PFKFB INHIBITORS IN SOLID TUMORS
REDUCING CANCER’S ENERGY SUPPLY AND INHIBITING DNA REPAIR
Most tumors of more than a couple of millimeters in size lack oxygen, because formation of blood vessels does not match tumor growth.
Kancera’s project is based on specific inhibition of the enzyme PFKFB3, whose inhibition is expected to starve and weaken the tumor cells. The result is reduced metabolism and cell growth in oxygen-deficient cancers. This overcomes the problem of tumors’ resistance to radiotherapy and chemotherapy, which are most effective against growing cells.
Since PFKFB3 is mainly found in tissues occasionally exposed to oxygen deficiency, there is good reason to assume that Kancera’s PFKFB3-targeted drug will primarily affect the tumor while healthy tissue is less affected.
The DNA repair system is also a target for Kancera’s PFKFB inhibitors.
PFKFB3 is elevated in radiotherapy-resistant patients. It is inhibited by KAN0438757 resulting in impaired DNA repair, limited new DNA synthesis and reduced recovery from radiation-induced cell cycle arrest in cancer cells.