In India, Hindus call a three-pronged spear a trishul. The prongs symbolize nature, in its creative, preservative, and destructive states. Cancer research aims are akin to those natural states. Rapid cellular division is the creative state, for which chemotherapy and radiation, (or most recently synchronous chemoradiation), are used to kill the rapidly dividing cells. Angiogenesis meets a preservative requirement, bringing blood flow to tumors. Metastasis is a resulting destructive oncogenic state.
Oncologist clinicians require an evolving therapy plan – a plan to wield like a specialized weapon to hit moving targets. Many clinical trials are now involving multiple drugs in synchronized or sequenced treatments. They hope to overcome obstacles like drug resistance…to promote synergistic drug actions…all to achieve improved patient outcomes.
HDAC inhibitors are important targets on the cancer battlefield for good reason. Here’s an example. Belinostat, also called PXD101 is a Class I and II histone deacytelase (HDAC) inhibitor, made by the Danish biotech company, Topotarget. Topotarget is partnered with Spectrum Pharmaceuticals in the US. The Topotarget web site lists eleven Phase II belinostat clinical trials in process, plus five Phase II completed. Its actions are selective yet multiple, including halting cellular division, apoptotic, anti-angiogenesis, promoting differentiation and re-sensitizing cancer cells to chemotherapies. Sounds formidable. The FDA has given it orphan drug status and a vote of confidence by putting the trial onto Fast Track. Results are to be completed for an application for authorization to the FDA, (U.S.A.), in early 2012.
Please click here for the E3 record of an open access review on HDAC inhibitors from the journal, Pharmaceuticals (Basel). At right, click on DOI under links and download the pdf.
Ellis L, & Pili R (2010). Histone Deacetylase Inhibitors: Advancing Therapeutic Strategies in Hematological and Solid Malignancies. Pharmaceuticals (Basel, Switzerland), 3 (8), 2411-2469 PMID: 21151768