Drugs to Treat Head and Neck Cancers: Mechanisms of Action

This chapter presents the anticancer agents used for the treatment of head and neck squamous cell carcinomas (HNSCC), emphasizing the mechanisms of action of the various drug classes. Current therapies for HNSCC can be broadly divided into four categories: (1) DNA damaging agents, (2) Antimetabolites that interfere with DNA synthesis, (3) Antimitotic agents that interfere with cell division, (4) Agents that target pathways whose dysregulation are critical for tumorigenesis, including apoptosis and angiogenesis. Agents from the first three groups interfere with cell division and are therefore fundamentally non-selective. Most of their significant adverse effects result from the damage they inflict on normal cells that divide or remodel rapidly. Targeted therapies in contrast have greater potential to selectively inhibit transformed cells while sparing normal tissues. All HNSCC therapies are affected by resistance mechanisms that decrease drug efficacy. Typical mechanisms of tumor resistance include reduced drug uptake, increased drug efflux, rapid metabolism, and overexpression/mutation of target enzymes and receptors. Resistance can be pre-empted using combination chemotherapy regimens in which several anticancer agents are given simultaneously. These agents are also used in multimodal therapies, i.e. as a complement to surgery and/or radiation. Indeed, most HNSCC is treated with multimodal therapy and combination chemotherapy. Intravenous injection is the typical route of administration, however a few can be given orally. We also discuss several compounds in various stages of investigation.