Abstract
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.
Highlights
Cancer in humans constitutes a set of about a hundred different diseases characterised by the uncontrolled growth of the affected cells often combined with the ability to spread, through metastasis, to distant sites
Target receptor distribution was investigated through examining a wide selection of cancer tissue types
Cancer cell lines derived from these tissues were found to express nfP2X7
Summary
Cancer in humans constitutes a set of about a hundred different diseases characterised by the uncontrolled growth of the affected cells often combined with the ability to spread, through metastasis, to distant sites. The search for one or more elusive magic bullets as proposed by the Nobel Laureate Paul Ehrlich and others over a century ago [1] was always predicated on the hope of identifying a common target or pathway Such a discovery would enable the apparent innate complexity in cancer to be greatly simplified. Of the 84 actively sought cancer targets in current development, the top 8 are the focus of about 235 of the drugs that are in advanced clinical development These include VEGFR, PI3K, HER2, EGFR, PDGFR, c-Kit, cMet and mTor. Targeting of up-regulated receptors or pathway components present on normal cells is sub-optimal given the propensity for such procedures to generate unwanted side effects. Specificity for the target is paramount, both for avoiding unwanted side effects and for minimising the required therapeutic dose that is otherwise lost through unwanted binding to normal (non-target) tissue
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