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अमूर्त

Non-Functional P2X₇: A Novel and Ubiquitous Target in Human Cancer

Julian A. Barden, Aysen Yuksel, John Pedersen, Suzanne Danieletto and Warick Delprado

The World Health Organisation reports there were 14.1 million new cancer cases and 8.2 million cancer deaths in 2012 demonstrating significant unmet medical needs exist. Modifications to cell death mechanisms that take place during cancer and the significant proliferative and metastatic potential of cancer cells have focused medical research onto targets and pathways that are known to control these critical functions. One such target is the P2X₇ receptor. P2X₇ is a purinergic receptor that forms ATP-gated channels ultimately mediating proliferation or cell death, depending on activation conditions. Recent preclinical studies have investigated the possibility that modulators of the P2X₇ channel may provide innovative cancer therapeutic approaches. The P2X₇ receptors expressed on cancer cells are found in a non-functional conformation we define as nfP2X₇. The nfP2X₇ receptor is unable to form the large pore conformation of the channel that is associated with driving cell death. In the present study we utilise antibodies that are specific to the nfP2X₇ form of P2X₇ to confirm the expression of nfP2X₇ receptor in a panel of human cancer tissues. We demonstrate that the nfP2X₇ is expressed ubiquitously on the surface of cancer cells and thus has potential to provide a novel and broad therapeutic cancer target.