World journal of clinical oncology最新文献

Background: Breast cancer is a prevalent malignant tumor among women. Despite significant advancements in the development and implementation of various anti-breast cancer therapies, enhancing the efficacy of these drugs while minimizing their toxicity remains a challenge.

Aim: To explore the functional impact of the targeted long chain non-coding RNA (LncRNA) of Chidamide on the activity of natural killer (NK) cells via programmed death-ligand 1 (PD-L1), particularly focusing on the mechanisms by which NK cells influence breast cancer cells.

Methods: This study screened the positive LncRNA molecule Linc01010 through high-throughput sequencing, which can counteract the pharmacological effects of Chidamide. Luciferase localization analysis revealed that the Linc01010 fragment was situated in the proximal exon 4-3 region, identified as its functionally active region. Electrophoretic mobility shift assays and RNA-protein pull-down experiments demonstrated the interaction between Chidamide-induced Linc01010 expression and the target protein mitogen-activated protein kinase kinase 6 (MKK6). Western blotting and quantitative polymerase chain reaction analyses indicated that Chidamide enhanced the expression of the downstream effector PD-L1 by activating the corresponding p38-mitogen-activated protein kinases pathway.

Results: While investigating the effects of the Chidamide-Linc01010-MKK6-PD-L1 axis on the immune cell line NK-92, we observed that tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) secretion was significantly inhibited by this response axis. Furthermore, reducing TRAIL secretion within the tumor microenvironment diminished the death effects in breast cancer cells induced by Chidamide.

Conclusion: Our study provides a robust foundation for improving the effectiveness of current anti-breast cancer medications and for identifying new targets related to drug resistance.

This article comments on the article by Rana and Prajapati published in the recent issue. Cancer remains the most formidable public health problem and contributes to significant mortality worldwide. Tumor heterogeneity, toxicity and acquired resistance limit the efficacy of widely used cancer therapies such as radiotherapy, chemotherapy, gene therapy, and immunotherapy. Regulated cell death maintains cellular homeostasis and is a primary hallmark of cancer. Review by Rana and Prajapati discusses the mechanistic regulation of ferroptosis, autophagy, and mitochondrial dynamics in cancer and highlights the therapeutic possibilities of these regulated cell death pathways for developing more effective and targeted cancer therapies, mainly for aggressive and drug-resistant tumors. Considering the important regulatory role of ferroptosis, autophagy and its dynamic interplay with mitochondrial metabolism in tumor pathogenesis, therapy resistance and metastasis, reshaping of the tumor microenvironment with modulations in autophagy and mitochondrial function could sensitize ferroptosis-resistant tumors to anticancer drugs thereby increase the therapeutic efficacy of existing treatment regimens. Deeper understanding of the crosstalk may lead to the identification of non-invasive biomarkers for detecting ferroptosis-sensitive and resistant tumors, prediction of treatment response and the development of clinically translatable pharmacological strategies to maximize patient benefit while minimizing adverse outcomes.

Background: Thermal ablation (TA), including radiofrequency ablation and microwave ablation, is a commonly used curative treatment for single small hepatocellular carcinoma (sHCC). The relative advantages of TA and surgical resection (SR) in terms of long-term survival remain controversial.

Aim: To compare their long-term efficacy in this patient population.

Methods: This population-based retrospective cohort study included 257 patients who received a first diagnosis of single sHCC and underwent SR or TA from January 2012 to September 2017. The primary endpoints were overall survival (OS) and recurrence-free survival (RFS).

Results: The average follow-up duration was 11.4 years. The 1-, 3-, 5-, and 10-year OS rates were 95.8%, 86.0%, 82.5%, and 74.2% in the SR group vs 97.4%, 85.8%, 78.6%, and 65.6% in the TA group, with the median OS not yet reached. The 1-, 3-, 5-, and 10-year RFS rates were 79.8%, 59.6%, 46.2%, and 24.7% in the SR group vs 83.9%, 61.5%, 47.9%, and 41.2% in the TA group, with median RFS values of 3.95 and 4.63 years, respectively. No significant differences in OS or RFS were observed overall (OS: P = 0.244; RFS: P = 0.180), but in patients ≤ 60 years, TA led to a higher RFS than SR (P = 0.021). Multivariate analysis identified age, tumor differentiation grade, and Child-Pugh classification as independent risk factors for OS, whereas age and differentiation grade were significant risk factors for RFS.

Conclusion: In patients with single sHCC, SR, and TA offered comparable long-term efficacy. However, TA showed superior RFS in patients ≤ 60 years, suggesting that TA may be a reasonable option for younger patients, pending confirmation by prospective studies.

In this article we commented on an article published recently by Jiao et al. This retrospective study confirmed that the triple therapy of transarterial chemoembolization (TACE) combined with programmed death protein ligand 1 inhibitors and molecular targeted therapy can significantly reverse TACE resistance in advanced hepatocellular carcinoma. Compared with TACE alone, the triple therapy reduced the resistance rate from 38.8% to 9.7% and increased the median progression-free survival and median overall survival by 92.3% and 26.8%, respectively. TACE induces tumor antigen release and upregulates programmed death protein ligand 1, activating the effect of immune checkpoint inhibitors while molecular targeted therapy inhibits postembolization vascular regeneration, forming a dynamic synergistic network of embolization-immune activation-vascular inhibition. The maximum tumor diameter, capsule loss, and bilateral distribution were identified as independent predictors. This study provided level I evidence and promoted the transformation of advanced hepatocellular carcinoma treatment from single local intervention to an integrated model of local control-systemic treatment. In the future it will be necessary to analyze the dynamic evolution rules of the tumor microenvironment through cross-omics strategies, further explore biomarkers, optimize treatment sequences, and conduct multicenter prospective trials to verify long-term survival benefits and guide the optimization of individualized sequential treatment.

Current experimental models struggle to simulate the complex process of the transformation from atrophic gastritis to gastric cancer, while gastric organoid technology, especially region-specific modeling, provides a more precise in vitro platform for studying this carcinogenic mechanism. Helicobacter pylori activates carcinogenic signaling pathways through virulence factors, inducing DNA damage, epigenetic dysregulation, and immune microenvironment imbalance, driving inflammation-cancer conversion. Intestinal metaplasia and spasmolytic polypeptide-expressing metaplasia serve as critical precursor lesions, gradually developing into dysplasia and adenocarcinoma under the influence of chronic inflammation and genetic instability through intestinal cell transformation and high trefoil factor 2-expressing cell expansion. The immune suppression, metabolic reprogramming, and matrix remodeling within the tumor microenvironment collaboratively create a pro-cancer ecosystem that accelerates inflammation-carcinogenesis transformation. The gastric organoid model successfully simulates the spatiotemporal dynamics of the carcinogenesis process in atrophic gastritis, and its future integration with single-cell omics, real-time imaging technologies, and artificial intelligence technologies could provide a more precise platform for elucidating molecular mechanisms and screening intervention strategies. These advances position gastric organoids as pivotal tools for clinical translation, enabling personalized risk stratification, early intervention targeting precancerous transitions, and ex vivo prediction of patient-specific therapeutic responses to guide precision management of gastric cancer.

The interaction between the lactate receptor GPR81 (also known as hydroxycarboxylic acid receptor 1, or HCAR1) and Splicing Factor Proline- and Glutamine-Rich protein promotes the tumor cell malignancy. GPR81 nuclear translocation plays an important role in driving cancer progression and could serve as a potential therapeutic target. Yang et al concluded in their study that lactate and its receptor, GPR81, play crucial roles in cancer progression, and are key players in linking the lactate-rich tumor microenvironment to cancer cell behavior. The ability of nuclear GPR81 to directly regulate gene expression, combined with extracellular matrix -mediated mechanical signaling, creates a potentially robust system for the coordinated adaptation and survival of cancer cells. Understanding these interactions could lead to the discovery of new therapeutic targets and improved treatment strategies for cancer.

Background: Rectal cancer management is currently evolving with the advent of different neoadjuvant treatment strategies and organ preservation strategies. A significant proportion of patients could achieve complete clinical response after neoadjuvant treatment, which often translates to pathologic complete response (pCR) as assessed on surgical specimens after curative intent surgery. Endoscopy plays a significant role in assessing treatment response to neoadjuvant therapies.

Aim: To explore the role of endoscopy in predicting subsequent pCR after neoadjuvant treatment in rectal cancer patients.

Methods: An extensive literature review was undertaken to identify the criteria used for assessment of endoscopic response and their ability to predict pCR.

Results: Fifteen studies were identified through literature review. The most commonly used endoscopic criteria for evaluation included the presence of a flat white scar and the absence of nodularity or telangiectasia. Information on the timing of endoscopic assessment in relation to neoadjuvant treatment protocols were also extracted from the studies. In most studies, the diagnostic accuracy for predicting pCR exceeded 0.8. The main limitations identified were the retrospective design of included studies included and a moderate risk of bias.

Conclusion: Endoscopy can be a key prognostic factor in predicting pCR to neoadjuvant treatment in rectal cancer despite significant limitations in currently available data.

Background: Although chronic-phase chronic myeloid leukemia (CP-CML) is treatable and nearly curable in about 50% of patients, accelerated-phase chronic myeloid leukemia (AP-CML) shows concerning drug resistance, while blast crisis chronic myeloid leukemia (BC-CML) is highly lethal. Advances in whole exome sequencing (WES) reveal pan-cancer mutations in BC-CML, supporting mutation-guided therapies beyond Breakpoint cluster region-Abelson. Artificial intelligence (AI) and machine learning (ML) enable genomic stratification and drug repurposing, addressing overlooked actionable mutations.

Aim: To stratify BC-CML into molecular subtypes using WES, ML, and AI for precision drug repurposing.

Methods: Included 123 CML patients (111 CP-CML, 5 AP-CML, 7 BC-CML). WES identified pan-cancer mutations. Variants annotated via Ensembl Variant Effect Predictor and Catalogue of Somatic Mutations in Cancer (COSMIC). ML (principal component analysis, K-means) stratified BC-CML. COSMIC signatures and PanDrugs prioritized drugs. Analysis of variance/Kruskal-Wallis validated differences (P < 0.05).

Results: In this exploratory, hypothesis-generating study of BC-CML patients (n = 7), we detected over 2500 somatic mutations. ML identified three BC-CML clusters: (1) Cluster 1 [breast cancer susceptibility gene 2 (BRCA2), TP53]; (2) Cluster 2 [isocitrate dehydrogenase (IDH) 1/2, ten-eleven translocation 2]; and (3) Cluster 3 [Janus kinase (JAK) 2, colony-stimulating factor 3 receptor], with distinct COSMIC signatures. Therapies: (1) Polyadenosine-diphosphate-ribose polymerase inhibitors (olaparib); (2) IDH inhibitors (ivosidenib); and (3) JAK inhibitors (ruxolitinib). Mutational burden, signatures, and targets varied significantly across clusters, supporting precision stratification.

Conclusion: This WES-AI-ML framework provides mutation-guided therapies for BC-CML, enabling real-time stratification and Food and Drug Administration-approved drug repurposing. While this exploratory study is limited by its small sample size (n = 7), it establishes a methodological framework for precision oncology stratification that warrants validation in larger, multi-center cohorts.

Neurotransmitter-mediated regulation plays a multi-dimensional role in the tumor microenvironment, profoundly influencing key processes such as tumor immune evasion, metabolic reprogramming, and metastasis. However, the upstream regulatory mechanisms linking neural inputs to immune evasion and metabolic reprogramming remain incompletely understood. We systematically summarize current evidence from molecular, cellular, and immunological studies to elucidate how neurotransmitter-dependent mechanisms drive dynamic changes in the tumor microenvironment through the regulation of tumor cells and immune cells, and map the complex interaction networks between the nervous system and tumor progression. We propose a unifying "neuro-metabolic-immune axis" framework that highlights the dual role of neurotransmitters in suppressing anti-tumor immunity and facilitating tumor adaptation. By mapping this axis, we reveal new insights into tumor ecology and identify neural pathways as promising therapeutic targets. Targeting these pathways may enhance immunotherapy and disrupt tumor-supportive metabolism, offering new directions in precision oncology.

Cancer rehabilitation is a critical component of comprehensive cancer care, aiming to improve the quality of life for cancer survivors by addressing physical, psychological, and social challenges following treatment. In India, with rising cancer incidence and a growing survivor population, the need for effective rehabilitation services is more pronounced than ever. However, despite significant progress in cancer treatment, rehabilitation remains an underdeveloped and underutilized area of care in the country. This mini-review explores the current status of cancer rehabilitation in India, highlighting existing gaps in healthcare infrastructure, access, and awareness. It examines the scope of rehabilitation services-including physical therapy, psychosocial support, palliative care, and vocational rehabilitation-and identifies regional variations in service availability. Furthermore, the mini-review outlines challenges faced by healthcare providers, such as a shortage of trained professionals, limited funding, and cultural stigmas surrounding cancer. Future perspectives on cancer rehabilitation in India emphasize the need for policy reforms, integration of rehabilitation into national cancer care programs, and promotion of multidisciplinary care teams. The article concludes with recommendations for expanding cancer rehabilitation services to meet the evolving needs of survivors and to enhance their long-term well-being in India.