Advantages of the Combinatorial Molecular Targeted Therapy of Head and Neck Cancer—A Step before Anakoinosis-Based Personalized Treatment

SIMPLE SUMMARY: Head and Neck Squamous Cell Carcinoma (HNSCC) is a major threat to public health around the world. Its occurrence is linked to genetic events and environmental factors, including Human Papilloma Virus (HPV) infections. Patients with HPV-positive tumors usually have a better prognosis than those with HPV-negative tumors. According to advances in understanding the molecular basis of HNSCC tumors, targeted therapy is thought to improve treatment outcomes. This article discusses the most important molecular targets for HNSCC and primarily demonstrates various perspectives on combinatorial molecular targeted therapy. Disruption of cancer cell signaling and microenvironmental homeostasis, targeting epigenetic modulators, energy metabolism, or oxidative stress are all common elements in anakoinosis-based therapy, which is a therapy that targets cancer cell intercellular and intracellular communication. Thus, those concepts have been described as potential ways to improve the prognosis of HPV-negative patients. ABSTRACT: The molecular initiators of Head and Heck Squamous Cell Carcinoma (HNSCC) are complex. Human Papillomavirus (HPV) infection is linked to an increasing number of HNSCC cases, but HPV-positive tumors generally have a good prognosis. External factors that promote the development of HPV-negative HNSCC include tobacco use, excessive alcohol consumption, and proinflammatory poor oral hygiene. On a molecular level, several events, including the well-known overexpression of epidermal growth factor receptors (EGFR) and related downstream signaling pathways, contribute to the development of HNSCC. Conventional chemotherapy is insufficient for many patients. Thus, molecular-based therapy for HNSCC offers patients a better chance at a cure. The first molecular target for therapy of HNSCC was EGFR, inhibited by monoclonal antibody cetuximab, but its use in monotherapy is insufficient and induces resistance. This article describes attempts at combinatorial molecular targeted therapy of HNSCC based on several molecular targets and exemplary drugs/drug candidates. The new concept of anakoinosis-based therapy, which means treatment that targets the intercellular and intracellular communication of cancer cells, is thought to be the way to improve the clinical outcome for HNSCC patients. The identification of a link between molecular targeted therapy and anakoinosis raises the potential for further progress in HPV-negative HNSCC therapy.