Cancer Biology & Medicine最新文献

Intra-tumoral bacteria are pivotal in the initiation and progression of head and neck squamous cell carcinoma (HNSCC), exerting a significant influence on tumor cell biology, immune responses, and the tumor microenvironment (TME). Different types and distribution of bacteria threaten the balance of metabolism and the immune environment of tumor cells. Taking advantage of this disrupted homeostasis, intra-tumoral bacteria stimulate the secretion of metabolites or influence specific immune cell types to produce inflammatory or chemokines, thereby influencing the anti-tumor immune response while regulating the level of inflammation and immunosuppression within the TME. Some intra-tumoral bacteria are used as diagnostic and prognostic markers in clinical practice. Based on the unique characteristics of bacteria, the use of engineered bacteria and outer membrane vesicles for drug delivery and biological intervention is a promising new therapeutic strategy. The presence of intra-tumoral bacteria also makes chemoradiotherapy tolerable, resulting in a poor treatment effect. However, due to the immune-related complexity of intra-tumoral bacteria, there may be unexpected effects in immunotherapy. In this review the patterns of intra-tumoral bacteria involvement in HNSCC are discussed, elucidating the dual roles, while exploring the relevance to anti-tumor immune responses in the clinical context and the prospects and limitations of the use of bacteria in targeted therapy.

Objective: Immune checkpoint inhibitors (ICIs) have demonstrated substantial efficacy in patients with advanced non-small cell lung cancer (NSCLC). However, the optimal duration of ICI therapy remains unclear, and limited real-world data are available. The aim of this study was to evaluate the relationship between ICI therapy duration and overall survival (OS) in patients who achieved varying best overall response (BOR) during ICI treatment, and to compare patients treated for 6 to 18 months vs. at least 18 months.

Methods: This retrospective cohort study included adult patients diagnosed with advanced NSCLC who received ICI therapy at the Zhejiang Cancer Hospital between 2017 and 2022. Data collection ended on May 1, 2024, and statistical analysis was performed between May and June 2024.

Results: Using strict entry criteria, we screened 487 patients with advanced NSCLC and identified 134 eligible patients. Among these patients, the median durations of immunotherapy and follow-up were 24.57 months and 43.60 months, respectively. The objective response rate (ORR) was 58.2%, and the median progression-free survival (PFS) was 10.6 months. Median OS was not reached. At the last follow-up, 54 patients had no disease progression, and 118 patients remained alive. Patients treated with ICI therapy for ≥ 18 months had superior survival to those treated for 6 to 18 months (P = 0.039). Further analysis revealed that the survival benefit was associated with BOR during ICI therapy. Specifically, patients achieving complete response/partial response (CR/PR) who received ≥ 18 months of ICI therapy had a trend toward longer median OS than those treated for 6 to 18 months, but the difference did not reach statistical significance (P = 0.177). Patients with stable disease (SD) who received ≥ 18 months of ICI therapy had a statistically longer median OS than those treated for 6 to 18 months (P = 0.019). Among patients treated with ICIs for ≥ 18 months, 24 continued with ICI-based therapy and achieved a median PFS₂ of 6.67 months, an ORR of 33.3%, and a disease control rate (DCR) of 83.3%.

Conclusions: This study provides real-world evidence and novel insights into the need for continuing ICI therapy beyond 18 months in patients with advanced NSCLC who do not exhibit progressive disease. For patients achieving SD during ICI therapy, a treatment duration of at least 18 months appears appropriate. For patients achieving CR/PR, treatment decisions should be individualized according to patient-specific circumstances. However, owing to the retrospective study design, potential selection bias and confounding factors might have influenced the results. Therefore, our findings require further validation in prospective clinical studies.

Objective: Lung cancer is the most common cause of cancer-related deaths worldwide. Platinum-based chemotherapy is one of the main treatment options for patients with non-small cell lung cancer (NSCLC) but the effectiveness of chemotherapy is encumbered by drug resistance. Therefore, understanding the molecular mechanisms underlying chemotherapy resistance is crucial in improving treatment outcomes and prognosis.

Methods: The cell viability assay and apoptosis were used to analyze chemoresistance. Western blot analysis and wound healing testing were used to evaluate the epithelial-to-mesenchymal transition (EMT). Immunoprecipitation was used for analysis of protein modification. Promoter activity was determined using the luciferase reporter assay. Immunofluorescence staining was used to determine reactive oxygen species levels. The expression patterns of EMT markers and carnitine palmitoyltransferase 1C (CPT1C) were determined by Western blot analysis.

Results: CPT1C, which was shown to be highly expressed in lung cancer, is associated with cisplatin resistance in NSCLC cells. CPT1C depletion increased NSCLC cell sensitivity to cisplatin, while overexpression of CPT1C increased NSCLC cell resistance to cisplatin. Induction of EMT mediated CPT1C-induced cisplatin resistance. Ectopic expression of Snail reversed the increase in cisplatin sensitivity triggered by CPT1C knockdown. Moreover, CPT1C was shown to be regulated at the post-translational level and an E3-ubiquitin ligase, NEDD4L, was shown to be a major regulator of CPT1C stability and activity.

Conclusions: These data provide evidence for the first time that the lipid metabolism enzyme, CPT1C, mediates resistance to chemotherapy. Therefore, the use of combination therapy with a CPT1C inhibitor may be a promising new avenue in lung cancer treatment.

The diverse radiation types in medical treatments and the natural environment elicit complex biological effects on both cancerous and non-cancerous tissues. Radiation therapy (RT) induces oncological responses, from molecular to phenotypic alterations, while simultaneously exerting toxic effects on healthy tissue. N⁶-methyladenosine (m⁶A), a prevalent modification on coding and non-coding RNAs, is a key epigenetic mark established by a set of evolutionarily conserved enzymes. The interplay between m⁶A modification and radiobiology of cancerous and non-cancerous tissues merits in-depth investigation. This review summarizes the roles of m⁶A in the biological effects induced by ionizing radiation and ultraviolet (UV) radiation. It begins with an overview of m⁶A modification and its detection methods, followed by a detailed examination of how m⁶A dynamically regulates the sensitivity of cancerous tissues to RT, the injury response in non-cancerous tissues, and the toxicological effects of UV exposure. Notably, this review underscores the importance of novel regulatory mechanisms of m⁶A and their potential clinical applications in identifying epigenetically modulated radiation-associated biomarkers for cancer therapy and estimation of radiation dosages. In conclusion, enzyme-mediated m⁶A-modification triggers alterations in target gene expression by affecting the metabolism of the modified RNAs, thus modulating progression and radiosensitivity in cancerous tissues, as well as radiation effects on normal tissues. Several promising avenues for future research are further discussed. This review highlights the importance of m⁶A modification in the context of radiation biology. Targeting epi-transcriptomic molecules might potentially provide a novel strategy for enhancing the radiosensitivity of cancerous tissues and mitigating radiation-induced injury to normal tissues.

Oncolytic virotherapy (OVT) is a promising option for cancer treatment. OVT involves selective oncolytic virus (OV) replication within cancer cells, which triggers anti-tumor responses and immunostimulation. Despite promising potential, OVT faces critical challenges, including insufficient tumor-specific targeting, which results in limited tumor penetration and variability in therapeutic efficacy. These challenges are particularly pronounced in solid tumors with complex microenvironments and heterogeneous vascularization. A comprehensive research program is currently underway to develop and refine innovative delivery methods to address these issues to enhance OVT precision and efficacy. A principal area of investigation is the utilization of cellular carriers to enhance the delivery and distribution of OVs within tumor microenvironments, thereby optimizing immune system activation and maximizing anti-tumor effects. This review offers a comprehensive overview of the current strategies that are being used to enhance the delivery of OVs via cellular carriers with the goal of improving the clinical impact of OVT in cancer therapy.

Objective: Esophageal cancer (EC) ranks eighth among cancers in cancer-related deaths globally, and ~44% of new cases occur in China. We sought to describe the clinical characteristics and treatment landscape of EC in China before the approval of immunotherapy in 2020.

Methods: CHANNEL was a large, retrospective study using patient-level data from 14 hospitals/cancer centers across China, including adults initiating therapy for newly diagnosed EC (January to December 2018). Demographics, clinicopathologic characteristics, and treatment patterns over 6 months were descriptively summarized.

Results: Of 3,493 patients, 75.7% were men, the mean age was 64.1 years, and 75.0% had no family history of cancer. Most (92.8%) had squamous cell carcinoma, with a primary lesion in the middle esophagus (56.4%). Among patients with resectable EC, 92.9% received initial surgery, and 7.1% received neoadjuvant therapy, primarily chemotherapy (85.5% platinum-taxane). Among patients with unresectable early or locally advanced EC, 50.8% and 49.2% received palliative and radical therapy, respectively, as the initial treatment, primarily chemotherapy (66.5% platinum-taxane) and chemoradiotherapy (50.8% platinum-taxane), respectively. Adjuvant therapy was administered to 22.9% of patients undergoing initial surgery, and 2.4% receiving neoadjuvant therapy and surgery. Among patients with advanced EC, 84.6% received systemic therapy as an initial treatment, primarily chemotherapy (61.5% platinum-taxane).

Conclusions: Before the approval of immunotherapy in China, most patients with resectable early or locally advanced EC underwent radical surgery without preoperative treatment, whereas most patients with advanced EC received platinum-taxane chemotherapy. These findings highlight the need for novel EC treatments before immunotherapy was introduced, and provide a baseline for evaluating the benefits of immunotherapy, now that this treatment is widely used in this setting.