Objectives: Combretastatin A-4 (CA-4) is a microtubule-disrupting agent with established anti-tumor properties. This study aimed to evaluate the effects of CA-4 on key metastatic traits of cancer cells, including migration, clonogenic potential, cytoskeletal protein expression, and microtentacle (McTN) formation, using multiple cancer cell models, including the colon patient-derived circulating tumor cell line CTC-MCC-41. Methods: H1299 (non-small cell lung cancer), MDA-MB-231 (triple-negative breast cancer), HT-29 (colorectal cancer), and CTC-MCC-41 (derived from the blood of a colon cancer patient) cells were treated with CA-4 (10 μM) for 24 and 48 h. Colony formation was assessed with a clonogenic assay. Migration assays (Boyden chamber) evaluated cell motility, while cell viability was determined via MTT assay. Western blot analysis examined vimentin and α/β-tubulin expression. TetherChip assay analyzed McTN formation using wheat germ agglutinin (WGA) staining. Results: CA-4 treatment significantly reduced cell viability, colony formation, and migration across all tested cancer cell lines. Western blot analysis revealed a marked reduction in vimentin and α/β-tubulin expression after 48 h of treatment, indicating disruption of cytoskeletal integrity. In addition, TetherChip analysis demonstrated a pronounced decrease in McTN formation following CA-4 exposure, suggesting inhibition of cytoskeletal protrusions associated with metastatic dissemination. Conclusions: CA-4 effectively impairs multiple cancer cell functions related to metastatic progression, including proliferation, migration, cytoskeletal organization, and McTN formation. These findings highlight the potential of CA-4 as a microtubule-targeting agent with anti-metastatic activity, particularly in circulating tumor cells.

Background: Collecting duct carcinoma (CDC; Bellini duct carcinoma) is a rare, aggressive renal cancer with no established standard of care, and evidence for immune checkpoint inhibitor (ICI)-based therapy in CDC remains emerging and fragmented. We aimed to systematically synthesise efficacy and safety data on immunotherapy in adult patients with CDC. Methods: PubMed and Web of Science were searched from inception to 29 March 2025, with targeted post-search monitoring of key journals and ClinicalTrials.gov updated on 11 April 2026. Prospective interventional studies, observational cohorts/registries, and case series/reports were eligible. Screening, extraction and risk-of-bias appraisal (Joanna Briggs Institute tools) were performed independently in duplicate; results were narratively synthesised. Results: Overall, ICIs-particularly combinations-showed clinically meaningful activity in a subset of CDC patients. Twenty-four studies met criteria (2 prospective trials, 8 observational cohorts, 14 case-level publications/16 patients). The SUNNIFORECAST randomised phase II trial reported a CDC-specific ORR of 40% with ipilimumab + nivolumab versus 20% with standard of care (n = 9 CDC). Observational evidence yielded ORR ~10-44% and mOS ~13-42 months depending on regimen, with the highest activity seen with ICI plus TKI combinations. Durable complete responses (≥3-6 years) were documented at case level with dual checkpoint blockade and anti-PD-1 monotherapy. Safety was generally manageable, though serious events occurred sporadically (immune-mediated hepatitis; one fatal pneumonia). Conclusions: ICIs-particularly combination strategies-demonstrate clinically meaningful activity in selected patients with CDC, but evidence is limited by small samples, heterogeneity and high risk of bias. Prospective, biomarker-informed CDC-dedicated trials and coordinated registries are needed.

Cholesterol metabolism is central to cancer biology, influencing tumour initiation, progression, and therapeutic response, while contributing to the increased cardiovascular risk observed in cancer patients. Epidemiological studies investigating the relationship between circulating cholesterol levels and cancer risk have yielded conflicting results, reflecting substantial biological heterogeneity, tumour-specific metabolic demands, and methodological biases such as reverse causality. At the cellular level, malignant cells exhibit elevated cholesterol uptake and synthesis to sustain membrane biogenesis, lipid raft-dependent oncogenic signalling, and rapid proliferation. Cholesterol and its oxidized derivatives further modulate inflammation, angiogenesis, immune evasion, and key signalling pathways. Anticancer therapies profoundly disrupt lipid homeostasis; conventional chemotherapies, targeted therapies, hormone-modulating agents, and immunotherapies can induce dyslipidaemia and accelerate atherosclerotic disease, thereby contributing to long-term morbidity in cancer survivors. Conversely, lipid-lowering therapies-particularly statins-have emerged as pivotal tools in cardio-oncology, primarily for cardiovascular protection. Beyond this role, growing evidence suggests potential adjunctive antitumor effects mediated through inhibition of the mevalonate pathway, blockade of oncogenic signalling, and modulation of the tumour microenvironment. Novel agents, including ezetimibe, bempedoic acid, and proprotein convertase subtilisin-kexin type 9 inhibitors, provide additional therapeutic options, with emerging evidence supporting their immunomodulatory and anticancer properties, especially in combination with immune checkpoint inhibitors. Cholesterol metabolism plays a critical role in both CV disease and cancer biology, with growing evidence suggesting a complex bidirectional relationship between lipid homeostasis and tumour development. In addition, several anticancer therapies may profoundly affect lipid metabolism, thereby contributing to CV risk in cancer patients. The aim of this review is to provide a comprehensive overview of the interplay between cholesterol metabolism and cancer, to summarize the lipid-modifying effects of anticancer therapies, and to discuss the potential role of lipid-lowering strategies within the evolving framework of cardio-oncology care.

Programmed cell death regulates the tumor immune microenvironment. A comprehensive synthesis of how multiple programmed cell death pathways collectively orchestrate the remodeling of the urological immune landscape is currently lacking. This review summarizes and discusses how diverse programmed cell death modes, including ferroptosis, pyroptosis, autophagy, PANoptosis, necroptosis and cuproptosis, regulate immune evasion or activation in a context-dependent manner. Current preclinical evidence suggests that necroptosis, pyroptosis, and cuproptosis may enhance anti-tumor immunity by facilitating the release of damage-associated molecular patterns and increasing the infiltration of functional CD8⁺ T cells and dendritic cells, thereby potentially improving responses to immunotherapy. At the same time, several programmed cell death pathways display exhibit pronounced context dependence. In renal cell carcinoma, ferroptosis exhibited a functional contradiction: while its induction directly eliminated cancer cells, the resulting lipid peroxidation could simultaneously impair the survival and metabolic fitness of infiltrating immune cells. This dualistic effect necessitated precise, cell-type-specific strategies to ensure that ferroptosis-mediated tumor suppression did not undermine the anti-tumor immune response. Similarly, autophagy in tumor cells facilitated immune evasion via the selective degradation of major histocompatibility complex class I (MHC-I) and stabilizing programmed death-ligand 1, while it also improved the cytotoxic function and cellular longevity of natural killer cells. Consequently, future drug development should consider cell-type-specific modulation to address these contradictory effects across different cells and avoid unintended immunosuppression. Emerging evidence on PANoptosis, which integrates multiple programmed cell death pathways into a synergistic framework, may provide a useful direction for investigating immune therapeutic resistance. Ultimately, targeting the intricate landscape of programmed cell death may inform strategies for improving cancer treatment and urological immunotherapy, but stronger translational evidence is still needed.

Triple negative breast cancer (TNBC) is defined by the absence of oestrogen receptor, progesterone receptor, and HER2 expression, and carries a disproportionate burden of breast cancer-related mortality due to its aggressive biology and historically limited therapeutic options. The treatment landscape of metastatic TNBC has undergone a fundamental transformation over the past decade, driven by immune checkpoint inhibitors, antibody-drug conjugates (ADCs), and the identification of actionable genomic alterations. This review provides a comprehensive, clinically oriented appraisal of the current and emerging therapeutic landscape of metastatic TNBC, encompassing its molecular underpinnings and tumour microenvironment biology. We critically evaluate the evolving roles of immune checkpoint inhibition, ADCs, PARP inhibitors, and novel targeted approaches, discuss mechanisms of resistance and biomarker limitations, and propose a framework for rational, biomarker-guided treatment selection and sequencing to support evidence-based clinical decision-making in this rapidly evolving field.

Objective: Liposomal doxorubicin (L-DOX) may alter macrophage-mediated immune regulation in triple-negative breast cancer (TNBC), but its role in programmed death-ligand 1 (PD-L1)-associated immune escape remains unclear. This study aimed to determine whether L-DOX induces a macrophage-centered PD-L1 response and affects the efficacy of PD-L1 blockade in TNBC. Methods: Public bulk and single-cell transcriptomic datasets, bone marrow-derived macrophage models, CD8⁺ T-cell co-culture assays, promoter-binding analyses, and syngeneic EO771 and 4T1 TNBC mouse models were used to examine PD-L1 regulation and immune function after L-DOX treatment. Results: The principal findings were that L-DOX preferentially induced a PD-L1-high macrophage state and sensitized TNBC tumors to PD-L1 blockade. DOX-containing therapy was associated with PD-L1 upregulation enriched in tumor-associated macrophages, and L-DOX induced stronger macrophage PD-L1 expression than free DOX or taxane-based agents. Mechanistically, L-DOX accumulation triggered DNA damage-associated ATM-p53 and cGAS-STING signaling, leading to RELA/p65-dependent NF-κB activation and PD-L1 transcription. Functionally, L-DOX-conditioned macrophages suppressed CD8⁺ T-cell activation, proliferation, and tumor-cell killing, whereas PD-L1 blockade restored CD8⁺ effector function, promoted pro-inflammatory macrophage features, and improved tumor control in EO771 and 4T1 models compared with either monotherapy. Conclusion: L-DOX induces a PD-L1-high macrophage state with immunosuppressive features that constrains antitumor T-cell responses. Combining L-DOX with PD-L1 blockade may provide a rational chemoimmunotherapy strategy for TNBC.

To (1) examine the relationship between a single-item and multicomponent patient-reported outcome measure (PROM) for mobility; (2) identify mobility profiles (PROM-defined patterns of mobility difficulty) using these measures; and (3) explore associations between demographic or clinical characteristics and mobility profiles.

Analysis of baseline data from an ongoing multinational trial of a rehabilitation intervention for people with incurable cancer.

Oncology and palliative care outpatient services participating in an international rehabilitation trial.

A consecutive sample of 211 adults with incurable solid tumors, Eastern Cooperative Oncology Group Performance Status 2-3, and a clinician estimated prognosis of ≥3 months. Of these, 206 had complete mobility data and formed the analytic sample.

Mobility was assessed using the Integrated Palliative Care Outcome Scale (IPOS) mobility item and the World Health Organization Disability Assessment Schedule (WHODAS 2.0) mobility subdomain; higher scores reflect greater mobility limitation or difficulty. Secondary outcomes included WHODAS 2.0 self-care and participation scores and quality of life measured using the Functional Assessment of Cancer Therapy-General.

IPOS and WHODAS 2.0 mobility scores were positively correlated (ρ=0.650; 95% CI, 0.55-0.74; P<.001). Five mobility profiles were identified (Silhouette≈0.6), each defined by a single IPOS score (0-4) and WHODAS 2.0 mean scores ranging from 8.3 (SD, 3.7) to 19.3 (SD, 3.9). These groups primarily reflected a graded spectrum of mobility difficulty rather than distinct patterns. WHODAS 2.0 self-care, participation, and Functional Assessment of Cancer Therapy-General scores did not significantly differ by mobility profile. However, younger patients and those using mobility devices were represented more in mobility profiles with greater perceived mobility difficulty.

A single-item PROM identified broad functional limitations and may help identify mobility profiles among people with incurable cancer. These findings support the utility of the IPOS mobility item as a tool that may help clinicians screen for difficulties with mobility and determine when detailed assessment or rehabilitation input is warranted. The PROM-defined mobility profiles should be interpreted as exploratory stratification and not as independently validated clinical subtypes. Further studies should validate the mobility profiles' stability and clinical usefulness in longitudinal cohorts.

Primary tracheal tumors represent less than 1% of all pulmonary neoplasms, with endobronchial leiomyomas accounting for a minute fraction of benign airway lesions. Due to their slow growth and nonspecific clinical presentation, these tumors are frequently misdiagnosed as obstructive airway diseases, such as asthma. We report the case of a 27-year-old female with a 3-year history of progressive, treatment-resistant respiratory symptoms initially managed as severe asthma. Despite escalating medical therapy, her condition deteriorated, culminating in an emergency department presentation with fulminant acute respiratory failure. Chest computed tomography and subsequent rigid bronchoscopy revealed a smooth, well-encapsulated 1.9 cm pedunculated tracheal mass originating from the posterior membranous wall, causing 100% luminal obstruction. The tumor was successfully resected via bronchoscopic snare electrocautery and basket extraction, followed by argon plasma coagulation of the base. Histopathological and immunohistochemical evaluation confirmed a benign tracheal leiomyoma. Postoperatively, the patient experienced immediate, complete resolution of respiratory symptoms with no recurrence at her 3-month follow-up. Tracheal leiomyoma, though rare, can cause life-threatening central airway obstruction where timely imaging and bronchoscopic intervention are ultimately lifesaving.

Mitophagy serves as a pivotal metabolic-immune hub that drives immune evasion in major skin cancer subtypes including melanoma cutaneous squamous cell carcinoma and basal cell carcinoma. It acts as a core barrier to effective immunotherapy. Mitophagy activates canonical mitophagic pathways such as PINK1 Parkin and BNIP3 NIX. It extensively remodels the tumor immune microenvironment through multiple mechanisms. It skews tumor-associated macrophages toward immunosuppressive M2 polarization. It impairs antigen presentation of epidermal Langerhans cells. It induces exhaustion of CD8⁺ cytotoxic T lymphocytes. It also modulates pro-inflammatory cytokines including IL-1β and TNF-α. Mitophagy triggers sequential activation of NF-κB NLRP3 inflammasome and cGAS-STING signaling at the same time. It couples metabolic reprogramming and epigenetic modifications to sustain immunosuppression. A skin-cancer-specific UV-microphthalmia-associated transcription factor (MITF) regulatory axis mediates the crosstalk between mitophagy and PD-L1 expression. It generates heterogeneous and subtype-specific immune microenvironments. It further promotes resistance to immune checkpoint blockade. Mitophagy also modulates tumor antigen presentation immune checkpoint profiles and metabolic fitness of infiltrating immune cells to amplify immune evasion. This narrative review systematically delineates the multidimensional regulatory networks of mitophagy-driven immune evasion in skin cancer. It clarifies context-dependent regulatory patterns across distinct histological subtypes. It proposes precision-targeted therapeutic strategies by combining mitophagy modulation with immunotherapy. These insights provide novel mechanistic frameworks and translational targets to overcome immunotherapy resistance. They also help improve clinical outcomes for patients with advanced skin cancer.

T-cell engagers and engineered cell therapies have yet to deliver the same spectacular results in acute myeloid leukemia (AML) that they have in other hematologic malignancies. In this review, we analyze the challenges with AML immunotherapy development, including on-target, off-tumor toxicity, cytokine release syndrome (CRS), and the "myeloid sink." We then discuss the emergence of two technologies that could address the major challenges with investigational AML therapeutics: targeted, lipid nanoparticles (LNPs) loaded with specific mRNAs and a type of synthetic logic gate (a NOT gate). This approach builds on recent advancements of mRNA-loaded LNPs that developed with the COVID19 vaccines and evolved into vehicles for delivery to T cells. The LNP modality offers a new opportunity for effective treatment of patients with AML.