Oral squamous cell carcinomas: state of the field and emerging directions.

Oral squamous cell carcinoma (OSCC) develops on the mucosal epithelium of the oral cavity. It accounts for approximately 90% of oral malignancies and impairs appearance, pronunciation, swallowing, and flavor perception. In 2020, 377,713 OSCC cases were reported globally. According to the Global Cancer Observatory (GCO), the incidence of OSCC will rise by approximately 40% by 2040, accompanied by a growth in mortality. Persistent exposure to various risk factors, including tobacco, alcohol, betel quid (BQ), and human papillomavirus (HPV), will lead to the development of oral potentially malignant disorders (OPMDs), which are oral mucosal lesions with an increased risk of developing into OSCC. Complex and multifactorial, the oncogenesis process involves genetic alteration, epigenetic modification, and a dysregulated tumor microenvironment. Although various therapeutic interventions, such as chemotherapy, radiation, immunotherapy, and nanomedicine, have been proposed to prevent or treat OSCC and OPMDs, understanding the mechanism of malignancies will facilitate the identification of therapeutic and prognostic factors, thereby improving the efficacy of treatment for OSCC patients. This review summarizes the mechanisms involved in OSCC. Moreover, the current therapeutic interventions and prognostic methods for OSCC and OPMDs are discussed to facilitate comprehension and provide several prospective outlooks for the fields.

Redox signaling in drug-tolerant persister cells as an emerging therapeutic target.

Drug-tolerant persister (DTP) cells have attracted significant interest, given their predominant role in treatment failure. In this respect, DTP cells reportedly survive after anticancer drug exposure, and their DNA repair mechanisms are altered to enhance adaptive mutation, accounting for the emergence of drug-resistant mutations. DTP cells resume proliferation upon treatment withdrawal and are responsible for cancer relapse. Current evidence suggests that DTP cells mediate redox signaling-mediated cellular homeostasis by developing various adaptive mechanisms, especially metabolic reprogramming that promotes mitochondrial oxidative respiration and a robust antioxidant process. There is an increasing consensus that disrupting redox homeostasis by intervening with redox signaling is theoretically a promising therapeutic strategy for targeting these sinister cells. In this review, we provide a comprehensive overview of the characteristics of DTP cells and the underlying mechanisms involved in redox signaling, aiming to provide a unique perspective on potential therapeutic applications based on their vulnerabilities to redox regulation.

Repurposing antifungal drugs for cancer therapy.

BACKGROUND: Repurposing antifungal drugs in cancer therapy has attracted unprecedented attention in both preclinical and clinical research due to specific advantages, such as safety, high-cost effectiveness and time savings compared with cancer drug discovery. The surprising and encouraging efficacy of antifungal drugs in cancer therapy, mechanistically, is attributed to the overlapping targets or molecular pathways between fungal and cancer pathogenesis. Advancements in omics, informatics and analytical technology have led to the discovery of increasing "off-site" targets from antifungal drugs involved in cancerogenesis, such as smoothened (D477G) inhibition from itraconazole in basal cell carcinoma. AIM OF REVIEW: This review illustrates several antifungal drugs repurposed for cancer therapy and reveals the underlying mechanism based on their original target and "off-site" target. Furthermore, the challenges and perspectives for the future development and clinical applications of antifungal drugs for cancer therapy are also discussed, providing a refresh understanding of drug repurposing. KEY SCIENTIFIC CONCEPTS OF REVIEW: This review may provide a basic understanding of repurposed antifungal drugs for clinical cancer management, thereby helping antifungal drugs broaden new indications and promote clinical translation.