World journal of clinical oncology最新文献

Digestive tract tumors represent a substantial global public health challenge, accounting for elevated morbidity and mortality rates. Perineural invasion (PNI), the spread of tumor cells along nerve fibers, has emerged as a key driver of aggressiveness and a poor prognosis. This study systematically reviews the complex, underexplored interplay between PNI and antitumor immunity in gastrointestinal cancers. By analyzing immune-related components (the programmed cell death protein 1/programmed death ligand 1 axis, T cell subsets, tumor-associated macrophages, and other immune checkpoints), it reveals PNI disrupts immune balance: It suppresses T-cell activity via programmed death ligand 1/programmed cell death protein 1 binding, skews T-cell differentiation to reduce antitumor efficacy and boost immunosuppression, and polarizes macrophages to aid tumor progression. These findings provide novel insights into how PNI reshapes the tumor immune microenvironment and promotes metastatic behavior, establishing a framework for prioritizing immunotherapeutic targets to inform precision treatment strategies.

Malignant tumors represent a major threat to human life and health, posing persistent challenges in medical research. While chimeric antigen receptor T (CAR-T) cell therapy has demonstrated breakthrough efficacy in hematological malignancies such as leukemia and lymphoma, its application in solid tumors, including hepatocellular carcinoma, lung cancer, and pancreatic cancer, remains constrained by multiple bottlenecks. These limitations encompass the immunosuppressive tumor microenvironment, insufficient in vivo persistence of CAR-T cells, long-term treatment-induced exhaustion, and off-target toxicity. The interleukin (IL)-2 family cytokines, IL-2, IL-4, IL-7, IL-9, IL-15, and IL-21, also known as gamma chain (γc) cytokines, share the γc (CD132)-Janus kinase 1/3-signal transducer and activator of transcription signaling axis. These cytokines precisely regulate the survival, proliferation, and functional differentiation of immune cells, including T cells and natural killer cells. In CAR-T immunotherapy, γc cytokines are applied in four core scenarios: Facilitating efficient in vitro CAR-T cell expansion to meet therapeutic dosing requirements; enhancing in vivo persistence to extend the therapeutic window; reinforcing effector functions to counteract tumor microenvironment-mediated suppression; and enabling precise cytokine release to mitigate toxicity risks. Technological strategies have evolved from early recombinant protein administration (in vitro and in vivo) to second-generation "armored" CAR-T cells engineered for autocrine cytokine secretion and further to third-generation programmable cytokine circuits using synthetic biology for spatiotemporal control. This review systematically summarizes the mechanistic roles, research progress, and technological evolution of γc cytokines in optimizing CAR-T cell function. It critically analyzes the advantages and limitations of different application strategies and explores their potential to overcome solid tumor treatment bottlenecks while improving CAR-T therapy safety and efficacy. These insights aim to inform basic research and clinical translation in this field.

Background: Despite widespread mammographic screening, a substantial proportion of breast cancers are still diagnosed as palpable lesions, frequently self-detected by the patient. Prior studies have investigated palpability as a prognostic factor, but few have incorporated contemporary staging systems or focused on clinically homogeneous, screening-eligible populations. In high-resource settings with equal access to screening, it remains unclear whether palpability reflects intrinsic tumor aggressiveness rather than delayed detection. This study evaluates whether palpable tumors exhibit distinct clinicopathological characteristics and worse outcomes in a screening-eligible population, hypothesizing that palpability may reflect aggressive tumor biology and potentially influence prognosis even when screening programs are accessible.

Aim: To compare clinicopathological features and survival outcomes of palpable vs non-palpable breast cancers in a screened population.

Methods: We retrospectively analyzed 2110 women with clinically node-negative, localized breast cancer treated surgically between 2004 and 2024. Palpability at diagnosis was used to classify tumors as palpable (n = 1234) or non-palpable (n = 876). Endpoints included tumor size, grade, subtype, Ki-67 index, nodal status, overall survival, and breast cancer-specific survival. Statistical analyses included χ ² and t-tests and Kaplan-Meier estimates, with significance set at P < 0.05.

Results: Palpable tumors were significantly larger (17.5 mm ± 8.6 vs 11.0 ± 6.7 mm, P < 0.001), more often high-grade (G3: 33% vs 16.3%, P < 0.001), and more frequently of luminal B or triple-negative subtype (37.1% vs 20.6%, P < 0.001). Ki-67 proliferation index was markedly higher in palpable tumors (24.7% ± 11.9% vs 15.1% ± 9.4%, P < 0.001). Sentinel lymph node positivity was increased (27.6% vs 16.7%, P < 0.001). While 10-year overall survival was similar (92% palpable vs 95% non-palpable, P = 0.56), breast cancer-specific survival showed a trend toward worse survival in palpable cases (96% vs 99%, P = 0.1).

Conclusion: Palpable tumors display faster growth kinetics and aggressive features, potentially shortening the preclinical window. Palpability may indicate biologically aggressive disease, warranting individualized management despite access to routine screening.

This article of discusses blast crisis chronic myeloid leukemia (CML), which is the most aggressive CML phase marked by rapid progression, substantial mutational complexity, and resistance to standard tyrosine kinase therapies. The methodology combines whole exome sequencing and machine learning to identify the molecular subtypes of blast crisis-CML and repurpose existing Food and Drug Administration-approved drugs on the basis of the Catalogue of Somatic Mutations in Cancer mutational patterns. In a pilot cohort (n = 7), three exploratory genomic clusters were identified: Breast cancer gene 2/tumor protein p53; isocitrate dehydrogenases (IDH) 1 and IDH 2 ten eleven translocation 2; and Janus kinase (JAK) 2/colony stimulating factor 3 receptor. The results present an opportunity to evaluate poly(ADP ribose) polymerase inhibitors (breast cancer gene 2/tumor protein p53), IDH inhibitors (IDH1/2 or ten eleven translocation 2), and JAK inhibitors (JAK2 or colony stimulating factor 3 receptor) as actionable therapeutics. Moreover, this e article presents as a strategic framework for mutation-targeted therapy targeting treatment-resistant leukemias, highlighting the potential of artificial intelligence-driven molecular stratification and uncovering clinically relevant therapeutic options for malignancies. However, limitations should be acknowledged, such as the limited cohort size and the necessity for validation in larger multicenter investigations. Prospective registries and trial enrollment should test signature-defined micro-cohorts with versioned and auditable reporting. These mappings are designed to provide hypotheses and depend on independent functional validation, prioritizing safety in combination methods with tyrosine kinase inhibitors, and allows for practical implementation in rapid turnaround environments.

Background: Hepatocellular carcinoma (HCC) is a leading cause of cancer-related mortality, particularly in Egypt, where hepatitis C virus (HCV) prevalence is high. T cell exhaustion markers such as programmed death 1 (PD-1), T cell immunoglobulin and ITIM domain, and T cell immunoglobulin and mucin domain-containing protein 3 (TIM-3) play a crucial role in HCC immune evasion; however, their expression patterns in Egyptian patients remain underexplored.

Aim: To characterize the expression of PD-1, T cell immunoglobulin and ITIM domain, and TIM-3 on CD4+ and CD8+ T cells across HCV-related liver disease stages and to determine their association with disease severity and survival in an Egyptian cohort.

Methods: This prospective case-control study included 200 Egyptian participants: 50 with HCV-related HCC, 50 with HCV-related cirrhosis, 50 with chronic HCV infection, and 50 healthy controls (HCV-negative by polymerase chain reaction). Flow cytometry quantified immune exhaustion markers, and clinical data were analyzed using multivariate and survival modeling frameworks, adjusting for key confounders.

Results: HCC patients showed significantly higher expression of all T-cell exhaustion markers than other groups (P < 0.001). Alpha-fetoprotein (AFP) levels were markedly elevated in HCC (median 13210 ng/mL, P < 0.001). Marker expression showed strong positive correlations with Child-Pugh class, AFP, and Barcelona Clinic Liver Cancer stage, and a negative correlation with model for end-stage liver disease score (all P < 0.001). Non-survivors (34%) had higher marker expression and AFP levels than survivors (P < 0.001). Receiver operating characteristic analysis demonstrated excellent mortality prediction for CD4/PD-1 [area under the curve (AUC) = 0.92] and AFP (AUC = 0.89), while combining AFP with CD8/TIM-3 achieved the best accuracy (AUC = 0.95). Cox regression identified high CD8/TIM-3 expression and Barcelona Clinic Liver Cancer stage D as independent mortality predictors, and CD4/PD-1 partially mediated AFP's effect on mortality (β = 0.45, P < 0.001).

Conclusion: Elevated T cell exhaustion markers were linked to advanced disease and poor survival in Egyptian patients with HCV-related HCC. Machine learning and mediation analyses identified CD4/PD-1 and CD8/TIM-3 as independent prognostic biomarkers, reinforcing their potential as therapeutic targets. These findings provide novel insights from a high-HCV-prevalence setting, supporting the integration of immune exhaustion profiling into risk stratification for HCC.

This commentary discusses the groundbreaking study by Ebrahim et al on the role of claudin-6 (CLDN6) in high-grade endometrial carcinoma, addressing a significant gap in current knowledge. Their research reveals that overexpression of CLDN6 is linked to unfavorable pathological features. Moreover, multivariate analysis establishes CLDN6 as an independent predictor of disease-free survival, with a hazard ratio of 68.98. These results highlight the promise of CLDN6 in improving risk stratification and as a potential therapeutic target, especially with the development of CLDN6-directed antibody-drug conjugates. To advance CLDN6 towards clinical application, further validation in prospective patient cohorts and studies exploring its interactions with other molecular pathways are essential.

Chimeric antigen receptor T cell therapy (CAR-T) has revolutionized the treatment of hematologic malignancies, but its success in solid tumors, particularly those of the digestive system, remains limited. Tumors of the gastrointestinal system, including gastric, colorectal, esophageal, hepatic, and pancreatic malignancies, represent a significant global health burden with high morbidity and mortality. Recent advances in antigen selection, chimeric antigen receptor design, delivery techniques, and combinatorial approaches have sparked renewed interest in CAR-T immunotherapy for these cancers. This article discusses recent progress in CAR-T development across the major digestive system tumors, outlines tumor-specific targets and clinical trials, highlights prevailing challenges and potential solutions, and proposes strategic directions for the next generation of CAR-T therapies in solid tumors.

Small bowel lymphatic malformations are rare benign tumors of the lymphatic system, accounting for < 1% of intra-abdominal lymphatic malformations. They pose diagnostic challenges due to nonspecific presentations and are often misdiagnosed. To analyze clinical features, management, and outcomes of small bowel lymphatic malformations in adults through a case report and scoping review. A 47-year-old female with chronic abdominal pain underwent laparoscopic resection of an ileal lymphatic malformation. A Preferred Reporting Items for Systematic Reviews and Meta-Analyses extension for scoping reviews-guided scoping review of 97 adult cases (1991-2024) was conducted, extracting demographics, diagnostics, management, and outcomes. The cohort included 41 case reports and 2 case series (46% female, mean age 45.6 years), most commonly presenting with abdominal pain (74%), gastrointestinal bleeding (39%), or asymptomatic masses (9%). Lesions were predominantly in the jejunal mesentery (52%), with a mean size of 9.2 cm. Computed tomography identified lesions in 87% of cases, showing multiloculated cystic masses (78%). Surgical resection was the primary treatment (91%), with segmental bowel resection most frequent (65%). Complications occurred in 24% (infections: 13%), and recurrence in 11% (linked to incomplete resection). Complete excision achieved symptom resolution in 93%. Small bowel lymphatic malformations are rare but may cause significant morbidity. Surgical resection is curative, with laparoscopy emerging as a viable approach. Preoperative diagnosis remains challenging; heightened imaging awareness and complete excision are critical to prevent recurrence.

Background: Breast cancer surgery often leads to acute postoperative pain that affects early recovery. Electroacupuncture (EA) is a potential adjunct to analgesics such as flurbiprofen axetil (FA), but evidence on its perioperative benefits remains limited.

Aim: To investigate the effects of EA combined with FA on postoperative pain and early functional recovery after breast cancer surgery.

Methods: A total of 130 patients with breast cancer were randomly divided into EA group (n = 65) and control group (n = 65). Patients received EA or sham acupuncture from 30 minutes before anesthesia induction until surgery end. Both groups received FA postoperatively. We observed the occurrence of postoperative pain (incidence of moderate-to-severe pain during movement and at rest, Visual Analog Scale score) at 24 hours, 48 hours, 72 hours postoperatively, the score of basic activities of daily living (BADL) at 24 hours postoperatively and complications after surgery in both groups of patients.

Results: Compared with the control group, the EA group lowered the incidence of moderate-to-severe movement-evoked pain at 24 hours postoperatively (P < 0.05), and reduced Visual Analog Scale scores during movement and at rest 24 hours after surgery (P < 0.01). The scores of BADL for grooming, dressing, toileting, and transferring (moving in and out of a bed or chair) were significantly better in the EA group than in the control group 24 hours after surgery (P < 0.05), the total BADL score was significantly higher (P < 0.01). The incidence of postoperative complications (nausea, vomiting, loss of appetite) was significantly reduced in the EA group (P < 0.05).

Conclusion: EA combined with flurbiprofen FA can reduce the occurrence of postoperative pain and complications, improve early postoperative functional recovery after breast cancer surgery.

Macroautophagy (hereafter referred to as autophagy) is a lysosomal degradation pathway that clears and recycles cytosolic oncogenic factors, excess lipids, and damaged mitochondria, thereby potentially preventing cancer initiation. Recent studies using in vitro and animal cancer models, as well as clinical investigations in cancer patients, indicate that intermittent fasting exerts beneficial effects, particularly by reducing chemotherapy-related toxicity and slowing tumor growth through multiple mechanisms, including metabolic reprogramming, immune modulation, attenuation of inflammation, and upregulation of autophagy, among others. In this review, we briefly discuss the molecular mechanisms underlying intermittent fasting-mediated cancer prevention and therapy, including the role of autophagy and related clinical implications, highlighting its potential as a valuable adjunct to chemotherapy that warrants further large-scale investigations.