Cancer development and its response to therapy are regulated by inflammation, which either promotes or suppresses tumor progression, potentially displaying opposing effects on therapeutic outcomes. Chronic inflammation facilitates tumor progression and treatment resistance, whereas induction of acute inflammatory reactions often stimulates the maturation of dendritic cells (DCs) and antigen presentation, leading to anti-tumor immune responses. In addition, multiple signaling pathways, such as nuclear factor kappa B (NF-kB), Janus kinase/signal transducers and activators of transcription (JAK-STAT), toll-like receptor (TLR) pathways, cGAS/STING, and mitogen-activated protein kinase (MAPK); inflammatory factors, including cytokines (e.g., interleukin (IL), interferon (IFN), and tumor necrosis factor (TNF)-α), chemokines (e.g., C-C motif chemokine ligands (CCLs) and C-X-C motif chemokine ligands (CXCLs)), growth factors (e.g., vascular endothelial growth factor (VEGF), transforming growth factor (TGF)-β), and inflammasome; as well as inflammatory metabolites including prostaglandins, leukotrienes, thromboxane, and specialized proresolving mediators (SPM), have been identified as pivotal regulators of the initiation and resolution of inflammation. Nowadays, local irradiation, recombinant cytokines, neutralizing antibodies, small-molecule inhibitors, DC vaccines, oncolytic viruses, TLR agonists, and SPM have been developed to specifically modulate inflammation in cancer therapy, with some of these factors already undergoing clinical trials. Herein, we discuss the initiation and resolution of inflammation, the crosstalk between tumor development and inflammatory processes. We also highlight potential targets for harnessing inflammation in the treatment of cancer.

The year 2024 marks the 60th anniversary of the discovery of the Epstein-Barr virus (EBV), the first virus confirmed to cause human cancer. Viral infections significantly contribute to the global cancer burden, with seven known Group 1 oncogenic viruses, including hepatitis B virus (HBV), human papillomavirus (HPV), EBV, Kaposi sarcoma-associated herpesvirus (KSHV), hepatitis C virus (HCV), human T-cell leukemia virus type 1 (HTLV-1), and human immunodeficiency virus (HIV). These oncogenic viruses induce cellular transformation and cancer development by altering various biological processes within host cells, particularly under immunosuppression or co-carcinogenic exposures. These viruses are primarily associated with hepatocellular carcinoma, gastric cancer, cervical cancer, nasopharyngeal carcinoma, Kaposi sarcoma, lymphoma, and adult T-cell leukemia/lymphoma. Understanding the mechanisms of viral oncogenesis is crucial for identifying and characterizing the early biological processes of virus-related cancers, providing new targets and strategies for treatment or prevention. This review first outlines the global epidemiology of virus-related tumors, milestone events in research, and the process by which oncogenic viruses infect target cells. It then focuses on the molecular mechanisms by which these viruses induce tumors directly or indirectly, including the regulation of oncogenes or tumor suppressor genes, induction of genomic instability, disruption of regular life cycle of cells, immune suppression, chronic inflammation, and inducing angiogenesis. Finally, current therapeutic strategies for virus-related tumors and recent advances in preclinical and clinical research are discussed.

Radiation therapy (RT) has been employed as a tumoricidal modality for more than 100 years and on 470,000 patients each year in the United States. The ionizing radiation causes genetic changes and results in cell death. However, since the biological mechanism of radiation remains unclear, there is a pressing need to understand this mechanism to improve the killing effect on tumors and reduce the side effects on normal cells. DNA break and epigenetic remodeling can be induced by radiotherapy. Hence the modulation of histone modification enzymes may tune the radiosensitivity of cancer cells. For instance, histone deacetylase (HDAC) inhibitors sensitize irradiated cancer cells by amplifying the DNA damage signaling and inhibiting double-strand DNA break repair to influence the irradiated cells’ survival. However, the combination of epigenetic drugs and radiotherapy has only been evaluated in several ongoing clinical trials for limited cancer types, partly due to a lack of knowledge on the potential mechanisms on how radiation induces epigenetic regulation and chromatin remodeling. Here, we review recent advances of radiotherapy and radiotherapy-induced epigenetic remodeling and introduce related technologies for epigenetic monitoring. Particularly, we exploit the application of fluorescence resonance energy transfer (FRET) biosensors to visualize dynamic epigenetic regulations in single living cells and tissue upon radiotherapy and drug treatment. We aim to bridge FRET biosensor, epigenetics, and radiotherapy, providing a perspective of using FRET to assess epigenetics and provide guidance for radiotherapy to improve cancer treatment. In the end, we discuss the feasibility of a combination of epigenetic drugs and radiotherapy as new approaches for cancer therapeutics.

Background: The prognostic significance of non‐cancer‐related prognostic factors, such as body composition, has gained extensive attention in oncological research. Compared with sarcopenia, the prognostic significance of adipose tissue for overall survival in non‐small cell lung cancer remains unclear. We investigated the prognostic value of skeletal muscle and adipose tissue in patients with non‐small cell lung cancer.Methods: This retrospective study included 4434 patients diagnosed with non‐small cell lung cancer between January 2014 and December 2016. Cross‐sectional areas of skeletal muscle and subcutaneous fat were measured, and the pericardial fat volume was automatically calculated. The skeletal muscle index and subcutaneous fat index were calculated as skeletal muscle area and subcutaneous fat area divided by height squared, respectively, and the pericardial fat index was calculated as pericardial fat volume divided by body surface area. The association between body composition and outcomes was evaluated using Cox proportional hazards model.Results: A total of 750 patients (501 males [66.8%] and 249 females [33.2%]; mean age, 60.9 ± 9.8 years) were included. Sarcopenia (60.8% vs. 52.7%; P < 0.001), decreased subcutaneous fat index (51.4% vs. 25.2%; P < 0.001) and decreased pericardial fat index (55.4% vs. 16.5%; P < 0.001) were more commonly found in the deceased group than survived group. In multivariable Cox regression analysis, after adjusting for clinical variables, increased subcutaneous fat index (hazard ratio [HR] = 0.56, 95% confidence interval [CI]: 0.47–0.66, P < 0.001) and increased pericardial fat index (HR = 0.47, 95% CI: 0.40–0.56, P < 0.001) were associated with longer overall survival. For stage I–III patients, increased subcutaneous fat index (HR = 0.62, 95% CI: 0.48–0.76, P < 0.001) and increased pericardial fat index (HR = 0.43, 95% CI: 0.34–0.54, P < 0.001) were associated with better 5‐year overall survival rate. Similar results were recorded in stage IV patients. For patients with surgery, the prognostic value of increased subcutaneous fat index (HR = 0.60, 95% CI: 0.44–0.80, P = 0.001) and increased pericardial fat index (HR = 0.51, 95% CI: 0.38–0.68, P < 0.001) remained and predicted favourable overall survival. Non‐surgical patients showed similar results as surgical patients. No association was noted between sarcopenia and overall survival (P > 0.05).Conclusions: Increased subcutaneous fat index and pericardial fat index were associated with a higher 5‐year overall survival rate, independent of sarcopenia, in non‐small cell lung cancer and may indicate a reduced risk of non‐cancer‐related death.

Background and purpose: Stereotactic body radiotherapy (SBRT) is a promising ablative modality for hepatocellular carcinoma (HCC) especially for those with small-sized or early-stage tumors. This study aimed to synthesize available data to evaluate efficacy and explore related predictors of SBRT for small liver-confined HCC (≤ 3 lesions with longest diameter ≤ 6 cm). Materials and methods: A systematic search were performed of the PubMed and Cochrane Library databases. Primary endpoints were overall survival (OS) and local control (LC) of small HCC treated with SBRT, meanwhile, to evaluate clinical parameters associated with treatment outcome by two methods including subgroup comparisons and pooled HR meta-analysis. The secondary endpoint was treatment toxicity. Results: After a comprehensive database review, 14 observational studies with 1238 HCC patients received SBRT were included. Pooled 1-year and 3-year OS rates were 93.0% (95% confidence interval [CI] 88.0–96.0%) and 72.0% (95% CI 62.0–79.0%), respectively. Pooled 1-year and 3-year LC rates were 96.0% (95% CI 91.0–98.0%) and 91.0% (95% CI 85.0–95.0%), respectively. Subgroup comparisons regarding Child–Pugh class (stratified by CP-A percentage 100%, 75–100%, 50–75%) showed there were statistically significant differences for both 1-year and 3-year OS rate (p < 0.01), while that regarding number of lesions, pretreatment situation, age (median/mean age of 65), macrovascular invasion, tumor size, and radiation dose (median BED₁₀ of 100 Gy), there were no differences. In subgroup comparisons for LC rate, it showed number of lesions (1 lesion vs. 2–3 lesions) was significantly associated with 1-year LC rate (p = 0.04), though not associated with 3-year LC rate (p = 0.72). In subgroup comparisons categorized by other factors including pretreatment situation, age, CP-A percentage, macrovascular invasion, tumor size, and radiation dose, there were no significant differences for 1- or 3-year LC rate. To further explore the association between CP class and OS, the second method was applied by combining HR and 95% CIs. Results indicated CP-A was predictive of better OS (p = 0.001) with pooled HR 0.31 (95% CIs 0.11–0.88), which was consistent with subgroup comparison results. Concerning adverse effect of SBRT, pooled rates of grade ≥ 3 hepatic complications and RILD were 4.0% (95% CI 2.0–8.0%) and 14.7% (95% CI 7.4–24.7%), respectively. Conclusion: The study showed that SBRT was a potent local treatment for small liver-confined HCC conferring excellent OS and LC persisting up to 3 years, even though parts of included patients were pretreated or with macrovascular invasion. CP-A class was a significant predictor of optimal OS, while number of lesions might affect short term tumor control (1-year LC). Tumor size and radiation dose were not vital factors impacting treatment outcome for such small-sized HCC patients. Because of the low quality of observational studies and heterogeneous groups of patients treated with SBRT, further clinical trials should be prospectively investigated in large sample sizes.