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Novel Therapeutic Strategy for Head and Neck Cancer

July 19, 2010

TSA induced hyperacetylation of histone H3 in head and neck squamous cell carcinoma cellsTwo are better than one.  So say generations of musicians, marriage counselors, and, more recently, medical oncologists.  The latter claim builds on the fact that chemotherapy drugs collectively target multiple biological factors unique to tumor cells.  By combining two drugs with different biological targets, it’s possible to produce a synergistic and thus more deadly one-two punch against tumor cells. 

In the July issue of the journal Molecular Cancer Therapy, NIDCR grantees and colleagues report early results of such a synergism in the treatment of head and neck squamous cell carcinoma.  The work builds on the earlier discovery that a novel proteasome-inhibitor called PS-341 induces programmed cell death, or apoptosis, in laboratory studies with cultured tumor cells.  But several research groups have shown that the drug’s potent effect seems to stall in clinical studies with certain tumor types, suggesting other cell signaling pathways kick into action, override the apoptotic signal, and allow tumor cells to survive.   This unexpected outcome led to further brainstorming and ultimately reports that the simultaneous administration of PS-341 (also called bortezomib) and another type of chemotherapeutic agent called a histone deacetylase inhibitor might restore the apoptotic signal.  In the current study, the researchers show this to be the case for head and neck squamous cell carcinoma and pinpoint the biochemical action that allows the apoptosis to proceed.  They conclude the synergistic combination of PS-341 and a histone deacetylase inhibitor, in this case trichostatin A, represents a potential novel therapeutic strategy for treating this common form of head and neck cancer.   

  • PS-341 and histone deacytelase inhibitor synergistically induce apoptosis in head and neck squamous cell carcinoma cells.  Kim J, Guan J, Chang I, Chen X, Han D, Wang CY.  Mol Cancer Ther. 2010 Jul;9(7):1977-84. Epub 2010 Jun 22.


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This page last updated: February 26, 2014