Ovarian cancer remains a major cause of gynaecological cancer mortality, largely because early disease is frequently asymptomatic and reliable population-based screening remains unavailable. Systemic inflammation is increasingly recognised as an important component of ovarian cancer biology, linking tumour progression, immune dysregulation, angiogenesis, metastasis and treatment resistance. This narrative review critically evaluates blood-based inflammatory biomarkers, including C-reactive protein, interleukin-6, interleukin-8, tumour necrosis factor-α, fibrinogen, neutrophil-to-lymphocyte ratio, platelet-to-lymphocyte ratio, lymphocyte-to-monocyte ratio, systemic immune-inflammation index (SII), systemic inflammation response index (SIRI) and pan-immune-inflammation value (PIV), across early detection, metastatic assessment, treatment decision-making and prognostic stratification. Available evidence indicates that elevated inflammatory indices are consistently associated with advanced disease and adverse outcomes, although substantial heterogeneity exists in biomarker thresholds, populations, timing of measurement and analytical approaches. Recent evidence also suggests that preoperative NLR and SII may contribute to treatment selection, including neoadjuvant chemotherapy, although prognostic independence is not consistently demonstrated. Importantly, inflammatory biomarkers lack sufficient specificity for standalone ovarian cancer screening and should not replace CA-125, HE4, imaging or histopathological assessment. Their greatest clinical potential lies in multimarker models integrating systemic inflammatory, tumour-specific, molecular and clinical variables. Future research should prioritise prospective multicentre validation, standardised thresholds, longitudinal assessment and clinically interpretable prediction models to determine whether inflammatory profiling can advance precision risk stratification and treatment selection in ovarian cancer.
Daniele Ammeti, Debora Curci, Martina Franzin, Marco Rabusin, Melania Eva Zanchetta, Antonella Fabretto
Neuroblastoma (NB) is one of the most challenging paediatric malignancies, accounting for 15% of childhood cancer-related deaths. It is characterised by a high heterogeneity ranging from spontaneous regression to high frequency of metastatic disease at diagnosis. Although current treatment strategies, including chemotherapy, surgery and radiotherapy, have improved outcomes, recurrence often occurs in high-risk NB patients, thus affecting overall survival. In this context, personalised medicine is emerging as a promising approach taking advantage of predictive biomarkers to refine risk stratification and to predict treatment response, together with the development of innovative treatments for high-risk NB. This review summarises the landscape of biomarkers in NB, focusing on genomic, transcriptomic, proteomic, and metabolomic signatures associated with aggressive disease biology, therapeutic resistance, and clinical outcome. We highlight how improved patient stratification could help to identify actionable targets resulting in innovative therapeutic strategies. These include GD2-directed immunotherapy, CAR-T and CAR-NK cell approaches, and pathway-directed agents targeting mainly ALK, and MYCN-associated dependencies. Ultimately, the transition from standardised protocols to a systematic integration of multidimensional biomarker profiles with next-generation therapies promises to transform the clinical management of high-risk NB. Addressing the biological complexity of NB ensures more effective and less toxic interventions, paving the way for personalised therapeutic approaches aimed at preventing relapse in high-risk cases and significantly improving long-term survival.
G. Arrichiello, A. Piccolo, F. Carlino, E. Franzese, A. Ventriglia, M. Annunziata, V. Patanè, M. De Siero, M. D. Bisceglia, M. Orditura
The management of oligometastatic colorectal cancer (OMD-CRC) has undergone a profound evolution, transforming what was once a uniformly fatal diagnosis into a clinical scenario in which long-term survival and even cure are attainable for a carefully selected subset of patients. This review provides a comprehensive synthesis of integrated, multidisciplinary strategies for OMD-CRC, with particular emphasis on hepatic and pulmonary metastases. We examine the biological foundations that differentiate oligometastatic from polymetastatic disease, including molecular subtypes that inform prognosis and therapeutic responsiveness. Local treatment modalities are critically evaluated, ranging from surgical metastasectomy—the standard of care in adequately selected patients—to minimally invasive approaches such as thermal ablation and Stereotactic Body Radiotherapy (SBRT). Recent randomized trials and prospective studies have suggested possible non-inferiority of these alternatives to surgery in selected contexts, thereby broadening the spectrum of curative-intent interventions. Equally pivotal is the integration of systemic therapy. We discuss optimal timing (neoadjuvant, adjuvant, perioperative) and regimen selection for both resectable and initially unresectable disease. The role of conversion therapy, combining intensive chemotherapy with targeted agents guided by molecular determinants such as RAS/BRAF mutational status and tumor sidedness, is highlighted as a cornerstone in expanding surgical eligibility. Looking ahead, emerging technologies—including radiomics and liquid biopsy approaches such as circulating tumor DNA (ctDNA)—hold promise for refining patient selection, detecting minimal residual disease, and further individualizing treatment pathways. The convergence of advanced local therapies, precision-guided systemic regimens, and novel biomarkers delineates the new frontier in optimizing outcomes for patients with OMD-CRC.
Cui Chang, Tang Youming, Lu Ying, Lei Ningning, Guo Chunhui, Wei Dekai, Liang Mei, Wu Qiyuan, Liu Gechen, Wu Fasheng, Chen Jibing
Although radiotherapy (RT) and natural killer (NK) cell-based therapy have shown promising potential in the treatment of non-small cell lung cancer (NSCLC), the therapeutic efficacy and safety of their combination remain to be fully elucidated. In this study, we evaluated the efficacy and safety of combined RT and NK cell therapy and performed preliminary proteomic profiling to characterize its potential effects on the tumor immune microenvironment (TIME), providing new insights and a theoretical and clinical basis for the development of NK cell-based therapeutic strategies for NSCLC. C57BL/6-derived subcutaneous Lewis lung carcinoma models were established to determine the minimal effective dose of both radiotherapy and adoptively transferred natural killer cells. Based on the MED-derived findings, the mice were further randomized into five experimental groups for therapeutic efficacy evaluation: the Control group, the RT group, the NK group, the combination therapy group (RN group), and the repeated combination therapy group (RN2 group). Tumour volume and body weight were monitored longitudinally. Differentially abundant proteins were interrogated by Gene Ontology enrichment and Kyoto Encyclopaedia of Genes and Genomes (KEGG) pathway analyses to systematically describe the synergistic antitumor efficacy of differentially expressed proteins. Compared with RT or NK cell-based immunotherapy as monotherapies, the RN group exhibited markedly enhanced tumor growth inhibition, with no overt treatment-related toxicities observed. Following the second cycle of combined therapy, mice in the RN2 group displayed a more pronounced reduction in tumor growth rate with those in the single-cycle combination cohort; notably, no significant adverse events associated with the combined regimen were detected throughout the entire experimental duration. Proteomic profiling unraveled that RT disrupted the core regulatory networks governing intracellular DNA replication and repair processes in tumor cells in a therapy-specific manner, whereas NK cell immunotherapy potently and selectively activated the classical pathway of the host complement system. Collectively, RT and NK cell therapy demonstrate superior synergistic efficacy and no overt toxicity was observed, with repeated treatments further delaying tumor progression. Mechanistically, proteomics shows that RT disrupts DNA replication/repair networks, whereas NK cell therapy was associated with upregulation of multiple complement components, including those belonging to the classical and lectin pathways, suggesting a potential involvement of these pathways.
NUT carcinoma is a rare and aggressive lung tumor driven by NUTM1 gene rearrangements. It accounts for less than 1% of all lung cancers, with fewer than 100 cases reported worldwide. The disease is often misdiagnosed due to non-specific symptoms and histological overlap with other tumors. This review provides an updated overview of its pathological features, clinical presentation, diagnosis, treatment, and prognosis, aiming to serve as a practical reference for clinicians and pathologists.
