pathways that kill virally infected , as previously shown by Dr. Sid Balachandran, the other communicating author on the paper. The interactions between ADAR1 and ZBP1 determine whether a cell lives or dies.

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