The tumor microenvironment (TME) plays a pivotal role in cancer progression by orchestrating interactions between cancer cells and surrounding immune and non-immune cells through metabolic reprogramming. Methylation-controlled J protein (MCJ; also known as DNAJC15) is a negative regulator of mitochondrial respiration, but its role in tumor metabolism remains unclear. To study the role of tumor-intrinsic MCJ expression, we generated MCJ-deficient cancer cell lines using siRNA and performed a comprehensive analysis of their characteristics in comparison with MCJ-expressing parental cells. MCJ deficiency resulted in enhanced mitochondrial respiration and ATP production. Despite normal growth in vitro, MCJ-deficient tumor cells exhibited severly curtailed growth in immunocompetent mice. However, these cells grew comparably to controls in T-cell-deficient athymic mice, indicating immune-mediated suppression. Tumors lacking MCJ exhibited increased immune cell infiltration and immunogenicity, as determined by immunohistochemistry and flow cytometry. Transcriptomic analysis revealed a metabolic shift from glycolysis-dominant and hypoxic conditions to a state favoring oxidative phosphorylation, which correlated with upregulation of immune-related pathways and enhanced anti-tumor immune responses. Bioinformatic analysis conducted to study the correlation between the level of MCJ expression and tumor functions in human colorectal cancer revealed that low MCJ expression correlated with increased tumor mutational burden, microsatellite instability, and immune cell infiltration, demonstrating the clinical relevance of MCJ expression in the context of colon adenocarcinoma. These findings suggest MCJ as a promising target for metabolic immunotherapy in cancer.

Although the tissue-agnostic FDA approval of pembrolizumab for tumor mutational burden (TMB)-high tumors has provided meaningful clinical benefit to patients, there remains a need to optimize TMB assessment. In this cohort study, we investigated the discordance between whole-exome sequencing (WES) and panel-based methods and evaluated their relative clinical utility in identifying patients likely to benefit from pembrolizumab. Molecularly-profiled tumors from patients treated with pembrolizumab were analyzed (N = 26,756). TMB was calculated using WES data or panels of genes (324, 523, and 648) from commercially available assays (TMB-High ≥ 10 mutations/Mb). Pembrolizumab-specific overall survival (OS) was calculated from insurance claims data (treatment start to last contact). Targeted gene panels tended to overestimate TMB and demonstrated ~ 10-15% discordance in binary TMB calls from WES, which was most pronounced for the smallest panel. Discordant cases for all three panels clustered near the TMB clinical calling threshold. WES offered improved stratification of patients for pembrolizumab treatment: in a subset of "TMB-reliant" tumor types lacking disease-specific immune checkpoint inhibitor (ICI) indications (n = 3,981), median OS was approximately 5 months longer for cases identified as WES-TMB-High but panel-TMB-Low compared to those identified as WES-TMB-Low but panel-TMB-High (p < 0.05 for 324-gene and 648-gene panels). Approximately, 10-11% of patients were potentially misclassified by panels. These findings emphasize the importance of broader gene representation for accurate TMB determination near the clinical threshold-especially in tumor types lacking disease-specific ICI indications, where tissue-agnostic MSI-High/dMMR or TMB-High labeling represents the principal on-label route to ICI therapy.

Single-cell mechanical properties such as stiffness, elasticity, and viscosity, are crucial in governing biological processes like migration, proliferation, and differentiation. In cancer, the mechanical properties of cells undergo significant alterations, which contribute to tumor growth, metastasis, and resistance to therapy. This review focuses on cancer cell stiffness and explores how its regulation is disrupted by the complex interplay among cytoskeletal remodeling, nuclear mechanics, and extracellular matrix (ECM) interactions. Cancer-associated fibroblasts (CAFs) and ECM composition within the tumor microenvironment (TME) modulate cellular mechanics via mechanotransduction pathways involving Yes-associated protein/transcriptional coactivator with PDZ-binding motif (YAP/TAZ) and integrin-focal adhesion kinase (FAK) signaling. Increasing evidence supports cell stiffness as a promising diagnostic and prognostic biomarker, as well as a predictor of treatment response. Therefore, advanced techniques for measuring cell stiffness such as atomic force microscopy (AFM), Brillouin microscopy, and acousto-holography are evaluated with a focus on their potential clinical applicability. However, translation into routine oncology practice remains limited by technical variability, lack of standardized protocols, and the need for large-scale clinical validation. This review highlights the potential of integrating biomechanical markers into clinical workflows as a means to advance cancer diagnostics and enable more personalized therapeutic strategies.

Prostate cancer (PCa) remains a major global health burden. Although androgen deprivation and receptor-targeted therapies initially benefit patients, resistance often leads to metastatic castration-resistant prostate cancer, with limited treatment options. Aldehyde dehydrogenase 7A1 (ALDH7A1) is an emerging oncogenic driver of PCa, but selective inhibitors are lacking. Here, we report irreversible ALDH7A1 inhibitors targeting the catalytic Cys330, identified from a library of 3-bromo-4,5-dihydroisoxazole derivatives. These compounds show minimal inhibition of ALDH4A1 and GAPDH, supporting selectivity for ALDH7A1. Compounds 3b and 4b reduced DU145 cell viability (low μM IC₅₀), impaired migration, and altered the cell cycle. No significant effects were observed in LNCaP cells (low ALDH7A1 expression) or Hs27 fibroblasts. Treatment of DU145 cells resulted in the inhibition of intracellular ALDH activity and accumulation of malondialdehyde, consistent with increased oxidative stress. These findings validate ALDH7A1 as a druggable target and introduce a new chemical space for selective covalent ALDH inhibitors in oncology.

A childhood cancer diagnosis creates a profound crisis for the entire family. While the psychological distress of this journey is well-documented globally, the lived experiences of families within the specific socio-political and economic context of Iran remain underexplored.

This study aimed to explore the lived experiences of Iranian families caring for a child with cancer.

A hermeneutic phenomenological study was conducted in Urmia, Iran. Through purposive sampling, 19 family members (parents and siblings) of children with cancer were recruited. Data were collected over an 8-month period (November 2023-June 2024) via in-depth, semi-structured interviews. The data were analyzed using the Van Manen approach and managed using MAXQDA software. Trustworthiness was ensured through strategies such as peer debriefing with an external qualitative researcher and maintaining a detailed audit trail of all analytical decisions.

The analysis yielded 2433 codes, categorized into 14 sub-themes and 5 main themes: (1) psychological and emotional concerns, (2) physical and medical concerns, (3) family challenges, (4) support systems as an important asset, and (5) spiritual experiences. These findings were experienced under the pervasive shadow of sanctions and the threat of war.

The experience of caring for a child with cancer in Iran is deeply shaped by the interplay of intense emotional suffering and significant structural challenges, including economic pressure and limited support systems. The findings underscore the critical need for culturally sensitive psychosocial support and policy interventions that address the unique socio-economic vulnerabilities of these families.

Despite improving survival rates, the complexity of post-operative survivorship for oesophageal cancer patients remains poorly understood. This mixed-methods review explores quantitative health-related quality-of-life (HRQoL) outcomes and qualitative survivor experiences to provide a comprehensive, person-centred perspective.

A convergent synthesis framework was employed to examine patient perspectives on survivorship following oesophageal cancer resection. A systematic search of the literature was undertaken across four databases to identify studies reporting EORTC QLQ-C30 and QLQ-OES18 outcomes and qualitative research exploring post-operative experiences. Quantitative studies underwent random-effects meta-analysis to examine HRQoL trajectories from baseline to 5 years post-operatively. Qualitative studies underwent thematic synthesis following Thomas and Harden's established three-stage framework.

Fifty-seven studies were included, consisting of 40 quantitative and 17 qualitative studies. HRQoL followed a triphasic pattern with a marked deterioration at 6 months, partial recovery by 12-36 months, followed by a plateau with persistent symptoms at 5 years. Reflux, eating restriction and fatigue were the most prevalent symptoms following oesophagectomy. Thematic synthesis identified five domains of oesophageal cancer survivorship; digestive disruption, physical impairment, psychosocial impact, navigating healthcare and support systems, and striving for normalcy. Qualitative accounts revealed challenges under-represented in quantitative measures, including an altered relationship with food, fear of recurrence, as well as identity loss.

Post-oesophagectomy survivorship is a sustained process of adaptation, not a return to baseline health. Current oncology-centred care models overlook chronic, multidimensional needs of patients. Integrated survivorship pathways combining nutritional support, rehabilitation, and psychosocial support are essential to restore agency and improve long-term wellbeing.

Prostate cancer (PCa) stands as one of the primary cancer diseases affecting male health and represents the principal reason behind death when metastasis develops during late-stage disease. The spread of prostate cancer from its initial site demands intricate molecular interactions through signaling pathways which permit cancer cells to break their attachment to the original tumor mass and form secondary tumor sites in distant organs. Prostate cancer metastasis depends heavily on three main molecular pathways which include the PI3K/AKT signaling cascade along with Wnt/β-catenin pathway and epithelial-mesenchymal transition (EMT) signaling mechanisms. The deregulation of these signaling pathways creates strong contributions toward prostate cancer spread during metastasis and reduction of response to standard treatment methods. Presently available androgen deprivation therapy and chemotherapy have proven successful to some extent yet insufficient for effective treatment of both castration-resistant prostate cancer (CRPC) and metastatic disease. The development of therapies which block AKT signaling combined with Wnt signaling inhibition and reversal of EMT processes creates new treatment opportunities for better cancer outcome results. The combined use of immunotherapy with personalized medicine along with liquid biopsy technologies will improve therapeutic effects by enabling real-time tracking of disease evolution and treatment response. This analysis investigates the molecular processes that drive prostate cancer metastasis and the present therapeutic solutions and the upcoming therapies that try to block these pathways. Numerous treatment approaches and precision medicine strategies combining the integrated treatment approaches may lead to improved therapeutic benefit with fewer adverse effects while delivering more personalized and effective care. This review will majorly focus on the molecular pathways and preclinical treatment options that support metastatic prostate cancer, but briefly outline the clinical progress that is currently shaping the precision therapeutic models.

Cancer cells rewire their metabolism to sustain a high proliferation rate. Sensing external cues is essential to match the metabolic fluxes of the cells to the external stimuli. As part of the glucose metabolism, the hexosamine biosynthesis pathway (HBP) is considered a nutrient-sensing pathway. The HBP produces UDP-GlcNAc, a key precursor for N-linked glycosylation, O-linked glycosylation, and O-GlcNAcylation. These post-translational modifications can influence protein folding, interactions, and subcellular localization. Altered glycosylation of oncogenic proteins has been linked to the acquisition of malignant properties. In this review, we outline the current knowledge of molecular alterations and the prognostic role of the expression of HBP enzymes in sarcoma. We catalog the known sites of N-/O-linked glycosylation and O-GlcNAc modifications in molecular drivers of mesenchymal tumors, and discuss the potential effect of these modifications on protein function. We also summarize the studies that examined the effect of the HBP inhibitors in preclinical models of cancer, and explore the potential of the HBP inhibition as a novel therapeutic approach for sarcoma. Finally, we present recent progress in drug development for targeting the HBP, and delineate the key technological innovations needed to accelerate the preclinical and clinical research on pharmacological inhibition of the HBP.

Radiotherapy is a complex, multistage process that involves collaboration across professional disciplines (radiographers working in pre-treatment preparation, physicians, physicists, radiation therapists during planning and treatment. While severe errors are uncommon, they can have profound consequences for patients. The Danish Society for Medical Physics supports a Special Interest Group dedicated to improving patient safety by analysing unintended events (UEs) and near misses in radiotherapy. Here we report on the work conducted with an updated system for categorising UEs in radiotherapy in Denmark.

An updated reporting system based on the English Radiotherapy Pathway Coding (RPC) system has been taken into use in 2025. This system, including the use of a Danish system that ranks the UEs from the patients perspective, called Patient Centred Coding, is outlined and UEs reported in 2025 are summarised.

Radiotherapy is generally a safe treatment modality, a conclusion further supported by our results from 2025. In 2025 only 339 UEs were reported, 315 of these with low risk and 24 with medium risks. The lesson learned is that the main focus in order to prevent the most harmful UEs should be on the delineation and the planning process.

Based on our experience from this work, we recommend the development of a national system for categorising and ranking UEs. We further recommend establishing a national working group that meets regularly and focuses on UEs at a national level.

Mesonephric adenocarcinomas are rare neoplasms derived from remnants of the paired mesonephric ducts. Neoplasms arising from the uterine corpus that are morphologically and immunohistochemically similar to true mesonephric carcinomas, but do not arise from mesonephric remnants, are termed "mesonephric-like" adenocarcinomas. The diagnosis of mesonephric-like adenocarcinoma is pathologically challenging. These tumors often exhibit a mixture of morphologic patterns of more common adenocarcinomas. Although their morphologic, immunohistochemical, and molecular profiles have been recently defined, much remains unknown about mesonephric-like adenocarcinomas. A better understanding of mesonephric-like andenocarcinoma's pathogenesis and molecular classification is needed to improve diagnosis and guide management of this rare and aggressive subtype of endometrial cancer. An updated International Federation of Gynecology and Obstetrics (FIGO) staging system for endometrial carcinoma was introduced in June 2023, upstaging aggressive histological subtypes such as mesonephric-like adenocarcinoma. In this report, we describe a patient with mesonephric-like adenocarcinoma arising in the uterine corpus, highlight the clinical significance of 2023 FIGO restaging, and discuss the multidisciplinary approach to treatment.