Marker and co-therapy that inhibits succinate dehydrogenase to increase patient response to venetoclax.
- Co-therapy increases MM sensitivity to venetoclax treatment.
- Identifies patients who will respond to venetoclax therapy.
Multiple Myeloma (MM) is a cancer of plasma cells responsible for making antibody and fighting infection. It is the second most common blood cancer. Current treatments include immunomodulatory drugs, proteasome inhibitors and newer targeted therapies. Chemo-resistant MM is common, with approximately 20% of patients succumbing to aggressive treatment resistance disease shortly after diagnosis. VenclextaTM (ABT-199) is an orally bioavailable, selective BCL-2 antagonist that induces cell death in MM cells, particularly those exhibiting t(11;14) which comprises approximately 7% of MM. Therefore, methods to expand application of VenclextaTM for MM therapy are warranted.
Emory University researchers have determined that succinate ubiquinone reductase (SQR) activity predicts venetoclax sensitivity. Inhibiting SQR sensitizes resistant cells to venetoclax. The researchers have developed an activity assay to identify MM patients who will respond to venetoclax therapy; as well as have demonstrated efficacy of a combination therapy of venetoclax with an SQR inhibitor. This therapy can help improve the effectiveness of venetoclax therapy in MM.
SQR inhibitors are under development.