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

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.

Peroxisome proliferator-activated receptorα/γ agonist pioglitazone for rescuing relapsed or refractory neoplasias by unlocking phenotypic plasticity

“…These hubs might serve as organized access for tumor tissue editing schedules, also for pioglitazone as immune modulator, inflammation inhibitor, metabolic regulator and differentiation inducer ( 172 ). Particularly, proteomic platforms may enable to test differentiation induction or inflammation control and to uncover ways for edited non-oncogene addiction in a highly personalized manner ( 20 , 29 , 173 ).…”

“…Tissue editing techniques include synergistic combinations of bioactive drugs, such as metronomic low-dose chemotherapies, transcriptional modulators, i.e., pioglitazone, interferon-α, dexamethasone or all-trans retinoic acid (ATRA) and cyclooxygenase-2 (COX-2) inhibitors, and may induce long-term tumor control, objective response, even continuous complete remission (cCR) in r/r neoplasias ( 21 – 23 , 25 – 28 ). On the top, edited stress reponse pathways, referred to as non-oncogene addiction in tumor tissues, provide a novel, repurposed activity profile for approved targeted therapies ( 20 , 29 ).…”

Chloride intracellular channels in oncology as potential novel biomarkers and personalized therapy targets: a systematic review

“…Personalized therapies are becoming accessible due to extensive investigation of cancer biomarkers and targeted treatment [1]. Worldwide research leads to the development of combinatorial therapies targeting multiple cancer-associated processes [2]. A comprehensive investigation of tumor microenvironment (TME) increases the number of possible diagnostic and therapeutic targets [3].…”

PRI-724 and IWP-O1 Wnt Signaling Pathway Inhibitors Modulate the Expression of Glycolytic Enzymes in Tongue Cancer Cell Lines

“…Its occurrence depends on both genetic and epigenetic abnormalities, and in a subset of cases, it is caused by human papillomavirus (HPV) infection. Importantly, HPV-negative HNSCC tumors present a worse prognosis and higher diversity in molecular changes, for instance, in the activity of pro-tumorigenic signaling pathways [7]. The significance of particular hallmarks of cancer among HNSCC differs, and not all are experimentally well-proven [8].…”