Novel Therapeutic Strategy for Head and Neck Cancer

Two 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 2 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, National Institute of Dental and Craniofacial Research (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. The data of 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 NIDCR 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.