Cancer Biology & Medicine最新文献

Objective: Current clinical staging of pancreatic ductal adenocarcinoma (PDAC) relies predominantly on anatomical resectability, thus limiting its prognostic utility. We developed and validated a pretreatment prognostic grading system incorporating multidimensional parameters.

Methods: Patients with histologically confirmed PDAC undergoing curative-intent pancreatectomy were retrospectively enrolled. Independent prognostic determinants of overall survival (OS) and disease-free survival (DFS), identified through multivariable Cox proportional hazards regression, provided the basis for deriving the Tianjin Prognostic Score and its corresponding risk stratification scheme.

Results: Resectability status, lymph node metastasis indicated by imaging, pretreatment serum CA19-9 levels, and the prognostic nutritional score (PNS) independently predicted both OS and DFS. These parameters were integrated into the Tianjin Prognostic Score for PDAC prognosis stratification. The Tianjin-Grade system, subsequently established according to this score, segregated patients into 4 discrete prognostic cohorts with significantly divergent survival outcomes. This system exhibited significantly greater discriminatory ability for prognosis than conventional serum CA19-9 and resectability criteria. Notably, patients classified as having high risk or extremely high risk derived substantial survival benefits from neoadjuvant chemotherapy (NAC), whereas those with low or intermediate risk demonstrated comparable survival outcomes regardless of NAC administration.

Conclusions: The Tianjin-Grade system provides accurate pretreatment prognosis prediction in patients with PDAC through integration of anatomical and biological parameters, thus serving as a reliable tool for prognostic assessment. This system facilitates the development of personalized preoperative therapeutic strategies.

Over the past 2 decades, remarkable advancements in the screening, diagnosis, and treatment of non-small cell lung cancer (NSCLC) have led to improved patient outcomes. For the treatment of NSCLC with actionable gene mutations, tyrosine kinase inhibitors developed against EGFR, ALK, RET, BRAF, ROS1, NTRK, MET, and KRAS, exhibit substantial antitumor activity and have been incorporated into standard treatment regimens. Additionally, numerous novel therapies, including immunotherapy and antibody-drug conjugate therapy, have been found to benefit patients with NSCLC. This review summarizes current advancements in targeted therapy for NSCLC, according to a systematic search of the PubMed database and synthesis of cutting-edge findings presented at the 2024 American Society of Clinical Oncology Annual Meeting and 2024 World Conference on Lung Cancer.

Immune checkpoint inhibitors have markedly improved outcomes in patients with multiple advanced malignancies. However, their widespread use has markedly increased the incidence of immune-related adverse events (irAEs). irAEs can affect a wide range of organ systems and are characterized by heterogeneous onset, broad toxicity spectra, and complex management requirements, thus ultimately impairing treatment continuation and patient quality of life. This review systematically summarizes the epidemiological features, clinical progression, and current management of irAEs. Existing guidelines largely focus on acute toxicities but have not provided structured strategies for chronic, delayed-onset, or multisystem irAEs. Moreover, clinical practice is hampered by incomplete multidisciplinary collaboration, insufficient training of oncologists, and fragmented treatment pathways, all of which limit the efficacy of irAE management. We propose incorporating irAE management into core oncology training and call for the establishment of comprehensive interdisciplinary frameworks to ensure the standardized long-term use of immunotherapy.

Tumor cells undergo metabolic reprogramming to adapt to rapid proliferation and harsh microenvironments, as evidenced by aerobic glycolysis. Mitochondria serve as key coordinators of this process. Under internal and environmental stress in tumors, mitochondria reprogram metabolism by balancing energy dynamics, redirecting metabolic routes, communicating via metabolites, and preserving the quality of mitochondria, thus supporting tumor cell survival. Traditional Chinese medicine (TCM) has a key role in modulating mitochondrial reprogramming in tumor cells, possibly disrupting metabolic pathways that are necessary for survival and proliferation. However, the underlying molecular signaling and cellular biological mechanisms need to be elucidated. In this review, we focused on the Key functions of mitochondria in adapting to tumor metabolic reprogramming are the focus of this review and recent advances in and regulatory mechanisms of TCM and nano-pharmaceutical formulations in maintaining mitochondrial homeostasis are discussed. These insights may help understand the role of mitochondria in the pathogenesis of metabolic diseases, such as cancer, and identify therapeutic targets.

Neutrophil extracellular traps (NETs) are web-like structures of DNA and proteins that are released by activated neutrophils. While originally identified as antimicrobial defense mechanisms, NETs are now recognized as key modulators of tumor progression. NETs interact with the tumor microenvironment and metabolic pathways in renal cell carcinoma (RCC), which promotes immune evasion and metastasis. This review explores the interplay between NET formation and metabolic reprogramming in RCC, highlighting the implications for immunotherapy resistance and therapeutic targeting. NET-associated signaling, immunometabolism disruption, and current strategies to inhibit NETs in preclinical and clinical settings are discussed. Targeting NETs may represent a promising adjunct in RCC therapy, particularly when integrated with immune checkpoint blockade.

Objective: Osimertinib (OSI) therapy, a cornerstone in treating non-small cell lung cancer (NSCLC), has been severely limited by rapidly developing acquired resistance. Inhibition of bypass activation using a combination strategy holds promise in overcoming this resistance. Biguanides, with excellent anti-tumor effects, have recently attracted much attention for this potential. The current study investigated whether novel biguanide compounds developed by our team could overcome OSI resistance and the underlying mechanisms were explored.

Methods: A comprehensive screening assay using OSI-resistant cells identified the optimal combination of biguanide compounds with OSI. Proteomics, co-immunoprecipitation mass spectrometry, RNA sequencing, and homologous recombination assays were used to elucidate the molecular mechanisms underlying combination therapy. NSCLC tumor tissues, especially OSI-resistant tissues, obtained from our clinic were used to assess the correlations between key proteins and OSI resistance.

Results: SMK-010, a highly potent biguanide compound, effectively overcame OSI resistance in vitro and in vivo. Mechanistical studies showed that BMI1/FGFR1 pathway activation is responsible for OSI resistance. Specifically, silencing BMI1 promoted NEDD4-mediated FGFR1 ubiquitination and proteasomal degradation, whereas SMK-010 treatment induced FGFR1 lysosomal degradation. This reduction in FGFR1 levels impaired homologous recombination, increased DNA damage, and surmounted OSI resistance. Analysis of clinical samples revealed overexpression of BMI1 and FGFR1 in NSCLC tissues and represented potential biomarkers for OSI resistance.

Conclusions: These findings highlight the crucial role of the BMI1/FGFR1 axis in OSI resistance and provide a rational basis for the future clinical application of the biguanide, SMK-010, in combination with OSI.

The occurrence and progression of liver cancer are closely associated with mitochondrial dysfunction. Mitochondria exhibit characteristics, such as decreased oxidative phosphorylation efficiency, abnormal accumulation of reactive oxygen species in liver cancer and promoting tumor proliferation and drug resistance through the Warburg effect, as the core of energy metabolism and apoptosis regulation. Mutations in mitochondrial DNA (mtDNA) and dysregulation of mitochondrial autophagy (mitophagy) further enhance the invasive and metastatic capabilities of liver cancer. Current targeted therapeutic strategies focus on modulating the activity of respiratory chain complexes, regulating calcium homeostasis, repairing mtDNA, and activating mitochondrial apoptotic pathways. Although these approaches have shown therapeutic effects, challenges persist, such as tumor heterogeneity, insufficient drug specificity, and drug resistance. Future research needs to integrate the concept of precision medicine by focusing on breakthroughs in the molecular mechanisms underlying mitochondrial dysfunction, development of targeted delivery systems, optimization of combination therapy regimens, and screening of biomarkers to provide new pathways for individualized treatment. With advances in technology, targeting mitochondrial dysfunction is expected to become an important breakthrough for improving the prognosis of liver cancer.