Exercise improves physical function and health-related quality of life (HRQoL) in patients with cancer; however, nationwide structured programmes remain limited. A hospital in Germany implemented a donation-funded Haematological and Oncological Training Therapy with Stationary Strength and Cardio Machines (HOT), and a 3-year real-world data analysis aimed to evaluate its acceptance, feasibility, safety, and effects.

Endometrial cancer (EC) incidence continues to rise, underscoring the need for effective therapies beyond BRCA-mutant disease. Although PTEN loss, a frequent alteration in EC, has been implicated in impaired homologous recombination and increased sensitivity to PARP inhibitors, responses to PARP inhibitor monotherapy remain variable and are often limited by resistance mechanisms in PTEN-deficient tumours. Here, we show that the dual PARP/tankyrase (TNKS) inhibitor JPI-547 exerts potent antitumor activity, particularly in PTEN-deficient Ishikawa tumours. In vitro, JPI-547 and olaparib more effectively reduced cell survival in PTEN-deficient cells, and combined treatment with olaparib and the TNKS inhibitor XAV-939 induced synergistic cytotoxicity with elevated DNA double-strand breaks. Dual PARP/TNKS inhibition did not further suppress RAD51 but modulated non-homologous end joining and attenuated Wnt/β-catenin signalling in a PTEN-dependent manner. PTEN knockdown further showed enhanced vulnerability to combined targeting. These findings show that JPI-547 enhances antitumor efficacy in PTEN-deficient EC by disrupting DNA repair pathways and Wnt signalling, supporting dual PARP/TNKS inhibition as a potential therapeutic strategy and providing a rationale for further clinical evaluation.

Immune checkpoint inhibitor-induced immune-related adverse events (irAEs) can be steroid-refractory (sr) or steroid-dependent (sd), requiring second-line therapy. Evidence guiding optimal management of sr/sd-irAEs while preserving antitumor efficacy is scarce. This study compared extracorporeal photopheresis (ECP) with systemic immunosuppressants (IS) for treatment of sr/sd-irAEs.

Anti-PD-1 monoclonal antibody (mAb) therapy promotes the emergence of new T cell clonotypes within tumors, suggesting de novo priming in the periphery. Yet, the mechanisms that mobilize these additional T cells remain poorly defined.

Due to the heterogeneity in cancer patients, accurate prediction of cancer drug response is key to achieving personalized medicine. The biological differences between cell lines and tumor tissues, as well as the domain shift caused by diverse drug mechanisms of action, make it difficult for existing methods to effectively capture the complex relationships between multimodal features. In this study, we propose a multimodal feature fusion and feature disentanglement model, named MDCDR. The model effectively integrates various modalities of drugs and cell lines. By employing an interaction-level feature disentanglement framework that integrates multi-granularity contrastive learning and feature masking prediction, we successfully achieve effective synergy between shared common patterns and specific preserved patterns at the drug-cell line interaction level. Experiments show that MDCDR significantly outperforms existing methods on benchmarks and independent clinical test sets, and exhibits good generalization to new cell lines and drugs. Furthermore, case studies on Acute Myeloid Leukemia demonstrate MDCDR's capacity to elucidate pathway-drug associations, offering biologically interpretable guidance for precision treatment.

The liver is central to drug metabolism and a critical site of disease progression, making vascularized in vitro liver models essential for disease modeling, drug discovery, and mechanistic research. However, recapitulating dynamic in vivo drug responses while maintaining clinical relevance remains a major challenge for bioartificial liver systems. In acute myeloid leukemia (AML), patients frequently develop leukemic liver infiltration and chemotherapy-induced hepatotoxicity, both of which compromise therapeutic efficacy and prognosis. Human-relevant experimental models that dynamically simulate these processes are urgently needed. Here, we developed a dynamic perfusable human vascularized liver module (DPHV-LM), constructed from in vitro-expanded primary human hepatocytes within a perfusable scaffold. Perfusion of AML patient-derived cells reproduced leukemic infiltration of liver tissue. Using the DPHV-LM for drug screening and validating findings in AML mouse models, we identified ammonium glycyrrhizinate (AMGZ) as an agent that reduces cytarabine-induced hepatotoxicity and suppresses leukemic infiltration without impairing antileukemic efficacy. The hepatoprotective trends observed in the DPHV-LM were qualitatively concordant with findings from an independent retrospective clinical cohort. Collectively, these results demonstrate the transplantational potential of this platform for modeling leukemic liver pathology and for the development of hepatoprotective therapeutic strategies.

Urolithin C (UC), a natural compound derived from the metabolism of ellagitannins by gut microbiota, exhibits diverse pharmacological and biological activities. However, its therapeutic potential and underlying mechanisms in endometrial cancer (EC) remain unclear. Functional assays were used to determine the effects of UC on the viability, proliferation, cell cycle, apoptosis, migration, and autophagy in EC cells. RNA sequencing was used to investigate the effect of UC on total gene expression in EC cells. The expression level of activating transcription factor 3 (ATF3) was evaluated using western blotting, real-time PCR, and immunofluorescence staining. Organoids and a mouse model of EC were used to analyze the anti-tumor effects of UC. UC significantly inhibited the malignant behavior of EC cells. High-throughput transcriptome sequencing revealed a close association between autophagy and UC treatment, and identified ATF3 as a key downstream factor. UC treatment increased the expression of ATF3, which was primarily localized to the nucleus. Elevated ATF3 levels positively correlated with the survival of patients with EC. ATF3 knockdown rescued the effects of UC on cell viability, migration, and autophagy. Furthermore, EC organoid and in vivo experiments showed that UC markedly reduced organoid viability and EC tumor growth. UC exerts anti-EC activity by promoting ATF3 expression, thereby inhibiting the malignant behavior of EC cells and promoting autophagic cell death.

Poly(ADP-ribose) polymerases (PARPs) have emerged as pivotal therapeutic targets due to their essential function in DNA single-strand break repair, particularly in cancers with BRCA1/2 mutations. Although PARP inhibitors show promising clinical responses, their long-term efficacy is often compromised by the development of drug resistance, which limits sustained therapeutic success. To address this, identifying molecules capable of modulating additional cancer-relevant pathways has become an emerging strategy. G-quadruplexes (G4s), enriched in oncogenic promoter regions, have gained considerable attention as therapeutic targets. In this study, we investigated the ability of two PARP inhibitors, PARP inhibitor VIII (PI VIII) and PARP inhibitor XI (PI XI), to bind and stabilize G4 structures using biophysical assays and molecular docking. Our results reveal that PI VIII exhibits a markedly stronger affinity for G4 structures compared to PI XI, with a preference for the G4 motif present in the c-myc oncogene, which is frequently overexpressed in cancer cells. Moreover, PI VIII demonstrates enhanced binding and stabilization of the c-myc G4 relative to duplex DNA. The observed stabilizing effect involves electrostatic interactions, hydrogen bonding, and π-π stacking. These findings identify PI VIII as a promising dual-mode anticancer candidate capable of simultaneously inhibiting PARP activity and stabilizing oncogenic G-quadruplexes.

Platinum(II)-based photoactivatable anticancer agents that combine chemotherapy and photodynamic therapy (PDT) represent a promising strategy to overcome resistance and systemic toxicity of classical platinum drugs. Herein, we report a density functional theory (DFT) and time-dependent DFT investigation of dipicolylamine (dpa)-based monofunctional Pt(II) complexes conjugated to boron dipyrromethene (BODIPY) chromophores. Starting from two experimentally characterized systems, we designed new Pt-BODIPY architectures aimed at shifting light absorption into the therapeutic window (600-850 nm) while preserving platinum reactivity toward DNA. The results demonstrate that extension of π-conjugation and appropriate linker engineering effectively redshift the absorption maximum up to 661 nm without compromising capability of singlet oxygen generation. All conjugates exhibit triplet energies (1.03-1.57 eV) sufficient to sensitize molecular oxygen and calculated intersystem crossing (ISC) rates typical of chromophore-dominated systems, with limited spin-orbit coupling (SOC) enhancement from the Pt center. Mechanistic analysis of aquation and guanine coordination shows activation barriers and thermodynamics comparable to conventional Pt(II) drugs, indicating that chromophore conjugation does not hinder DNA platination. Overall, this study provides structure-property relationships and rational guidelines for the development of dual-action Pt-BODIPY chemo-photodynamic agents.

Qualitative liquid chromatography-mass spectrometry (UHPLC-MS) and NMR analysis of the diethyl ether extract of the aerial part of Eryngium dichotomum plant belonging to the Apiaceae family led to the putative identification of phenolic acids, flavonoid glycosides, triterpenoid saponins, fatty acids, and oxylipins. The tentative identification of several secondary metabolites by UHPLC-MS analysis was further confirmed by compound isolation and comprehensive spectroscopic characterization using 2D NMR and mass spectrometry, leading to the elucidation of seven compounds, a mixture of two hydroxy fatty acids, namely (Z,E)-13-hydroxyoctadeca-9,11-dienoic acid (1) and (E)-13-hydroxyoctadec-11-enoic acid (2); two C17 polyacetylenes, (E)-heptadeca-1,10-dien-4,6-diyne-3,8,9-triol (3), and falcarinol ((Z)-1,9-heptadeca-1,9-dien-4,6-diyn-3-ol) (4); glycerol monopalmitate (5) and two flavonoid glycosides, kaempferol 3-O-β-D-glucopyranosyl-(1 → 6)-O-β-D-galactopyranoside (6), and quercetin 3-O-β-D-glucopyranosyl-(1 → 6)-O-β-D-galactopyranoside (7). Furthermore, the antioxidant activity of the n-butanol and the diethyl ether extracts of the species were evaluated using the DPPH, FRAP, and ABTS assays. In addition, the anticancer activity of the major falcarinol-type polyacetylene was assessed against A375 human melanoma cells.

Cancer remains a leading cause of death worldwide, and while various therapeutic strategies exist for its treatment, many have limited efficacy and significant adverse effects. Given this situation, there is a need to identify more effective and less aggressive therapeutic alternatives. In this context, natural products have garnered significant interest due to their potential as anticancer agents. This review aims to highlight the nutraceutical potential of edible plants belonging to the Cucurbitaceae, Brassicaceae, Liliaceae, and Chenopodiaceae families, evaluated in different tumor cell lines, as several studies have extensively demonstrated their antitumor activity and their potential application in cancer prevention and treatment.

Background: Cancer remains a major global health challenge, with treatment efficacy often limited by drug resistance and adverse effects. Drug repurposing offers promising opportunities for developing novel anticancer strategies. This study evaluated the cytotoxic, antiproliferative, and pro-apoptotic effects of metformin and caffeine, administered individually and in combination, in human cancer cell lines, as well as their potential interaction mechanisms. Methods: Human cervical carcinoma (HeLa), lung adenocarcinoma (A549), and colorectal carcinoma (HT29) cell lines were treated with metformin (0.05-50 mM) and caffeine (0.5-5 mM), either alone or in combination, for 24 and 48 h. Cell viability and proliferation were assessed using Trypan Blue and sulforhodamine B (SRB) assays. Apoptosis was analyzed by Annexin V/propidium iodide flow cytometry, and p53 expression in HeLa cells was determined by ELISA. Statistical analysis was performed using a one-way ANOVA followed by Tukey's post hoc test. Results: Metformin induced dose- and time-dependent cytotoxicity in all tested cell lines, with the lowest IC50 values observed in HeLa and A549 cells after 48 h (2.28 and 3.30 mM, respectively; p < 0.05). Caffeine showed moderate antiproliferative activity, with the strongest effects observed at 2.03 mM in HeLa cells and 2.01 mM in HT29 cells (p < 0.05). The combined treatment produced effects that varied depending on both the cell line and exposure time. At earlier time points, transient synergistic effects were observed in certain cell lines, particularly HeLa cells; however, these effects were not sustained over time. With prolonged exposure, the interaction shifted predominantly toward antagonistic effects, indicating the reduced overall efficacy of the combination compared with the expected additive outcomes. Increased apoptosis and elevated p53 expression further supported the activation of tumor-suppressive pathways. Conclusions: Metformin exhibited significant anticancer activity in vitro, supporting its potential repurposing in oncology. However, the addition of caffeine did not uniformly enhance its efficacy and appeared to exert context-dependent effects. Further in vivo studies are required to confirm the clinical relevance of these findings.

The shortage of effective chemotherapeutic agents poses a significant challenge to the global public health system. Cancer is among the leading diseases affecting the human population worldwide. Issues such as drug resistance, toxicity, lack of specificity, poor bioavailability and water solubility, and severe side effects reduce the effectiveness of many existing anticancer drugs. As a result, there is growing interest in discovering a new generation of therapeutic agents to overcome these limitations. Phenolic acids, including ferulic and caffeic acids, are cinnamic acid derivatives with numerous biological effects, including anti-inflammatory, antibacterial, antifungal, antioxidant, antiviral, cytotoxic, and antiproliferative effects. In recent years, drug repurposing and hybridization strategies have emerged as attractive approaches in medicinal chemistry because they may reduce both the cost and time associated with conventional drug discovery. As a result, several researchers have combined ferulic acid and caffeic acid scaffolds with different pharmacophores to generate hybrid compounds with enhanced anticancer potential. This review summarizes recent in vitro and in silico studies published between 2022 and 2025 on ferulic and caffeic acid hybrid compounds that exhibit cytotoxic and antiproliferative effects. Furthermore, the review discusses structure-activity relationship trends, synthetic approaches, and structural modifications associated with improved biological activity. Collectively, the findings highlight the significant potential of ferulic acid and caffeic acid scaffolds in the development of multifunctional anticancer agents.

Reactive oxygen species (ROS)-mediated cancer therapy has attracted extensive attention due to its high spatiotemporal selectivity and minimal side effects. Herein, we report a nonanuclear Pd-based coordination cage of Pd6-TMPP(Ni), constructed from Ni-chelated TMPP(Ni) as the metalloligand and Pd2+ ions (H2TMPP = meso-tetrakis (6-methylpyridin-3-yl) porphyrin). Pd6-TMPP(Ni) integrates dual ROS-generation for cancer therapy, viz., hydroxyl radical (•OH) production and photoinduced singlet oxygen (1O2) generation. In vitro cytotoxicity assays against cancer cell lines NCI-H82 (lung cancer), A549 (lung cancer), KYSE-510 (esophageal cancer), and Te-1 (esophageal cancer) reveal its potent dark toxicity (IC50: 1.9-2.1 μmol L-1) and phototoxicity (IC50: 0.8-1.5 μmol L-1), which is attributed to enhanced intracellular ROS accumulation. This work develops a versatile therapeutic platform that harnesses Ni-induced •OH for chemodynamic therapy (CDT) and porphyrin-generated 1O2 for photodynamic therapy (PDT), thereby mitigating the oxygen dependence of conventional PDT.

EML4-ALK-positive lung cancer represents an important molecular subtype of non-small-cell lung cancer (NSCLC) that initially responds to ALK inhibitors but invariably develops resistance, highlighting the need for novel targeted therapeutic strategies. Death receptors DR4 and DR5 are frequently upregulated in malignancies and can selectively induce tumor cell apoptosis upon binding TRAIL. ISZ-sTRAIL, a trimer-stabilized soluble TRAIL fusion protein, exhibits potent antitumor effects via DR4/DR5 signaling activation. However, the expression status of DR4/DR5 in EML4-ALK-positive NSCLC cells and the therapeutic potential of targeting this pathway remain poorly defined. In this study, we evaluated DR4/DR5 protein expression in EML4-ALK-positive NSCLC cells and investigated the antitumor effect of ISZ-sTRAIL produced in an Escherichia coli expression system. Our results showed that DR4 and DR5 were abundantly expressed in EML4-ALK-positive NCI-H2228 and NCI-H3122 cells compared with normal human bronchial epithelial 16HBE cells. Furthermore, ISZ-sTRAIL significantly suppressed the proliferation of NCI-H2228 and NCI-H3122 cells, with IC50 values of 4.51 ± 0.22 nM and 14.98 ± 3.34 nM, respectively, while showing low cytotoxicity toward normal 16HBE cells (IC50 > 1 μM). Moreover, ISZ-sTRAIL induced caspase-dependent apoptosis in both cell lines via activation of extrinsic and intrinsic pathway, and these effects were markedly abrogated by the pan-caspase inhibitor Z-VAD. These findings identify DR4/DR5 as a potential therapeutic target and provide preclinical evidence for the development of TRAIL-based strategies in the treatment of EML4-ALK-positive NSCLC.

This work focuses on rapid, catalyst-free synthesis of a new series of acetylenic phosphonates as promising building blocks for creating antiviral and anticancer agents. A comprehensive assessment of the biological activity of the synthesized compounds was conducted. Dialkyl phosphonates 4d, 4e, and 4g were found to exhibit pronounced antiproliferative activity against human cancer cell lines, with the greatest IC50 = 6 μg/mL against the K562 cell line. Further studies revealed that these compounds cause significant disorganization of the actin cytoskeleton, leading to the loss of stress fibers and reduced cell motility. In contrast, diamide derivatives demonstrated a more favorable safety profile, with low cytotoxicity and moderate antiviral activity against influenza A (H1N1) virus, among which compound 6b achieved a selectivity index of 5 with IC50 = 56.9 μg/mL. Screening studies of both dialkyl and diamide acetylenic phosphonates revealed some features of the interaction with kinase and nonkinase targets used for drug development and provide a basis for the subsequent rational design of novel selective anticancer agents based on the acetylenic phosphonate scaffold.

Fatty acids (FAs) have drawn attention in the field of oncology due to their multifaceted role, not only as structural components of lipid-based delivery systems but also as functional moieties that can enhance the pharmacokinetic and biological behavior of anticancer drugs and, subsequently, their therapeutic performance. Due to their biocompatibility, structural diversity, high affinity for biological membranes, and albumin-binding capacity, FAs can increase drug lipophilicity, membrane permeability, systemic distribution, tissue distribution, and enable controlled enzymatic release. All these properties endorse the development of nanocarriers containing FAs, such as liposomes, lipid nanoparticles (LNPs), self-nanoemulsifying drug delivery systems (SNEDDS), and self-assembling lipidic prodrugs (LAPs). In addition, several FAs, especially polyunsaturated FAs, seem to have a direct anticancer activity by modulating lipid metabolism, oxidative stress, membrane organization, and regulating cell death pathways. This review summarizes the FA conjugation chemistry, the influence of FA on the pharmacokinetics and tumor-targeting capacity of anticancer agents, and the current developments in FA-based cancer treatment strategies, while also covering the biological functions of FA in cell death pathways and cancer metabolism. By integrating medicinal chemistry, nanocarrier design, pharmacokinetic modulation, and tumor lipid biology, this review positions FA-based strategies as a relevant and evolving platform for improving anticancer drug delivery, tumor selectivity, and therapeutic performance.

Ascorbic acid plays an important role in the human body due to its antioxidant and anti-inflammatory properties, as well as its involvement in collagen synthesis, enzymatic regulation, and the biosynthesis of corticosteroids and selected neurotransmitters. Owing to these diverse functions, it is used both in the prevention and supportive treatment of several disorders and as a mild, non-toxic reducing agent in the synthesis of gold nanoparticles (AuNPs). In the present study, a method for synthesizing gold nanoparticles was developed using second-generation poly(amidoamine) dendrimers (PAMAM G2) with an ethylenediamine core as stabilizing agents and ascorbic acid as the reducing agent. The synthesis was performed using two techniques: sonication and microwave irradiation. A comparative analysis was conducted for colloidal systems obtained at various molar ratios of PAMAM G2 dendrimers to chloroauric acid (ranging from 1:1 to 1:5). The presence of gold nanoparticles was confirmed using ultraviolet-visible spectroscopy (UV-Vis). Nanoparticle diameters and zeta potentials were determined by dynamic light scattering (DLS). The sizes of the metallic cores were estimated using scanning transmission electron microscopy (STEM). Furthermore, the morphology and topography of entire complexes deposited on silicon substrates were visualized using atomic force microscopy (AFM). For cytotoxicity studies on human breast adenocarcinoma and human osteosarcoma cell lines, the most stable colloids-those obtained at a PAMAM G2:HAuCl4 molar ratio of 1:3-were selected. Results indicate that the synthesized nanoparticles exhibit slightly higher cytotoxicity compared with AuNPs/PAMAM G2 complexes reduced with sodium citrate, as evidenced by lower EC50 values (the concentration responsible for reducing cell viability to 50%). It should be emphasized, however, that AuNPs/PAMAM G2 reduced with ascorbic acid are significantly smaller, with diameters of approximately 10 nm, whereas citrate-reduced nanoparticles exhibit diameters of around 20 nm. These results indicate that nanoparticle size, rather than the chemical nature of the reducing agent, is a dominant factor governing the cytotoxic response of AuNPs/PAMAM G2 complexes.

T-cell acute lymphoblastic leukemia (T-ALL) remains a challenging malignancy with limited targeted therapies. Natural phenanthrene derivatives represent a promising source of antileukemic agents.

Chemotherapy-induced cognitive impairment (CICI), often referred to as "chemobrain," is a common and sometimes persistent consequence of cancer treatment, characterized by deficits in memory, attention, executive function, and processing speed; it disproportionately affects older adults and women, suggesting a role for aging- and sex-related biological factors, including estrogen depletion. This work examines the potential of dietary phenolic compounds as multi-target modulators of mechanisms underlying CICI. A narrative synthesis of preclinical and clinical evidence was conducted, focusing on major phenolic subclasses (flavonoids, phenolic acids, stilbenes, lignans, and secoiridoids) and their effects on pathways implicated in chemotherapy-related neurotoxicity. The reviewed data indicate that phenolic compounds can influence redox balance, neuroinflammatory responses, mitochondrial function, synaptic plasticity, and estrogen-related signaling, with effects that appear to be structure-dependent; however, evidence remains heterogeneous and largely derived from experimental models rather than studies in humans. Overall, the current findings suggest that selected phenolic compounds could mitigate vulnerability to CICI, particularly in higher risk groups such as older individuals and women with low estrogen levels. These compounds represent promising and safe adjunctive strategies, although further well-designed clinical studies are needed to confirm their efficacy and clarify the underlying mechanisms.