In the ever-evolving landscape of cancer therapy, while cancer treatments such as chemotherapy, radiotherapy, and targeted therapy aim to eradicate malignant cells, they also inadvertently trigger cellular senescence in both cancerous and microenvironmental tissues. Therapy-induced senescence (TIS) can act as a barrier against tumor growth by halting cell proliferation in the short term, but the long-term persistence of therapy-induced senescent (TISnt) cells may pose a significant challenge in cancer management. Their distinct characteristics, like senescence-associated secretory phenotype (SASP), metabolic dysregulation, and immune evasion, make them exhibit remarkable heterogeneity to orchestrate the tumor microenvironment (TME), resulting in therapy resistance. However, how these TISnt cells functioning differently in cancer progression, and the intricate mechanisms by which they remodel the senescence-associated immunosuppressive microenvironment present challenges for improving anticancer therapy. Therefore, this review summarizes the heterogeneous TISnt cell phenotypes contributing to an accumulated senescent state, outlines their multidimensional interactions in the senescent microenvironment, and discusses current senescence-targeting strategies. Building on the current understanding of TIS, we propose potential avenues for improving TIS-targeting methodologies in the context of head and neck cancer, a representative heterogeneous malignancy, which can substantially enhance the efficacy of the “one-two punch” sequential treatment approach for head and neck cancer.

Oral potentially malignant disorders (OPMDs) are a group of diseases involving the oral mucosa and that have a risk of carcinogenesis. The microenvironment is closely related to carcinogenesis and cancer progression by regulating the immune response, cell metabolic activities, and mechanical characteristics. Meanwhile, there are extensive interactions between the microenvironments that remodel and provide favorable conditions for cancer initiation. However, the changes, exact roles, and interactions of microenvironments during the carcinogenesis of OPMDs have not been fully elucidated. Here, we present an updated landscape of the microenvironments in OPMDs, emphasizing the changes in the immune microenvironment, metabolic microenvironment, mechanical microenvironment, and neural microenvironment during carcinogenesis and their carcinogenic mechanisms. We then propose an immuno–metabolic–mechanical–neural interaction network to describe their close relationships. Lastly, we summarize the therapeutic strategies for targeting microenvironments, and provide an outlook on future research directions and clinical applications. This review depicts a vivid microenvironment landscape and sheds light on new strategies to prevent the carcinogenesis of OPMDs.

This study is the first time to assess the synergistic efficacy and safety of plaque control on erosive non-gingival oral lichen planus (OLP). A randomized, controlled, clinical trial with blind evaluation was designed, and 48 OLP patients with erosive non-gingival OLP lesions were randomly assigned to the experimental group (n = 25, receiving intralesional triamcinolone acetonide injection, periodontal scaling, and oral hygiene instruction) and the control group (n = 23, only receiving intralesional triamcinolone acetonide injection) once a week for 2 weeks. Erosion size, pain level, plaque index, and community periodontal index were measured at every visit. Patients cured of erosion were followed up for 3 months to evaluate the recurrence rate. Adverse reactions were also recorded. At day 14 ± 2, the experimental group showed a higher completely healed percentage of erosion, a greater reduction of erosion size and pain level. However, no significant difference was observed in the recurrence rate. No participants had any severe adverse reactions. In conclusion, an improvement was observed in patients with plaque control, and future studies with larger sample sizes are needed to reinforce the external validity of this study.