Oncology Research最新文献

The tumor microenvironment (TME) is a complex network composed of non-tumor cells, extracellular matrix, blood vessels, and various molecular signals that surround and profoundly influence tumor progression. As one of the key immune effector cells within the TME, mast cells (MCs) exhibit functional complexity, and their specific roles remain widely debated. Depending on the cancer type, spatial distribution, and interactions with other TME components, MCs can demonstrate dual regulatory capabilities-either promoting or inhibiting tumor growth. This characteristic has made them an important focus in current tumor immunology research. This review aims to systematically review the current understanding of MCs in the TME, with emphasis on their characteristics and functional differences across various tumor types, pathological status, and species. In recent years, advances in the understanding of MC markers, activation mechanisms, and biological functions have made targeting specific MC subsets an emerging therapeutic strategy. By comprehensively examining the origin, activation mechanisms, cellular interactions, and therapeutic regulation of MCs, this review provides new perspectives and a basis for future directions in tumor research and treatment.

Background: Adult medulloblastoma (MB) represents less than 1% of central nervous system malignancies, lacking standardized therapeutic approaches due to its rarity. This retrospective single-center analysis aimed to assess survival outcomes and treatment-associated toxicities in adult MB patients managed with pediatric-derived protocols.

Methods: Eighteen patients (≥18 years) with MB treated at Fondazione Policlinico Universitario Agostino Gemelli Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS) (January 1997-January 2024) were analyzed. All received craniospinal radiotherapy with posterior fossa boost, followed by adjuvant chemotherapy utilizing pediatric regimens (PNET3, PNET4, PNET5, or high-risk protocols incorporating high-dose chemotherapy with autologous stem cell rescue). Primary outcomes included overall survival (OS) and progression-free survival (PFS). Secondary analyses focused on comprehensive toxicity assessment.

Results: The cohort included 11 males and 7 females (median age: 23 years). Metastatic disease was present in 6 patients (33%) at diagnosis. Histopathological distribution showed classic MB (55.5%), desmoplastic/nodular (39%), and large cell/anaplastic variants (5.5%). Molecular subgrouping (available in 6 patients) identified SHH subgroup in four cases and WNT subgroup in two. Three-year and five-year overall survival rates reached 94.5% and 88.8%, respectively. Treatment-related adverse events included grade 3-4 hematologic toxicities, clinically significant weight loss, and grade ≥3 neurological and ototoxic complications. These toxicities necessitated treatment modifications including dose adjustments, cycle delays, and occasional early discontinuation.

Conclusions: Adult MB patients treated with pediatric-adapted protocols demonstrated excellent long-term survival outcomes, comparable to or surpassing historical data. Despite frequent toxicity requiring treatment modifications, these regimens proved feasible with acceptable risk-benefit profiles. These results support implementing modified pediatric protocols for adult MB management. Future multicenter investigations with larger cohorts are essential for refining risk stratification, optimizing treatment intensity, and evaluating long-term outcomes in this rare malignancy.

Objective: Patients with stage III non-small cell lung cancer (NSCLC) present with a heterogeneous disease profile and often require multifaceted treatment strategies. This research aimed to investigate the demographic features, therapeutic patterns, and survival outcomes of such patients in Vietnam.

Methods: A retrospective descriptive study was conducted on 731 patients diagnosed with stage III NSCLC American Joint Committee on Cancer (AJCC) 8th edition, at Nghe An Oncology Hospital from January 2018 to August 2024. Descriptive statistics summarized baseline and treatment characteristics. We calculated progression-free survival (PFS) and overall survival (OS) through the Kaplan-Meier approach and compared survival curves with the log-rank test. Prognostic variables were assessed using Cox regression analysis.

Results: Patients had a median age of 64 years, and the majority (84%) were male. Disease stages IIIA, IIIB, and IIIC accounted for 26.0%, 49.9%, and 24.1% of cases, respectively. Adenocarcinoma (60.7%) was the most common histological subtype. Initial treatments included surgery (8.5%), concurrent chemoradiotherapy (38.6%), sequential chemoradiotherapy (2.2%), radiotherapy alone (1.4%), systemic therapy (37.3%), and palliative care (12.0%). From 2018 to 2024, the use of systemic therapy declined (88.5% to 21.7%), while concurrent chemoradiotherapy rose significantly (1.1% to 51.5%). Median progression-free survival (mPFS) and median overall survival (mOS) were 8.9 months and 20.5 months, respectively. Patients with stage IIIA had significantly better outcomes (mPFS: 12.6 months; mOS: 32.4 months; p < 0.001). Surgical treatment yielded the longest survival (mPFS: 13.5 months; mOS: 42.8 months). Favorable prognostic factors included adenocarcinoma subtype, presence of driver mutations, stage IIIA, and good performance status.

Conclusion: For stage III NSCLC, concurrent chemoradiotherapy is still considered the standard treatment, whereas surgery can provide the highest survival advantage in carefully selected cases. Histology, molecular profile, and disease stage are key prognostic indicators.

Background: Current chemotherapy treatments, including the TIP (Taxol, Ifosfamide, Cisplatin) regimen, have shown limited effects but strong side effects in advanced Penile squamous cell carcinoma (PSCC) patients. Trophoblast cell-surface antigen-2 (TROP-2) is a novel target for antibody-drug conjugate (ADC) drugs and has been proven to be effective in several human cancers. This study aimed to explore the biological function and potential of the ADC target in PSCC cells.

Methods: A total of 196 PSCC tumor tissue specimens and clinicopathological data were collected. TROP-2 expression was detected by IHC, and the correlation between TROP-2 expression and the clinicopathological data of patients was analysed through statistical methods. Then, a series of in vivo and in vitro experiments were conducted to investigate the mechanism by which TROP-2 promotes PSCC cell proliferation. Additionally, the efficacy of TROP-2-targeted ADC and cisplatin was tested in PSCC cell lines and animal models.

Results: Immunohistochemistry (IHC) revealed that TROP-2 was highly expressed in 60.2% of tumor specimens, and statistical analysis revealed that high TROP-2 expression correlated with advanced pT and pN stages and extranodal extension (ENE), as well as poor prognosis. Knockdown of TROP-2 inhibited the proliferation of PSCC cells both in vivo and in vitro, and this inhibitory effect was later proven to be mediated by protein kinase B (AKT), which is involved in the protein kinase C alpha (PKCα) signalling pathway. Furthermore, compared with cisplatin, TROP-2 targeted ADC could achieve an equivalent inhibitory effect on the proliferation of PSCC both in vivo and in vitro.

Conclusion: TROP-2 promoted PSCC cell proliferation via AKT/PKCα-dependent pathway, and TROP-2-targeted ADC-drug has a gratifying inhibitory effect on PSCC proliferation both in vivo and in vitro.

Objective: The plastic role of regulatory factor X1 (RFX1) in colon cancer progression and its impact on the tumor microenvironment remain poorly understood. The study aimed to clarify the molecular and clinical role of RFX1 in colon cancer.

Methods: We classified colon cancers into subgroups with high and low RFX1 expression and characterized their immune profiles, mutational profiles, cancer immunotherapy and drug sensitivity. By combining RFX1 expression with persistent tumor mutational burden, we proposed a novel nomogram clinical prediction model and validated its predictive performance, and the correlation between high expression and poor prognosis.

Results: Compared to tumor mutational burden (TMB), persistent tumor mutational burden (pTMB) is an independent predictor of prognosis in patients with colon cancer. The predictive efficacy of the combination of RFX1 expression and pTMB was superior to and sensitive than the combination of RFX1 expression with TMB. Among them, patients in the RFX1^high/pTMB^high subgroup had the worst quality of survival and prognosis, whereas those in the RFX1^low/pTMB^low subgroup had a relatively better prognosis (p < 0.0001). Univariate Cox regression revealed a significant association between high RFX1 expression and increased risk in colon cancer patients (Hazard Ratio [HR] = 1.58, 95% Confidence Interval [CI]: 1.10-2.25, p = 0.012), which remained independently predictive in multivariate analysis after covariate adjustment (HR = 1.52, 95% CI: 1.04-2.22, p = 0.031).

Conclusion: A nomogram model based on RFX1 combined with pTMB provides an alternative approach for the diagnosis and treatment of colon cancer.

[This retracts the article DOI: 10.3727/096504016X14732772150262.].

[This retracts the article DOI: 10.3727/096504016X14743337535446.].

Objective: Testicular germ cell tumors (TGCTs) represent the most common malignancy among young men aged 20-40 years. Transglutaminase 7 (TG7), encoded by TGM7, is a poorly characterized enzyme whose function in TGCT remains unknown. This study aimed to assess TG7 expression in clinical specimens and investigate its functional role in a testicular germ cell tumor cell line (NT2/D1).

Methods: TG7 protein expression was evaluated in clinical testicular tissue samples via immunohistochemistry (IHC) and immunofluorescence (IF). Functional analysis was conducted in the NT2/D1 human testicular cancer cell line using Dicer-substrate small interfering RNAs (DsiRNAs) targeting TG7. Gene knockdown efficiency was confirmed by reverse transcription quantitative PCR (qRT-PCR), and protein suppression was validated by immunofluorescence. Cell viability was assessed using the MTT assay. The expression of inflammation and apoptosis-related genes was quantified via qRT-PCR.

Results: TG7 expression was significantly elevated in testicular germ cell tumor tissues, showing approximately a 4.5-fold increase compared to normal testis, with strong localization in tumor nests and stromal compartments. In NT2/D1 cells, TG7 silencing using 20 nM DsiRNA3 led to a dose-dependent reduction in cell viability, with up to 48% inhibition observed at 200 nM (MTT assay, ****p < 0.0001). qRT-PCR analysis revealed significant upregulation of IL6 (3.2-fold), TNFα (2.8-fold), and CASP3 (2.5-fold) mRNA levels following TG7 knockdown (p < 0.0001), while p53 expression remained unchanged. These findings support TG7's role in modulating tumor cell survival, inflammation, and apoptosis via p53-independent pathways.

Conclusion: Collectively, TG7 is significantly overexpressed in TGCT tissues and supports tumor cell viability in vitro. This study establishes TG7 as a novel biomarker and therapeutic target in testicular cancer, laying the groundwork for future studies on TG7-targeted interventions.

Background: Chimeric antigen receptor T (CAR-T) cell therapies have demonstrated significant clinical efficacy in hematological malignancies. However, their application to solid tumors remains substantially limited by multiple challenges, including the risk of off-target effects. Hence, optimizing CAR-T cells for stronger antigen binding is essential.

Methods: In this study, we employed a classical anti-human endothelial growth factor receptor 2 (HER2) single-chain variable fragment (scFv) derived from trastuzumab, alongside an anti-HER2-13 scFv identified from a combinatorial cellular CAR library, for the construction of a third-generation CAR-T cell. Meanwhile, the phenotypes and both in vitro and in vivo functions of CAR-T cells transduced with the two scFvs via PiggyBac transposon-mediated gene transfer were compared.

Results: The optimal ratio between the PiggyBac HER2-CAR-puro transposon and the Super PiggyBac transposase plasmid differed during the construction of the two HER2-targeted CAR-T cell types. The expansion abilities, CD3⁺CAR⁺ population, CD4⁺CAR⁺/CD8⁺CAR⁺ proportions, and memory and exhaustion markers between the two CAR-T groups were similar after using the optimized proportion of plasmid. Both CAR-T cell types exhibited significant antitumor activity, with the anti-HER2-13 CAR-T cells demonstrating superior target specificity. Therapeutic effects were observed with both CAR-T cells and trastuzumab in the MDA-MB-231^HER2+ breast tumor xenograft model, with anti-HER2-13 CAR-T cells demonstrating slightly enhanced efficacy and no evident off-target toxicity.

Conclusion: These results highlight the potential of anti-HER2-13 CAR-T cells to serve as a safer and more efficacious alternative in HER2-targeted therapy.

The ever-expanding development of tissue-agnostic therapies which target malignancies based on specific mutations rather than tissue origin have transformed the landscape of oncology. The purpose of this review is to explore the impact, safety, and challenges of tissue-agnostic therapies including pembrolizumab, dostarlimab, larotrectinib, entrectinib, repotrectinib, dabrafenib plus trametinib, selpercatinib, and trastuzumab deruxtecan. As the therapeutic arsenal continues to grow, it is crucial to understand how these therapies truly benefit patients and to address the barriers that stand in the way of making them more widely available. Although these therapies have shown effectiveness across multiple cancer types, substantial challenges persist, including overcoming the burden of intratumoral heterogeneity and resistance mechanisms that reduce therapeutic efficacy. We discuss emergence of pan-histological biomarkers, such as neoantigen burden, current updates on trials as well as trial outlining strategies to refining patient selection, while also supporting broader access to biomarker testing. Collectively, these insights underscore the transformative role of tissue-agnostic therapies in precision oncology while emphasizing the ongoing need for research to optimize their application and overcome current barriers.