Abstract: Testicular cancer (TC) is diagnosed at a young age and carries a remarkably high cure rate. Hence, there is a sizeable population living in the survivorship phase. Many studies have highlighted the plight of TC survivors as a result of late side effects of different therapeutic modalities used for treatment of TC. This is the first study in Ireland to highlight the impact of TC on socio-economic health, sexual health, and fertility in survivors. We performed a questionnaire-based survey, fully anonymised to encourage participation. Questionnaires were designed to measure the self-reported impact on social, sexual, and economic health on a five-point Likert scale (ranging from no effect to very significant effect). Whereas, any effect on fertility was investigated with questions regarding biological children before and after cancer with or without medical assistance. A total of 83 TC survivors participated in the study. Almost half of our respondents revealed some effect on their performance at work and personal finances. Around one-third had an impact on career choice, job security, and their relationship with their partner. Regarding sexual health, the worst repercussions were noted on sex drive and body image perception, where close to half of the respondents reported at least some deterioration. Ejaculation and erectile function were affected in 30% of the participants. Of all participants, 17% reported issues with fertility, and the same proportion reported seeking medical help to conceive after diagnosis or treatment of TC. In conclusion, some TC survivors experience significant impact on their socio-economic and sexual health.

Abstract: Ivermectin (IVM) is a macrolide antiparasitic drug, and Metformin (MET) is a biguanide oral hypoglycemic drug. Studies have shown that both of them have obvious anti-tumor effects, but there have been no reports on the combined treatment of Canine breast tumors.This report aimed to investigate the effectiveness and the possible mechanism of drug combination on Canine breast cancers. Mouse breast tumor cells (4T1) and canine breast tumor cell (CMT-1211) were respec-tively treated with IVM, MET and their combination, and then cell viability was assessed. After that transcriptomic analysis was performed to study the action pathway of the drug combination on anti-tumor. Reactive oxygen species (ROS) levels were detected by flow cytometry, and au-tophagosome formation was observed by transmission electron microscopy (TEM). Immunoflu-orescence detected the cytoplasmic translocation of LC3B and P62 into the nucleus. Western blot detected the protein expressions of LC3B, P62, Beclin1, Bcl-2, p-PI3K, p-AKT, and p-mTOR. Our transcriptomic analysis showed that the combination of IVM and MET regulated the expression of autophagy-related genes and pathways, including the PI3K/AKT/mTOR signalling pathway. Our in vitro experiments showed that the combination of two drugs had a considerably significant effect on cytotoxicity, ROS levels, and the formation of autophagosomes compared to each drug alone. Meanwhile, in vivo experiments showed that It was observed that IVM combined with MET had obvious inhibitory effect on tumor growth in canine breast tumor xenografts. This study concluded that IVM with MET activated autophagy, which killed breast cancer cells by inhibiting the activation of the PI3K/AKT/mTOR pathway and promoting the excessive accumulation of ROS. It offers a theoretical foundation for the synergistic effects of MET and IVM to suppress breast cancer cell activity.

Abstract: Introduction: Glioblastoma (GBM) remains a clinical challenge due to its high recurrence rate and the difficulty of distinguishing true progression from treatment-induced changes. 18-fluoride-fluoro-ethyl-tyrosine positron emission tomography (FET-PET) can clarify ambiguous findings from standard imaging by assessing metabolic activity. The aim of this study was to evaluate both sensitivity and specificity of FET-PET positive findings referenced with the target lesion histology. Methods: We performed a retrospective, single-center study correlating PET findings with histopathological results during multiple GBM recurrences. A molecular subgroup analysis stratified by MGMT status was conducted for “true-positive” and “true-negative” PET findings. Results: 960 patients with GBM were treated at our department between 2006 and 2021, of whom 347 (36.1% of total) had one tumor recurrence during follow-up with 156 (45.0%) FET-PET scans available. 95 patients (9.9%) had a second recurrence with a FET-PET conducted in 37 of these (39.0%), whereas 23 patients (2.4%) had a third recurrence with a FET-PET available in 8 patients (34.8%). For a positive FET-PET finding, the sensitivity achieved 95%, 96% and 83% in the first, second, and third recurrences, respectively, while the specificity amounted to 13%, 0%, and 0%. Stratification by molecular subtype revealed no differences in sensitivity (p=0.498 first recurrence, p=1.0 for second recurrence) or specificity (p=1.0 first recurrence, p=1.0) for MGMT status. Conclusion: PET imaging demonstrated high sensitivity for detecting GBM recurrence but showed variable specificity depending on the classification of uncertain cases. Notably, sensitivity declined with an increasing number of recurrences, suggesting that cumulative treatment effects and greater tumor heterogeneity over time may affect diagnostic performance. Further prospective studies are needed to refine diagnostic thresholds and improve clinical decision-making.

Abstract: Thyroid carcinogenesis has multiple hallmarks, including evasion of tumor suppressors. Reactivation of wild-type p53 function is an ultimate goal in cancer therapy, which requires an understanding of the p53 suppression mechanism specific for the cancer type. MiR-7-5p and IPO7 are implicated in the pathogenesis of several human diseases. This work demonstrates the role of IPO7 supported by miR-7-5p in p53 regulation in papillary thyroid cancer cells. Primary cultured thyroid cells and FFPE thyroid tissues from PTC and benign cases were used. Functional experiments were performed by transfection with IPO7 siRNA or miR-7-5p mimic/inhibitor, followed by apoptosis and luciferase reporter assays, immunoblot assays and RT‒PCR. The expression and subcellular localization of IPO7, p53, MDM2, and ribosomal proteins (RPL11 and RPL5) were studied by immunofluorescence staining and confocal microscopy. The results show that IPO7 is overexpressed in PTC and regulated by miR-7-5p. Modulation of IPO7 expression in cultured thyroid cells altered the nucleocytoplasmic shuttling of p53, MDM2, RPL11 and RPL5 in addition to the p53 protein level and activity. The expression pattern of IPO7, p53 and MDM2 in cultured thyroid cells and clinical thyroid tissue specimens confirmed the association between IPO7 overexpression and reduced p53 stability in PTC. In conclusion, the data here show that p53 level and activity are differentially controlled in malignant and benign thyroid cells through miR-7-5P/IPO7-mediated regulation of RP-MDM2-p53 nucleocytoplasmic trafficking. In PTC, downregulation of miR-7-5p with consequent overexpression of IPO7 might be a protective mechanism used by cancer cells to evade p53 growth suppression during carcinogenesis.

Abstract: Background: Triple-negative breast cancer (TNBC) is the leading cause of death from neoplasms in women worldwide, related to a high rate of metastasis and low survival in patients. Bacterial cyclodipeptides (CDPs) have anticancer properties in several types of cancer in vitro as in vivo models, targeting several signaling pathways. Methods: The effect of the CDPs on TNBC MDA-MB-231 lines was evaluated in vitro as advanced-stage tumors developed and their ability to prevent the appearance of metastatic foci in the mammary tissue of mice model and bone structuration. Results: CDPs treatment decreased the migratory and invasive capacity of the TNBC MDA-MB-231 line in vitro more efficiently than methotrexate (MTX) (p>0.001). The anti-metastatic effect in the TNBC was associated with the down-regulation of the Akt/mTOR/S6K pathway and the metastasis markers such as Gab1 and Vimentin. MDA-MB-231 xenografted mice administrated with CDPs and combined with MTX showed a significant decrease in primary tumor development and metastatic foci (p>0.001). Likewise, the metastatic foci were observed in the lungs and liver, which were inhibited by CDPs. Metastasis markers p-Akt, Gab1, and FOX01 were significantly down-expressed in the tumor tissue of mice implanted with TNBC submitted to CDPs treatment. In addition, the metastatic behavior in the skeletal system was alleviated with the CDPs and CDPs+MTX treatments. Conclusions: The anti-metastatic effects of bacterial CDPs involve the phosphorylation inhibition of the Akt/mTOR/S6K pathway and the metastasis markers Gab1, Vimentin, and FOX01. The finding indicates that the CDPs, in combination with MTX, potentialize the anti-neoplastic property in TNBC, proposing the CDPs as a viable alternative in human breast cancer therapy.

Abstract: Background: Glioblastoma (GBM) remains a devastating brain malignancy characterized by cellular heterogeneity and therapy resistance. Cancer stem-like cells (CSCs) within GBM are implicated as drivers of tumor progression and resistance to the standard-of-care chemotherapy, temozolomide (TMZ). O⁶-methylguanine-DNA methyltransferase (MGMT) expression mediates resistance by repairing TMZ-induced DNA damage. Differentiation therapy offers a potential strategy to reduce the aggressive stem-like phenotype. All-trans retinoic acid (ATRA) is a known differentiating agent. We hypothesized that ATRA treatment could induce differentiation-associated changes in established GBM cell lines, leading to downregulation of stemness markers and the resistance factor MGMT. Methods: Two established human GBM cell lines, U87-MG and A172, were cultured under neurosphere-promoting conditions to enrich for potential stem-like subpopulations. Cells were treated with either 1 µM ATRA or vehicle control (DMSO) for 5 days. Total RNA was extracted, and cDNA was synthesized. Quantitative Real-Time PCR (qPCR) assessed relative mRNA expression levels of key stemness transcription factors (SOX2, NES) and the DNA repair gene MGMT. Gene expression was normalized to the geometric mean of two validated housekeeping genes (GAPDH, ACTB). Relative quantification was calculated using the ΔΔCt method, and statistical significance was determined using Student's t-tests. Results: ATRA treatment (1 µM, 5 days) resulted in a statistically significant downregulation of stemness marker expression in both GBM cell lines compared to vehicle controls. Specifically, SOX2 mRNA levels decreased by 3.7-fold (p=0.0008) in U87-MG and 2.9-fold (p=0.0041) in A172 cells. NES mRNA levels decreased by 4.1-fold (p=0.0005) in U87-MG and 3.3-fold (p=0.0028) in A172 cells. Crucially, ATRA treatment also led to a significant reduction in MGMT mRNA expression. MGMT levels decreased by 2.6-fold (p=0.0065) in U87-MG and 2.2-fold (p=0.0132) in A172 cells following ATRA exposure. Conclusion: Our findings demonstrate that ATRA treatment reduces the expression of stemness-associated genes SOX2 and Nestin in established GBM cell lines cultured under neurosphere conditions. Importantly, ATRA concurrently downregulates MGMT mRNA. These results provide a molecular rationale for exploring ATRA-induced differentiation as a strategy to potentially modulate TMZ resistance pathways in GBM models, warranting further investigation into its therapeutic potential, particularly in combination therapies.

Abstract: It is not widely known that the human genome retains ancestral emergency programs that can be activated in response to germline stress and irreparable DNA damage, freeing affected cells from the constraints of multicellularity. The reactivation of unicellular genome modules—via a process known as the multicellular-to-unicellular transition (MUT)—represents an ancient mechanism rooted in the gradual back-and-forth transition to multicellularity. MUT modules are preserved in a reactivatable state within the genomes of all metazoans and are activated in approximately 50% of humans, particularly at advanced stages of life. This inversion to a unicellular genome state gives rise to a subpopulation of precancerous cells that proliferate through defective symmetric cell division (DSCD). Once DSCD progeny acquire fusibility, they form hyperpolyploid genome repair syncytia (MGRS), which work to eliminate genomic defects and establish a unicellular cancer stemgermline capable of producing committed, non-proliferative cancer stem cells. Similar to the Ur-germline of unicellular ancestors, the cancer stemgermline, along with its clones and sublines, is hypoxic and becomes dysfunctional in tissues with oxygen levels above 6.0% O₂, a condition referred to as germline hyperoxia. Together with a somatic helper lineage that does not generate cancer stem cells, the stem-germline forms an autonomous cellular system that functions according to the principles of unicellular life. The stem-germline and its somatic counterpart work in concert to maintain and expand a stable, unicellularized stemgermline genome

Abstract: Thyroid cancer (TC) is a common malignancy that accounts for approximately 1% of all human cancers. Given their anatomical proximity to the thyroid, the parathyroid glands (PTG) are theoretically at risk of tumor involvement. However, PTG metastases are rare and may be underdiagnosed because of routine PTG preservation during thyroidectomy. This study aimed to identify cases of PTG invasion by TC through a 10-year retrospective review at Chosun University Hospital, along with an analysis of the existing literature. Among 1,032 thyroidectomies, PTG involvement was detected in 10 cases (0.97%). The affected patients included nine females and one male, with a mean age of 46 years (range: 25-77 years). Histological examination confirmed papillary thyroid carcinoma (PTC) in all cases. Tumor invasion into the perithyroid soft tissues was observed in nine patients, and central cervical lymph nodes metastases were present in four. All patients exhibited PTG pattern A (direct invasion). Based on our findings and literature data, PTG involvement by TC has an incidence rate of 0.05–3.9%, predominantly affects women in their sixth to seventh decade of life, and appears to no impact on prognosis unless accompanied by extensive extrathyroidal invasion. Further studies are necessary to determine whether PTG invasion should be integrated into the TNM staging system and to assess its prognostic and therapeutic implications.

Abstract: Osteosarcoma (OSA) is a naturally occurring, malignant bone tumor in both humans and canines, characterized by aggressive local behavior and a high propensity for metastasis. Despite advances in diagnostic methods and therapies, long-term survival rates have remained stagnant, underscoring the great need for the development of biomarkers serving in the prognosis and diagnosis of OSA across species. Biomarkers, molecular indicators of disease presence or progression, are pivotal tools in oncology, offering the potential to determine risk stratification, guide targeted therapies, and monitor treatment response. 
This review provides an in-depth analysis of the current landscape of OSA biomarkers, highlighting diagnostic and prognostic markers identified across species. We highlighted the role of biomarkers in osteosarcoma diagnosis and prognosis, and categorized them across multiple domains, including protein, cellular, metabolic, imaging, genetic, and epigenetic markers. Furthermore, we explore the utility of the canine model in osteosarcoma research, emphasizing its relevance to human OSA due to comparable diagnostic approaches, prognostic indicators, and clinical manifestations. With this review, we aim to demonstrate that integrating biomarker research across species can deepen our understanding of osteosarcoma pathogenesis and advance knowledge of its underlying biology, ultimately paving the way for precision medicine strategies that benefit both human and veterinary oncology.

Abstract: Background: Ovarian clear cell carcinoma (OCCC) represents a distinct histological subtype with high prevalence in Asian populations and poor chemotherapy response. PTEN, ARID1A, PD-L1, and mismatch repair (MMR) proteins have demonstrated clinical significance in cancer progression and treatment response. This study investigated molecular interactions between these biomarkers in Asian OCCC patients. Methods: Immunohistochemical analysis was performed on tissue microarrays from 69 OCCC cases. Expression of PTEN, ARID1A, PD-L1, and four MMR proteins were evaluated alongside clinical data. Results: We observed high prevalence of PTEN loss (78.3%) and ARID1A deficiency (48.8%), with PD-L1 expression in 26.1% and MMR deficiency in 10.1% of cases. All PD-L1-positive tumors demonstrated concurrent PTEN loss (p=0.007). MMR deficiency was significantly associated with ARID1A loss (p=0.049). PTEN loss correlated with worse progression-free survival in early-stage disease (p=0.039). Concurrent retention of both ARID1A and PTEN occurred in only 3 cases (6.8%). Conclusions: PTEN and ARID1A alterations represent early pathogenic events in Asian OCCC, with PTEN loss significantly impacting progression-free survival in early-stage disease. The correlation between PTEN loss and PD-L1 expression, alongside the association between ARID1A and MMR deficiency, provides new insight into OCCC's immunological landscape and potential therapeutic vulnerabilities.

Abstract: Intermediate and advanced-stage hepatocellular carcinoma (HCC) continues to present significant therapeutic challenges. Hepatic artery infusion chemotherapy (HAIC), a well-established locoregional treatment for unresectable HCC, has recently demonstrated promising clinical outcomes both as monotherapy and in combination with systemic therapies. This comprehensive review examines recent clinical advances in HAIC for HCC, with particular emphasis on evolving treatment regimens and their therapeutic efficacy.

Abstract: Introduction: The treatment of MBC patients is guided by receptor status, with re-biopsy at relapse recommended to reassess hormone receptor (HR) status. Various treatment options are available for HER2- MBC, including CDK4/6 inhibitors, PARP inhibitors, and checkpoint inhibitors. The study highlights the importance of determining receptor subtype for guiding treatment choices. Patients and Methods: The GIM 13 AMBRA study is a longitudinal cohort study involving 42 centers in Italy. It includes data from 939 HER2- MBC patients enrolled between May 2015 and September 2020. The study analyzes the impact of HR expression changes on clinical outcomes using Kaplan-Meier survival curves and other statistical methods. Results: Among the 939 patients, 588 were re-biopsied at first relapse. The study found no significant differences in disease-free survival (DFS), progression-free survival (PFS), or overall survival (OS) between patients whose tumors changed molecular subtype and those who did not. However, post-progression survival from first-line treatment (PPS1) was different between the two groups. Discussion: The study confirms the phenomenon of receptor discordance between primary tumors and metastases. It emphasizes the need for re-biopsy in recurrent MBC to guide treatment strategies. The findings align with previous studies and highlight the importance of understanding receptor changes for improving patient outcomes. Conclusion: The GIM 13 AMBRA study provides valuable insights into the impact of molecular subtype changes on survival outcomes in Luminal MBC patients. It underscores the importance of re-biopsy and personalized treatment strategies in managing metastatic breast cancer.

Abstract: MicroRNAs belong to a class of small non-coding RNA molecules that regulate gene expression post-transcriptionally. By binding to specific mRNA sequences, microRNAs can either inhibit translation or promote transcript degradation. MicroRNA-28 (miR-28) plays a pivotal role in regulating the processes responsible for the pathogenesis of nu-merous diseases. Its function is contingent upon the specific type of disease and the cellular microenvironment. miR-28 can act as both an inhibitor and inducer of pathogenic pro-cesses. This article discusses the impact of miR-28 on the progression of various types of cancer, with particular emphasis on its role as a regulator of gene expression involved in cell proliferation, apoptosis, as well as invasion, migration, and metastasis. Additionally, the article delves into the role of miR-28 in other human diseases and its influence on the processes that underlie their development. A comprehensive understanding of the pre-cise mechanisms through which this specific microRNA exerts its regulatory functions could significantly impact the development of novel therapies. Furthermore, there is a possibility that miR-28 could be utilized as a diagnostic and preventative biomarker.

Abstract: Background/Objectives: To investigate the changes of ER and PR in the epithelium and stroma of normal and neoplastic uterine cervix. Methods: Two pathologists independently scored the expression levels of ERα, PR(A+B), and PRB in the stroma and epithelium of normal, cervical intraepithelial neoplasia grade 2 and 3 (CIN2/3), carcinoma in situ (CIS), and invasive cervical carcinoma (ICC) specimens. Results: Sex hormone receptors were abundantly expressed in the stroma compared to the epithelium or carcinoma of the cervix. Stromal ERα was progressively upregulated during cervical carcinogenesis, with immunoreactive scores (IRS) of 1.3 ± 1.5, 2.1 ± 1.9, and 3.6 ± 3.3 in the CIN2/3, CIS, and ICC groups, respectively (p < 0.001). By contrast, epithelial PR(A+B) and PRB were downregulated, with IRS of 0.4 ± 0.7 and 0.5 ± 0.8, 0.1 ± 0.4 and 0.2 ± 0.6, and 0.1 ± 0.6 and 0.1 ± 0.4 in the CIN2/3, CIS, and ICC groups, respectively (p < 0.001). During CIN2/3 transition, the coexpression relationship between ERα and PRs began to break down. Although epithelial PR(A+B) was downregulated, stromal PR(A+B) and PRB were upregulated. After complete transformation, the stromal PRB was significantly upregulated, and its loss was related to more distant metastasis and poorer prognosis. Conclusions: The results of this study highlight the carcinogenic role of stromal ERα, the tumor suppressor role of epithelial PRs, and the importance of stromal PRB in the development of cervical cancer; they can be used as a basis for developing prevention and treatment strategies for this disease.

Abstract: Stereotactic radiotherapy (SBRT) and radiofrequency ablation (RFA) are common ablative techniques for lung metastases. Retrospective review of all patients treated with either modality at a single institution between 2011 and 2019 was conducted. Baseline characteristics and outcomes were compared. Local and distant progression, and overall survival were estimated using the Kaplan Meier method. Univariable analysis was carried out using Cox regression followed by multivariable modeling. 106 patients treated with RFA and 70 treated with SBRT were identified. Tumours treated with SBRT were larger (median size 18 vs 11mm) and primarily oligometastatic (91.4% vs 20%). Median progression-free survival (PFS) was 12.5 months for SBRT and 7.9 months for RFA (p=0.009). Median OS was similar (p=0.66). In multivariable analysis, lesion size >20mm was predictive of adverse local PFS (p=0.001), PFS (p=0.0034) and OS (p=0.001). Statistically significant interaction effect suggested RFA offered better local PFS compared to SBRT within colorectal primary patients (p=0.035). This study highlights differences in patient baseline characteristics, selection and outcomes for RFA or SBRT in the treatment of lung metastases at our institution. Future studies for SBRT should focus on the radiosensitivites of individual tumour types and the optimum dose schedules required for differing histologies. For less radiosensitive tumours, RFA may offer a superior alternative.

Abstract: Background: Breast cancer exhibits profound molecular heterogeneity, with distinct biological features, therapeutic responses, and prognostic outcomes across subtypes. However, a unifying feature of all breast cancers is their adipocyte-enriched microenvironment. Dysregulated lipid metabolism drives tumor progression in all subtypes, supporting the development of a universal prognostic model independent of molecular classification. Methods: Prognostic fatty acid metabolism-related genes were identified in the training set using univariate Cox regression. LASSO regression refined these genes to construct the Fatty Acid Metabolic Signature for Prognosis (FAMOUS), enabling risk stratification. FAMOUS’s prognostic utility was validated in the testing set and external cohort, and across molecular subtypes and therapies. Results: FAMOUS comprises 15 genes. High FAMOUS scores independently predicted poor overall survival in the training set (HR=4.97, 95% CI: 3.17-7.79; p&lt;0.001), testing set (HR=7.39, 95% CI: 2.19-24.97; p=0.001), and GSE72245 (HR=7.97, 95% CI: 3.39-18.75; p&lt;0.001), after adjusting for molecular subtype, stage, and age. It stratified risk across Luminal A, Luminal B, HER2+, and TNBC subtypes and retained prognostic value in patients receiving chemotherapy, radiotherapy, endocrine therapy, or trastuzumab. High FAMOUS scores correlated with immune-suppressive microenvironments, marked by downregulated immune-related pathways and altered immune cell infiltration (e.g., reduced CD8+ T cells, enriched M2 macrophages), suggesting implications for immunotherapy patient stratification. Conclusions: FAMOUS is a novel, pan-subtype prognostic tool for breast cancer, transcending molecular classification and therapeutic modalities.

Abstract: This case highlights the clinical value of 4D-PET/CT for accurate target delineation in SBRT re-irradiation of a central lung recurrence within post-radiation fibrosis. Motion-resolved imaging revealed significant underestimation of the target volume using static PET alone, and its integration enabled safe, effective treatment with favorable metabolic response and excellent tolerance.

Abstract: Melanoma remains one of the most aggressive and treatment-resistant malignancies, despite advances in targeted therapies and immunotherapies. Drug resistance continues to be a major challenge, limiting long-term therapeutic success. Epigenetic regulators, particularly histone deacetylases (HDACs), play a crucial role in melanoma progression and therapy resistance by modulating gene expression, chromatin accessibility, and non-histone protein functions. HDACs influence key oncogenic pathways, including the MAPK, PI3K/AKT, and WNT/β-catenin signaling cascades, contributing to resistance against BRAF/MEK inhibitors and immune checkpoint blockade therapies. HDACs also modulate the tumor microenvironment by regulating immune cell infiltration, cytokine production, and stromal interactions, thereby promoting an immunosuppressive milieu that supports tumor survival. Given their pivotal role in drug resistance, HDAC inhibitors (HDACis) have emerged as promising therapeutic agents. HDACis induce apoptosis, suppress tumor proliferation, and enhance immune responses by reactivating tumor suppressor genes and modulating epigenetic landscapes. Preclinical and clinical studies indicate that combining HDACis with existing therapies, such as BRAF/MEK inhibitors or immune checkpoint inhibitors, can overcome resistance and improve treatment efficacy. Despite their potential, challenges remain, including toxicity, patient selection, and the identification of optimal combination strategies. Ongoing research aims to develop selective HDACis with improved efficacy and reduced adverse effects. This review comprehensively explores the role of HDACs in melanoma drug resistance, their interaction with key signaling pathways, and the therapeutic potential of HDAC inhibition. A deeper understanding of HDAC-mediated resistance mechanisms will aid in developing novel strategies to enhance melanoma treatment outcomes and overcome therapeutic resistance.

Abstract: Gliomas diagnosed during pregnancy are rare and there are no established guidelines for their management. Effective treatment requires a multidisciplinary approach to balance maternal health and pregnancy preservation. We here present a case of rapidly progressing glioma in a 33-year-old pregnant woman. The patient initially presented with a generalized tonic-clonic seizure at 21 weeks' gestation. Imaging revealed a tumor in the right cerebral lobe, involving both cortical and subcortical structures, while magnetic resonance spectroscopy suggested a low-grade glioma. The patient remained clinically stable for two months, but then developed severe headaches; MRI showed a worsening mass effect. At 34 weeks' gestation, an emergency and premature caesarean section was performed under general anesthesia. The patient then underwent a craniotomy for maximal tumor resection, which was histologically and molecularly diagnosed as IDH wild-type glioblastoma. Using qPCR, we found that the glioblastoma tissue showed upregulated expression of genes involved in cell structure (GFAP, VIM) and immune response (SSP1, TSPO), as well as increased expression of genes related to potential hormone response (AR, CYP19A1, ESR1, GPER1). After surgery, the patient showed resistance to Stupp protocol therapy and is currently receiving combination therapy with lomustine and bevacizumab. This case illustrates the aggressive nature and rapid progression of glioblastoma during pregnancy.

Abstract: Rhabdoid tumours (RTs) are aggressive neoplasms most often characterised by biallelic loss of the SMARCB1 gene, which encodes a core subunit of the SWI/SNF chromatin remodelling complex. Despite their relative genetic stability, RTs exhibit a highly malignant phenotype and poor prognosis. This review aims to explore the mechanisms underlying SMARCB1 aberrations, their role in driving hallmarks of cancer, and emerging therapeutic strategies for RTs. The loss of SMARCB1 drives multiple cancer hallmarks by disrupting key regulatory pathways. It promotes unchecked cell proliferation through alterations in p16INK4a and Myc signalling. SMARCB1-deficient tumours possess immune evading capabilities via PD-L1 overexpression and immune checkpoint activation. SMARCB1 deficiency also alters cellular energetics by various mechanisms. The nucleotide biosynthesis pathway has been demonstrated to be upregulated in RT organoids, as shown by increased levels of pathway metabolites. Enzymes of the mevalonate pathway such as HMG-CoA reductase and mevalonate kinase are also dysregulated. Targeting glutathione metabolism with eprenetapopt may result in oxidative stress and induce apoptosis in RTs. Widespread epigenetic aberrations, including increased EZH2 activity, are being targeted with inhibitors such as tazemetostat. Future horizons in RT treatment include immunotherapies, epigenetic modifiers, and gene therapies. The synergy and optimal timing of targeted therapy with conventional treatment needs to be better characterised in order to proceed to later stage clinical trials and clinical practice.