Clinical & Translational Oncology最新文献

Cancer remains a leading cause of mortality in developed countries, with advancements in targeted therapies, antibody-drug conjugates (ADCs), and immunotherapy significantly improving patient survival. However, these treatments often result in cutaneous adverse effects (AEs), impacting the skin, mucosa, hair, and nails. This expert consensus statement provides a comprehensive overview of the mechanisms behind these skin toxicities, their clinical manifestations, and the importance of rapid diagnosis and treatment. The spectrum of skin toxicities ranges from mild reactions such as xerosis and pruritus to severe, potentially life-threatening conditions such as Stevens-Johnson syndrome/toxic epidermal necrolysis (SJS/TEN). This statement underlines the need for healthcare professionals to work in multidisciplinary teams, use standardized classification systems such as the Common Terminology Criteria for AEs (CTCAE) v5.0, educate patients on preventive measures, and establish clinical management guidelines to mitigate these AEs. By understanding the pathophysiological mechanisms and implementing effective management strategies such as photoprotection, gentle hygiene, emollients, prophylactic antibiotics, or specific hair and nail care, the quality of life for cancer patients can be significantly improved, ensuring continuity of oncologic treatment and improving overall survival.

Purpose: This study investigates the immunohistochemical expression of SLC48A1 and GLUT-1 in different grades of oral squamous cell carcinoma (OSCC) and explores their potential association with the development of tumor. OSCC is a heterogeneous malignancy characterized by increased glycolysis and glucose oxidation. Heme plays a crucial role in oxidative metabolism and ATP production via mitochondrial oxidative phosphorylation. SLC48A1 (solute carrier family 48 member 1) facilitates GLUT-1 trafficking, enhancing glucose uptake and lactate production, thereby promoting cancer cell migration and invasion. However, the relationship between SLC48A1, GLUT-1, and OSCC remains poorly understood.

Materials and methods: Seventy-two formalin-fixed, paraffin-embedded OSCC tissue samples and ten normal oral mucosa (NOM) were analyzed using immunohistochemistry to assess SLC48A1 and GLUT-1 expression. Staining intensity and distribution were correlated with histopathological grades. Statistical analysis was conducted to evaluate their association with tumor behavior.

Results: GLUT-1 expression showed strong expression in cases of well-differentiated OSCC, supporting its association with tumor. SLC48A1 expression was also seen to be markedly elevated in few cases of poorly differentiated OSCC.

Conclusion: While GLUT-1 expression correlates directly with OSCC, SLC48A1 expression was not seen to be uniformly distributed across the different histological grades. Through this study, it has been proven that both markers hold diagnostic significance and the results of the present study may serve as a future milestone for exploring these markers as potential therapeutic target for disrupting cancer metabolism as well as to correlate with the progression in different grades of OSCC.

Cancer is a disease marked by widespread molecular dysregulation, including alterations in gene expression, signaling pathways, and protein function. Among the critical regulators of protein function are post-translational modifications (PTMs), which fine-tune protein stability, activity, localization, and interactions. At the same time, more and more data has shown that mutations in parts of the splicing machinery, such as SF3B1, SRSF2, U2AF1, and ZRSR2, are common causes of different types of hematologic and solid tumors. Although the transcriptome implications of these mutations have been thoroughly delineated, their subsequent impacts on PTM regulation are still predominantly unexamined. This review seeks to address this deficiency by emphasizing the nascent connections between spliceosome mutations and the alteration of PTM landscapes in cancer. We suggest that modified splicing of PTM-related enzymes and substrates could significantly transform the cancer proteome, providing novel mechanistic insights and therapeutic prospects. We also look into how splicing-driven PTM changes, especially those that affect ubiquitination pathways and other important modification systems, affect the immune landscape of tumors. This gives us new information about how tumors with splicing mutations become more fit by changing the pathways that control the immune system and tumor surveillance.

Background: Brain metastases (BrM) from colorectal cancer (CRC) are rare but carry dismal prognosis. Emerging genomic analyses have identified insulin receptor substrate 2 (IRS2) amplification as a recurrent event in CRC BrM, suggesting a role in brain tropism and metabolic adaptation.

Objective: To systematically evaluate clinical, molecular, and preclinical evidence implicating IRS2 in the pathogenesis and therapeutic targeting of CRC brain metastases.

Methods: We systematically searched PubMed, Embase, Web of Science, and Scopus (inception-Nov 2025) for studies reporting on IRS2 expression, amplification, or perturbation in CRC with emphasis on brain metastases. Human tissue studies, large genomic datasets, and preclinical models (in vivo/in vitro/ex vivo) were included. Data extraction followed PRISMA 2020 guidelines.

Results: Among 312 unique records screened, 6 met inclusion criteria (1 large-scale clinical-genomic cohort, 2 preclinical mechanistic studies, 1 therapeutic evaluation, and 2 grey-literature conference reports). The pivotal Neuro-Oncology 2025 study (Greenberg et al.) demonstrated IRS2 amplification in 7.6% of CRC BrM vs 2.9% of non-brain metastases (p < 0.0001) and confirmed protein overexpression by immunohistochemistry. Functional assays revealed that IRS2 overexpression promotes β-catenin activation, oxidative phosphorylation, and CRC survival in brain-like conditions, while silencing reduces intracranial tumor growth and prolongs survival in mice. Treatment with the dual IRS1/2 degrader NT219 + 5-fluorouracil suppressed CRC BrM growth in vivo.

Conclusion: IRS2 amplification represents a recurrent but non-universal molecular alteration enriched in a subset of colorectal cancer brain metastases, with mechanistic links to β-catenin signaling and mitochondrial metabolism. Preclinical inhibition of IRS2/IRS1-2 demonstrates translational promise, positioning IRS2 as a context-dependent vulnerability and potential therapeutic target in selected CRC brain-metastatic tumors.

Neutrophil extracellular traps (NETs) are web-like structures of decondensed chromatin coated with antimicrobial proteins, released by activated neutrophils as part of innate immunity. Evidence links NETs to cancer-related processes like tumor growth, metastasis, tumor microenvironment. This narrative review synthesizes current evidence on roles of NETs in gynecological cancers. Comprehensive narrative review was conducted to summarize evidence on NETs in gynecological cancers. Literature searches were performed in PubMed, Scopus, Web of Science, Google Scholar using keywords like "neutrophil extracellular traps," "NETs," "ovarian cancer," "endometrial cancer," "cervical cancer," "tumor microenvironment," "metastasis," "biomarkers." Articles published up to August 2025 in English were included. Studies focusing exclusively on other cancers or non-gynecological inflammatory conditions were excluded. Findings were synthesized, highlighting NET formation, functional roles, diagnostic, and therapeutic potentials in gynecological cancers. NETs exhibit a dual role in gynecological cancers, contributing to tumor progression and therapy resistance while also presenting valuable diagnostic and therapeutic opportunities. Their components-NE, MPO, CitH3, cfDNA, and ctDNA are emerging as promising biomarkers for disease monitoring and prognosis. Targeting NETs through DNase therapy, PAD4 inhibition, ROS modulation, or immune regulation holds potential to enhance treatment efficacy and support personalized management of gynecological cancers.

Background: Central nervous system (CNS) metastasis is common in patients with non-small cell lung cancer (NSCLC) and is associated with poor prognosis. Evidence guiding optimal clinical management remains limited, and comprehensive studies on animal models that recapitulate different CNS metastatic patterns are lacking.

Methods: A total of 316 NSCLC patients with CNS metastases were retrospectively enrolled between May 2019 and February 2024. Patients were categorized into four groups: brain metastases only (BM, n = 145), leptomeningeal metastases only (LM, n = 43), concurrent brain and leptomeningeal metastases (BM+LM, n = 62), and brain metastases preceding leptomeningeal metastases (BM-LM, n = 66). Overall survival was analyzed using survival curves. To explore the distinct biological processes underlying BM and LM, mouse models of brain metastasis were established using tail vein, internal carotid artery, and left ventricular injection methods.

Results: Survival analysis demonstrated that patients with LM had significantly shorter overall survival compared with those with BM alone (P < 0.05). Patients with concurrent BM and LM also exhibited poorer overall survival than those in whom BM preceded LM (P < 0.01). In animal experiments, brain metastasis developed in one of five mice following tail vein injection, one of five following internal carotid artery injection, and two of five following left ventricular injection, indicating the highest success rate with the latter approach. None of the animal models successfully reproduced the sequential progression from brain metastasis to leptomeningeal metastasis.

Conclusion: Leptomeningeal involvement in NSCLC is associated with significantly worse survival outcomes compared with brain metastasis alone. Although several injection strategies can generate brain metastasis in mice, current models fail to simulate the transition from brain metastasis to leptomeningeal metastasis, highlighting the need for improved and more representative animal models.

The exponential growth of cancer survivors represents a major healthcare challenge, with more than 23 million people in Europe and 2.2 million in Spain requiring long-term specialized follow-up. Five-year survival has reached 60% in our country, creating a growing population of long-term survivors who need comprehensive care beyond the stage of active oncological treatment. This consensus document between oncology and primary care professionals establishes a care framework based on shared management for the follow-up of cancer survivors. The proposed model is based on the principles of continuity and ongoing communication, equity in access, and efficiency in resource use, recognizing that the needs of these patients go beyond purely medical aspects to encompass physical, psychological, social, and functional dimensions. This proposal defines a dynamic risk stratification that enables the identification of high-risk patients, who will continue to receive preferential hospital follow-up, and low-risk patients, whose care can be led by primary care with the support of other specialists. Specific roles are established for each level of care, along with bidirectional communication pathways and multidisciplinary coordination tools that include shared medical records, agreed protocols, and rapid referral channels.

Pancreatic cancer (PC), predominantly pancreatic ductal adenocarcinoma, remains one of the most lethal malignancies, largely due to late diagnosis and intrinsic resistance to conventional therapies. In recent years, mismatch repair deficiency (dMMR) and microsatellite instability-high (MSI-H) have emerged as clinically actionable biomarkers in a small but distinct subset of PC, accounting for approximately 1-2% of cases. These tumors display unique molecular characteristics, including a high prevalence of wild-type KRAS and TP53, elevated tumor mutational burden, and recurrent kinase fusions, which together confer enhanced immunogenicity and increased sensitivity to immune checkpoint inhibitors (ICIs). In addition to their therapeutic relevance, dMMR/MSI-H status has important diagnostic implications for the identification of Lynch syndrome-associated pancreatic cancers, informing genetic counseling and familial risk assessment. This review summarizes current understanding of the molecular basis of mismatch repair deficiency and microsatellite instability in PC, evaluates available diagnostic approaches such as immunohistochemistry, polymerase chain reaction, and next-generation sequencing, and discusses the prognostic and predictive significance of dMMR/MSI-H status. Emerging clinical evidence supporting the use of ICIs in selected patients across neoadjuvant, adjuvant, and advanced disease settings is also reviewed, along with challenges related to assay discordance, tumor heterogeneity, and immunotherapy resistance. Finally, future directions are highlighted, emphasizing the need for standardized testing algorithms, integration of multi-omics and spatial profiling technologies, and prospective clinical studies to optimize precision treatment strategies for this rare but clinically meaningful subtype of pancreatic cancer.

Background: Pseudomyxoma Peritonei is characterised by peritoneal metastasis from appendiceal mucinous neoplasms (AMN). The PSOGI classification (2016) categorises PMP into acellular mucin (AM), low-grade mucinous carcinoma peritonei (LGMCP), and high-grade mucinous carcinoma peritonei (HGMCP). This study aimed to determine long-term prognosis based on this classification.

Materials and methods: Pathology review from PMP patients with AMNs undergoing cytoreductive surgery and heated intraperitoneal chemotherapy (CRS + HIPEC) with curative intent over a 15-year period (2006-2021) was undertaken. Patients underwent standardised surveillance. Cox proportional hazards regression models, log-rank test, and Kaplan-Meier method were used to assess overall (OS) and disease-free survival (DFS) based on histopathological peritoneal metastasis grade. DFS was only calculated for patients who had a complete cytoreduction.

Results: 290 PMP patients were identified (AM = 34%, LGMCP = 59%, HGMCP = 7%) with median follow-up of 49 months. Median age was 59 years (range: 22-79), M: F of 1:2.5, peritoneal cancer index median of 18 (range: 0-39). Univariate OS hazard ratio (HR) is 2.75 for LGMCP vs AM (95% CI: 1.05 -7.21, p < 0.040) and 14.29 for HGMCP vs AM (95% CI: 3.92- 52.11, p < 0.001). DFS HR = 5.15 for LGMCP (95% CI: 2.19-12.10, p < 0.001) and 4.16 for HGMCP (95% CI: 1.03-16.80, p < 0.045) with an overall peritoneal metastasis p value < 0.001. Multivariate OS analysis showed that peritoneal histology for HGMCP remained a significant predictor of poor prognosis for OS (HR: 5.54, 95% CI: 1.32-23.25, p = 0.019), whilst LGMCP did not demonstrate a significant association (HR: 1.59, 95% CI: 0.59-4.26, p = 0.359).

Discussion: Peritoneal metastasis histopathological grade predicts outcome for patients with PMP from AMN following CRS + HIPEC independent of primary histology.