Molecularly targeted agents and immunotherapy for the treatment of head and neck squamous cell cancer (HNSCC).

Squamous cell carcinoma is one of the most frequent tumors of the head and neck and often presents at an advanced-stage. Traditionally, treatment for head and neck squamous cell carcinoma (HNSCC) has included surgery, radiation, and chemotherapy depending on both the site and stage of disease. Although the treatment approach for local disease is often standardized, the management of recurrent and advanced disease is evolving. A better understanding of the molecular mechanisms of HNSCC has led to numerous promising investigations and the push for the development of novel therapies. Similarly, over the past several decades, growing data supports the notion that an individual's immune system can be manipulated in such a way to help eradicate cancer. The success of immunotherapeutic agents such as interleukin therapy and immune checkpoint inhibitor blockade in cancer, particularly advanced-stage melanoma, has stimulated researchers to uncover similar success stories in HNSCC. Examples of immunotherapeutics that are being studied for the treatment of HNSCC include adoptive T-cell therapy, vaccines, and immune checkpoint inhibitor proteins (e.g., anti-CTLA-4, -PD-1, -PD-L1). Molecularly targeted agents of interest include inhibitors of transmembrane growth factor receptors, angiogenesis, and PI3K/AKT/mTOR and NOTCH signaling pathways. To date, cetuximab, an epidermal growth factor receptor inhibitor, is the only targeted agent for HNSCC that was approved by the Federal Food and Drug Administration (FDA) on the basis that it improves overall survival when combined with chemotherapy or radiation. Herein, the authors provide an up-to-date review of immunotherapeutic and molecularly targeted agents for the treatment of HNSCC.