Cancer Biology & Medicine最新文献

Objective: This study aimed to analyze the temporal trends in cancer mortality in China from 2013-2021 and project the future trends through 2030.

Methods: This study was based on the China Causes of Death Surveillance Dataset, which covers 2.37 billion person-years. Age-standardized mortality rates (ASMRs) were calculated using Segi's world standard population and the trends were evaluated via Joinpoint regression. Bayesian age-period-cohort models were used for mortality projections. Contributions of demographic changes (population size and age structure) and risk factors to the mortality burden were quantified using the decomposition analysis.

Results: The combined ASMRs for all cancers decreased annually by 2.3%, driven by significant declines in esophageal (4.8%), stomach (4.5%), and liver cancers (2.7%). In contrast, the pancreatic and prostate cancer ASMRs increased by 2.0% and 3.4% annually, respectively. Urban areas demonstrated a more rapid decline in the combined ASMRs for all cancers [average annual percent change (AAPC) = -3.0% in urban areas vs. -2.0% in rural areas], highlighting persistent disparities. Population aging contributed 20%-50% to death increases between 2013 and 2021. The combined ASMRs for all cancers, like the findings of temporal trend analyses, will continue to decrease and the regional (urban and rural) difference is projected to simulate that of the temporal trend through 2030. In fact, cancer deaths are projected to reach 2.4 million by 2030.

Conclusions: The cancer burden in China is facing the dual challenges of population aging and urban-rural disparities. It is necessary to prioritize rural screening, control risk factors, such as smoking and diet, and integrate more efficacious cancer prevention and control programmes into the policy to reduce mortality in the future.

The tumor immune microenvironment (TIME) represents a complex battlefield where metabolic competition and immune evasion mechanisms converge to drive cancer progression. Amino acids, with their multifaceted biological roles, have emerged as pivotal regulators of tumor cell proliferation and immune cell functionality. The sensing mechanisms by which amino acids within the tumor microenvironment influence cellular growth, survival, and immune function are systematically explored in this review; the latest advances in understanding amino acid metabolism in tumor biology are also reviewed. In addition, the multifaceted roles of key amino acids in shaping the TIME with particular emphasis on tumor immunity and malignant growth were investigated. Finally, emerging therapeutic strategies targeting amino acid metabolism to reprogram the TIME are discussed, highlighting promising approaches, such as CAR-T cell therapy and engineered bacterial interventions. Through this comprehensive analysis, critical insights into future research directions and potential clinical translation of amino acid-targeted interventions are provided.

Organoids are three-dimensional stem cell-derived models that offer a more physiologically relevant representation of tumor biology compared to traditional two-dimensional cell cultures or animal models. Organoids preserve the complex tissue architecture and cellular diversity of human cancers, enabling more accurate predictions of tumor growth, metastasis, and drug responses. Integration with microfluidic platforms, such as organ-on-a-chip systems, further enhances the ability to model tumor-environment interactions in real-time. Organoids facilitate in-depth exploration of tumor heterogeneity, molecular mechanisms, and the development of personalized treatment strategies when coupled with multi-omics technologies. Organoids provide a platform for investigating tumor-immune cell interactions, which aid in the design and testing of immune-based therapies and vaccines. Taken together, these features position organoids as a transformative tool in advancing cancer research and precision medicine.

Breast cancer (BC) has the highest prevalence among cancers specific to women, and its incidence rates are increasing in many countries. Subtypes of BC, including HER2-positive or triple-negative BC, exhibit differing treatment responses; consequently, demand for personalized therapy is increasing, and relevant precision medicine strategies are under development. Aerobic glycolysis in cancer cells can lead to excessive lactate production, which in turn promotes lactylation and influences tumor cell behavior. Epigenetic alterations and metabolic reprogramming are prominent characteristics of tumors. Because lactate and lactylation are important in cancer, further investigation of the mechanisms underlying lactate metabolism and lactylation, and the development of therapeutic strategies targeting these processes, are topics of increasing interest. This review describes current research on lactate metabolism and lactylation in BC, thus offering new perspectives for advancing treatment and management toward more precise and personalized approaches that will ultimately increase BC survival rates and patient quality of life.

Objective: Gemcitabine combined with nab-paclitaxel therapy (GnP) represents first-line chemotherapy for advanced pancreatic ductal adenocarcinoma (PDAC). However, the efficacy of GnP is diminished due to chemotherapeutic resistance induced by the tumor microenvironment (TME), the underlying mechanisms of which remain poorly understood.

Methods: Clinical data from patients with PDAC who underwent GnP therapy were collected and neutrophil infiltration in tumor tissues was assessed. PDAC cell lines and a mouse model of PDAC were utilized to determine the mechanisms underlying GnP resistance and to focus on tumor-associated neutrophils and neutrophil extracellular traps (NETs).

Results: GnP therapy recruited neutrophils to the TME, which resulted in the formation of NETs that contributed to therapeutic resistance in the PDAC murine model. The NET inhibitor, PAD4, enhanced the efficacy of GnP by suppressing tumor growth. Furthermore, GnP significantly upregulated CXCL8 secretion in GnP-resistant MIA PaCa-2 cells, which was mediated by increased expression of GPRC5A in PDAC cells. Screening of classic NET-derived molecules identified cell-free DNA (cfDNA) as a pleiotropic factor that promoted tumor cell proliferation and migration and thereby contributed to chemotherapeutic resistance. In vivo experiments revealed that the combination of GnP with siGPRC5A or DNase was more effective in reducing tumor growth and prolonging survival in PDAC-bearing mice than either treatment alone.

Conclusions: The GPRC5A-CXCL8-NET-cfDNA axis has a critical role in the development of therapeutic resistance to GnP in PDAC. Targeting this axis may represent a promising strategy for overcoming GnP resistance and thereby enhancing the efficacy of chemotherapy in PDAC.

Objective: Hyper-progression recurrence (HPR) after hepatectomy is a specific recurrence pattern associated with extremely poor prognosis in patients with hepatocellular carcinoma (HCC). This study was aimed at investigating the probable risk factors and establishing comprehensive models for formulating clinical strategies.

Methods: Overall, 16,158 patients with HCC from 8 hospitals were screened, among whom 3,125 patients who underwent R0 resection were included, and divided into development (n = 2,113) and validation (n = 1,012) cohorts. A comprehensive study of HPR predictive models and biological features was conducted.

Results: Among the 3,125 enrolled patients, 506 (16.19%) developed HPR. The influence of HPR on extremely poor prognosis was reflected by recurrence features, adverse effects on systemic and liver function, and limited therapeutic options. Nine variables closely associated with HPR were identified, and incorporated into nomogram and conditional inference tree models, which successfully achieved pre- and post-operative HPR risk stratification and facilitated clinical decision-making. Multi-dimensional verification also confirmed the predictive accuracy of model combinations and their reliability in clinical applications. Furthermore, biological analyses revealed that HCCs with HPR exhibited hyperactive biological processes, inactive metabolism, and immune exhaustion features, together with high MYCN/HMGA2 co-expression, thereby enhancing understanding of the molecular events leading to HPR and providing valuable knowledge for HPR management.

Conclusions: HPR after hepatectomy is associated with extremely poor prognosis and requires substantial attention. We constructed comprehensive predictive models and propose a clinical strategy for guiding HPR prevention and management.

Prostate cancer (PCa) is a leading cause of cancer-related mortality among men. Radiotherapy is the cornerstone of PCa treatment. However, a major limitation of radiotherapy is the development of resistance, which compromises treatment efficacy. Reactive oxygen species (ROS), which are generated by radiation, have a dual role in PCa by inducing DNA damage and apoptosis, while also promoting tumor progression and radioresistance. Elevated ROS levels enhance metabolic reprogramming, activate oncogenic pathways, and influence the tumor microenvironment by modulating immune responses and promoting the epithelial-mesenchymal transition (EMT). Key molecular mechanisms, including the Nrf2/Keap1 signaling axis, Bcl-2 mutations, and Speckle-type POZ protein alterations, contribute to radioresistance by enhancing antioxidant defenses and DNA repair capacity. Additionally, the interplay between hypoxia, androgen receptor variants (AR-Vs), and ferroptosis regulators further influence radiotherapy outcomes. Understanding these resistance mechanisms is crucial for developing targeted strategies to enhance radiosensitivity and improve therapeutic outcomes in PCa patients.