ROS-Mediated Therapeutic Strategy in Chemo-/Radiotherapy of Head and Neck Cancer

Abstract

Head and neck cancer is a highly genetic and metabolic heterogeneous collection of malignancies of the lip, oral cavity, salivary glands, pharynx, esophagus, paranasal sinuses, and larynx with five-year survival rates ranging from 12% to 93%. Patients with head and neck cancer typically present with advanced stage III, IVa, or IVb disease and are treated with comprehensive modality including chemotherapy, radiotherapy, and surgery. Despite advancements in treatment modality and technique, noisome recurrence, invasiveness, and resistance as well as posttreatment complications severely influence survival rate and quality of life. Thus, new therapeutic strategies are urgently needed that offer enhanced efficacy with less toxicity. ROS in cancer cells plays a vital role in regulating cell death, DNA repair, stemness maintenance, metabolic reprogramming, and tumor microenvironment, all of which have been implicated in resistance to chemo-/radiotherapy of head and neck cancer. Adjusting ROS generation and elimination to reverse the resistance of cancer cells without impairing normal cells show great hope in improving the therapeutic efficacy of chemo-/radiotherapy of head and neck cancer. In the current review, we discuss the pivotal and targetable redox-regulating system including superoxide dismutases (SODs), tripeptide glutathione (GSH), thioredoxin (Trxs), peroxiredoxins (PRXs), nuclear factor erythroid 2-related factor 2/Kelch-like ECH-associated protein 1 (Nrf2/keap1), and mitochondria electron transporter chain (ETC) complexes and their roles in regulating ROS levels and their clinical significance implicated in chemo-/radiotherapy of head and neck cancer. We also summarize several old drugs (referred to as the non-anti-cancer drugs used in other diseases for a long time) and small molecular compounds as well as natural herbs which effectively modulate cellular ROS of head and neck cancer to synergize the efficacy of conventional chemo-/radiotherapy. Emerging interdisciplinary techniques including photodynamic, nanoparticle system, and Bio-Electro-Magnetic-Energy-Regulation (BEMER) therapy are promising measures to broaden the potency of ROS modulation for the benefit of chemo-/radiotherapy in head and neck cancer.

Critical signaling pathways governing hepatocellular carcinoma behavior; small molecule-based approaches

“…ROS can stimulate VEGF or the hypoxia pathway to promote angiogenesis in HCC [ 177 , 178 ] and mediates cell cycle activation and CSC maintenance in cancer [ 179 ]. ROS-mediated signaling events mediate chemoresistance to the cancer cells [ 180 ]. Though, excessive ROS can disrupt the proteins in mitochondria and promote the DNA mutations, causing the release of pro-apoptotic factors into the cytoplasm of the cancer cells [ 178 ].…”

HNC0014, a Multi-Targeted Small-Molecule, Inhibits Head and Neck Squamous Cell Carcinoma by Suppressing c-Met/STAT3/CD44/PD-L1 Oncoimmune Signature and Eliciting Antitumor Immune Responses

“…It is anticipated that less developed countries will experience an 80% increase in cancer-related deaths by 2025 [ 4 ]. Head and neck cancers (HNCs) are a heterogeneous metabolic and genetic collection of malignancies of the pharynx, oral cavity, paranasal sinuses, lips, salivary glands, esophagus, and larynx [ 5 ], which account for about 4.9% of all known cancer sites [ 6 ]. HNCs are the seventh most often occurring and ninth most fatal cancers [ 7 ], with 5-year survival rates ranging 12–93% [ 5 ].…”

“…Head and neck cancers (HNCs) are a heterogeneous metabolic and genetic collection of malignancies of the pharynx, oral cavity, paranasal sinuses, lips, salivary glands, esophagus, and larynx [ 5 ], which account for about 4.9% of all known cancer sites [ 6 ]. HNCs are the seventh most often occurring and ninth most fatal cancers [ 7 ], with 5-year survival rates ranging 12–93% [ 5 ]. In 2020, there were more than 84,000 new HNC cases and more than 30,000 deaths in the United States alone [ 5 ], and approximately 90% of HNC cells are pathologically squamous carcinomas (HNSCCs).…”

“…HNCs are the seventh most often occurring and ninth most fatal cancers [ 7 ], with 5-year survival rates ranging 12–93% [ 5 ]. In 2020, there were more than 84,000 new HNC cases and more than 30,000 deaths in the United States alone [ 5 ], and approximately 90% of HNC cells are pathologically squamous carcinomas (HNSCCs). Annual diagnoses were estimated to increase to about 833,000 new cases in 2020 [ 8 ].…”

“…Management of advanced HNSCC involves multiple treatment modalities such as surgery, chemotherapy, radiotherapy, and immunotherapy [ 13 ]. However, despite advancements in diagnoses and effective treatment modalities, such as intensity-modulated radiotherapy (IMRT), low-invasive transoral surgery, immunotherapy (anti-programmed death-ligand 1 (PD-L1) therapy), and drug targeting (anti-EGFR therapy) [ 5 ], overall survival (OS) rates of advanced-stage HNSCC patients have remained poor [ 8 ]. Lamentably, more than half of patients develop recurrence in distant or nearby sites within 24 months of treatment [ 14 , 15 ].…”