NQO1 (NAD(P)H: quinone oxidoreductase-1), located on chromosome 16q22, functions primarily to protect normal cells from oxidant stress and electrophilic attack. Recent studies have revealed that NQO1 is expressed at a high level in most human solid tumors including those of the colon, breast, pancreas, ovaries and thyroid, and it has also been detected following the induction of cell cycle progression and proliferation of melanoma cells. In this study, we aimed to investigate the clinicopathological significance of upregulated NQO1 protein expression in squamous cell carcinomas (SCCs) of the uterine cervix. The localization of the NQO1 protein was determined in the SiHa cervical squamous cancer cell line using immunofluorescence (IF) staining, and immunohistochemical (IHC) staining performed on paraffin-embedded cervical SCC specimens from 177 patients. For comparison, 94 cervical intraepithelial neoplasia (CIN) and 25 normal cervical epithelia samples were also included. QRT-PCR was performed on RNA from fresh tissues to detect NQO1 mRNA expression levels, and HPV infection status was genotyped using oligonucleotide microarray. Disease-free survival (DFS) and 5-year overall survival (OS) rates for all cervical SCC patients were calculated using the Kaplan–Meier method, and univariate and multivariate analysis was performed using the Cox proportional hazards regression model. The NQO1 protein showed a mainly cytoplasmic staining pattern in cervical cancer cells, and only three cases of cervical SCC showed a nuclear staining pattern. The strongly positive rate of NQO1 protein expression was significantly higher in cervical SCCs and CINs than in normal cervical epithelia. High-level NQO1 expression was closely associated with poor differentiation, late-stage, lymph node metastasis and high-risk for HPV infection. Additionally, high-level NQO1 expression was associated with lower DFS and 5-year OS rates, particularly for patients with early-stage cervical SCCs. Furthermore, Cox analysis revealed that NQO1 expression emerged as a significant independent hazard factor for DFS rate in patients with cervical SCC. NQO1 overexpression might be an independent biomarker for prognostic evaluation of cervical SCCs.

Colorectal cancer (CRC) continues to be a predominant cause of cancer-related mortality worldwide, with existing therapies constrained by systemic toxicity, resistance, and inadequate tumor targeting. While immunotherapy has potential in specific CRC subtypes, its overall effectiveness is still limited. The cyclic GMP‒AMP synthase-stimulator of interferon genes (cGAS‒STING) pathway, an essential cytosolic DNA sensor that facilitates innate immune responses, has surfaced as a prospective target for cancer immunotherapy. Recent studies have demonstrated that it plays dual roles in CRC: on the one hand, it triggers antitumor immune responses, while on the other hand, it promotes intestinal inflammation. Accurate delivery of STING agonists made feasible by developments in nanotechnology offers novel ways to modify the TME and overcome resistance. The current understanding of the activation and function of the cGAS-STING pathway in CRC, its impact on the TME, and recent developments in STING-targeted therapeutic approaches, comprising monotherapy and combination strategies with chemotherapy, radiotherapy, and immune checkpoint inhibitors, is summarized in this review. We also review new nanomedicine approaches designed to increase STING activation. Understanding the complex roles of cGAS-STING in CRC could help guide the development of next-generation immunotherapies with improved selectivity and efficacy.