Prostate cancer remains a major cause of cancer-related mortality, and new therapeutic strategies are needed for advanced disease. Niclosamide and related salicylanilide compounds have emerged as multitarget anticancer agents, but the molecular contexts associated with their activity remain incompletely understood. Here, we applied a phenotype-oriented integrative framework to characterize the molecular context and phenotypic activity of NSC828786, a niclosamide-like salicylanilide derivative. Cross-cohort transcriptomic analyses identified AMACR (alpha-methylacyl-CoA racemase) and HPN (hepsin) as consistently upregulated genes in independent prostate adenocarcinoma cohorts. NCI-60 profiling demonstrated broad-spectrum low-micromolar antiproliferative activity, including AR-negative prostate cancer and breast cancer cell lines spanning multiple receptor subtypes; however, quantitative ranking did not support preferential receptor subtype selectivity. CellMiner COMPARE analysis showed no significant correlation between baseline AMACR or HPN expression and NSC828786 sensitivity. Structure-based analyses supported computational compatibility of NSC828786 with predicted HPN- and AMACR-associated binding regions, while zebrafish assays showed no overt developmental abnormalities at concentrations ≤ 5 μM. These findings identify NSC828786 as a phenotypically active salicylanilide derivative and position HPN and AMACR as exploratory candidate molecular associations warranting further mechanistic and target engagement studies.

Triple-negative breast cancer (TNBC) is characterized by a lack of estrogen, progesterone, and HER2 receptors; an aggressive phenotype; high rates of early relapse and metastasis; and the worst mortality rates among all breast cancer subtypes. Currently, there is no effective curative targeted therapy for TNBC and chemotherapy remains the primary treatment for TNBC. Therefore, there is a critical need to develop highly effective, novel therapies to improve patient survival. We previously validated FOXM1, a proto-oncogenic transcription factor, for the first time as a potential molecular target in TNBC through genetic knockdown studies in mice. We show that FOXM1 expression is associated with shorter patient survival and is a marker of poor prognosis. There is no FDA-approved FOXM1 inhibitor. We found that patients with TP53 mutations have dramatically higher FOXM1 expression, indicating that widespread TP53 mutations detected in about 80% of TNBC patients are the major driver of FOXM1 overexpression in TNBC patients. We identified its binding ability using an in silico study, and found it to be a well-known FOXM1 inhibitor that suppresses TNBC cell proliferation, migration, and invasion, and induces apoptosis. In vivo studies in mice bearing TNBC tumors demonstrated that treatment with a novel FOXM1 inhibitor incorporated in single-lipid nanoparticles suppressed the growth of TNBC tumor xenografts. In conclusion, our findings suggest that the novel FOXM1 inhibitor represents a potent and safe therapeutic strategy with significant potential for the treatment of other FOXM1-driven cancers including TNBC that currently have limited treatment options.

Opioids are frequently prescribed for cancer pain management, yet accumulating evidence suggests that opioid exposure may be associated with inferior outcomes in patients also undergoing treatment with immune checkpoint inhibitors (ICIs). To synthesize mechanistic and clinical evidence linking opioids to the PD-1/PD-L1 axis, the literature was searched up to 18 January 2026, with study selection and data extraction focused on (i) cancer-cell and immune-cell effects of opioid agonism or antagonism on PD-1/PD-L1 biology, and (ii) clinical studies reporting ICI outcomes (progression-free survival, overall survival, or treatment duration) with concomitant opioid exposure. Preclinical studies support multiple, non-mutually exclusive mechanisms: opioids can induce PD-L1 in tumour cells, modulate innate-inflammatory pathways (including TLR4-linked cascades), promote dysfunctional T-cell phenotypes that reduce responsiveness to PD-1 blockade, and show context- and opioid-dependent effects. Clinical cohorts and meta-analytic datasets in non-small cell lung cancer and other tumour types report associations between opioid exposure (including higher morphine-equivalent dosing) and worse ICI outcomes. The intersection of opioid signaling with PD-1/PD-L1 biology likely operates across cancer cell-intrinsic and immune cell-intrinsic pathways, providing a mechanistic rationale for prospective evaluation of opioid-sparing strategies and/or peripheral opioid antagonism as adjuncts to checkpoint blockade.

Chemotherapy-induced nausea and vomiting substantially impair patients' quality of life despite considerable advances in supportive care. Neurokinin-1 receptor antagonists, including oral aprepitant and intravenous fosaprepitant, constitute essential components of antiemetic regimens for highly emetogenic chemotherapy. In this prospective, non-randomized observational study, we compared the efficacy of oral aprepitant and intravenous fosaprepitant administered in combination with 5-hydroxytryptamine-3 receptor antagonists and dexamethasone in 136 chemotherapy-naive patients receiving cisplatin- or doxorubicin-cyclophosphamide-based regimens. Complete response rates during the acute (0-24 h), delayed (24-120 h), and overall (0-120 h) phases were comparable between the two groups, with no statistically significant differences in emesis severity. Multivariable analyses further demonstrated similar effectiveness irrespective of age, sex, or chemotherapy regimen. These findings indicate that no statistically significant differences in antiemetic efficacy were observed between aprepitant and fosaprepitant in routine clinical practice. Fosaprepitant may therefore represent a practical alternative when oral administration is not feasible.

Immune checkpoint inhibitors (ICIs) are widely used in advanced non-small cell lung cancer (NSCLC) but can lead to immune-related adverse events (irAEs) that may disrupt care. Although irAEs are well described clinically, there is limited evidence quantifying their downstream health care use and costs in Medicare beneficiaries with advanced NSCLC.

Goniothalamin (GTN), a natural styryl-lactone from the Goniothalamus genus, has demonstrated cytotoxic properties against a variety of human cancer cell lines with minimal effects on normal cells. Its traditional medicinal use and preliminary preclinical evidence suggest potential as a selective anticancer agent. The purpose of this review is to summarize the preclinical anticancer activity, molecular mechanisms, and therapeutic potential of GTN and its semi-synthetic derivatives across cancer cell lines and animal models. A comprehensive literature search was conducted on the anticancer effects of GTN using databases including PubMed, Scopus, and ScienceDirect. Studies reporting in-vitro cytotoxicity, half-maximal inhibitory concentration (IC50) values, mechanisms of action, synergistic drug effects, and in-vivo antitumor efficacy were included. Data on GTN enantiomers and semisynthetic derivatives were also analyzed. GTN exhibited potent, dose- and time-dependent cytotoxicity in breast, colorectal, hepatoma, leukemia, and other cancer cell lines (IC50 in the low micromolar range), while sparing normal cells. Mechanistically, GTN induced DNA damage, reactive oxygen species (ROS) generation, cell cycle arrest, endoplasmic reticulum stress, apoptosis, autophagy, necroptosis, and anoikis. The anticancer activity of GTN enantiomers appears to be cell-line dependent: although the (R)-enantiomer showed higher potency in several cancer models, the (S)-enantiomer displayed greater activity in selected cancer cell lines. GTN synergized with chemotherapeutics such as paclitaxel, vinblastine, and cisplatin, enhancing apoptosis and reducing cell viability. Semi-synthetic derivatives, including methoxy- and nitro-substituted analogs, demonstrated enhanced potency and selectivity. In animal models, GTN exhibited antitumor activity without detectable toxicity. GTN is a promising natural anticancer agent with multimodal mechanisms of action and selective cytotoxicity. Semisynthetic derivatives further improve its potency and specificity. Further in-vivo studies, bioavailability, and pharmacokinetic investigations are warranted to advance GTN towards clinical application.

The cyclic GMP-AMP (cGAS) synthase and stimulator of interferon genes signaling pathway plays a central role in bridging innate and adaptive immunity, particularly within the context of cancer. Activation begins when cytosolic double-stranded DNA is detected, leading to the production of cyclic GMP-AMP (cGAMP) and subsequent activation of STING. This initiates a cascade that induces the expression of type I interferons (IFN) and proinflammatory cytokines, enhancing antitumor immune responses through the stimulation of dendritic cells, cytotoxic T lymphocytes, and natural killer cells. Despite strong therapeutic potential, many currently available cyclic dinucleotide (CDN) and synthetic noncyclic dinucleotide (non-CDN) STING agonists face critical limitations. Common issues include poor pharmacokinetics, low cellular permeability, enzymatic degradation, and inadequate systemic bioavailability. In some cases, excessive immune activation has been observed, resulting in toxicity, chronic inflammation, or immunosuppressive tumor microenvironments. Furthermore, species-specific activity restricts the translational relevance of several compounds. These limitations highlight the need for the development of novel STING agonists with improved potency, selectivity, safety, and pharmacological profiles. This review presents a detailed analysis of molecular design approaches and structure-activity relationship (SAR) data for STING agonists, emphasizing their relevance in cancer therapy. A total of 60 synthetic compounds with diverse chemical scaffolds are examined to identify structural features linked to enhanced STING activation. These findings may support the discovery of novel STING-targeted molecules that could improve therapeutic outcomes in cancer treatment.

Immune checkpoint inhibitors (ICIs), such as PD-1/PD-L1 inhibitors, have revolutionized the treatment of extensive-stage small-cell lung cancer (ES-SCLC). Chemotherapy combined with PD-1 or PD-L1 inhibitors has become the standard first-line treatment for ES-SCLC. However, with the broad application of immunotherapy, adverse events associated with this therapy have been increasingly reported by clinicians. The identification of atypical and specific manifestations of immune-related adverse events (irAEs) requires accumulated experience on the part of clinicians. In this article, we report the case of a patient over 50 years of age who was initially diagnosed with ES-SCLC. Clinical symptoms mainly manifested as allodynia of the abdominal wall following PD-L1 inhibition immunotherapy. This symptom progressed with continued immunotherapy and resolved after cessation of immunization and treatment with prednisone. A peripheral neuropathy antibody test revealed anti-GM4 IgG antibody positivity. On the basis of the patient's clinical manifestations and medication history described above, a diagnosis of immune-related peripheral neuropathy was made. In this case, the irAE severely hindered the treatment process and impaired the patient's quality of life. Through this case report and a review of the literature, we aim to explore how to timely and accurately identify irAEs in immunotherapy, especially nonspecific irAEs, and provide timely treatment to improve patient quality of life and survival and immunotherapy precision and safety.

A previously unknown lignan, methyl-(7S, 8S)-4-hydroxy-4',7-epoxy-8,3'-neolignan-7'-ate (MEHN), was isolated from an extract prepared from the pooled stems and leaves of Conocarpus lancifolius and structurally elucidated using comprehensive spectroscopic analysis and ECD calculations. The compound revealed prominent antiradical activity in both ABTS (IC50 = 18.90 ± 1.85 µM) and DPPH (IC50 = 36.95 ± 2.47 µM) assays, relative to the reference antioxidant ascorbic acid. In an MTT colorimetric assay, MEHN at various concentrations (1.562-200 µM) exerted pronounced cytotoxic effects against HepG2 (IC50 = 14.30 ± 2.70 µM) and MCF-7 (IC50 = 20.81 ± 1.34 µM) cells, while showing weak cytotoxicity against HCT-116, H1299, H522, and non-malignant cell line MCF-10A (IC50 > 100 µM), indicating selective activity against specific cancer cell lines when compared with the standard chemotherapeutic agent 5-fluorouracil. Its computational ADMET evaluation showed favorable pharmacokinetic behavior, compliance with drug-likeness criteria, and low predicted toxicity. Overall, the newly isolated lignan sheds light on the chemical diversity of C. lancifolius with multifunctional biological activities, suggesting its potential relevance for further chemical and pharmacological research.

The genus Eugenia comprises approximately 1050 species widely used in traditional medicine and human nutrition due to their diverse pharmacological properties. This review aimed to critically summarize the anticancer potential of Eugenia species and to correlate their biological activities with the presence of bioactive phytochemicals. Literature published between 2013 and 2025 was retrieved from PubMed, SciELO, and Google Scholar databases using terms related to Eugenia, cancer, antiproliferative, and cytotoxic activities. Increasing evidence has demonstrated the anticancer effects of selected Eugenia species in in silico, in vitro, and in vivo models against different cancer types. These effects are associated with multiple mechanisms, including apoptosis induction via caspase-3/7 activation and Fas receptor upregulation, inhibition of tumor cell migration and invasion through suppression of MMP-2 and MMP-9, and cell cycle arrest. The observed activities are closely related to the presence of flavonoids, phenolic acids, carotenoids, monoterpenes, triterpenes, and sesquiterpenes. Despite promising preclinical findings, limitations such as the scarcity of in vivo studies, lack of extract standardization, and absence of clinical trials still hinder the translational application of Eugenia-derived compounds in oncology. Future studies focusing on mechanistic elucidation, bioavailability, toxicity, and clinical validation are essential for the development of Eugenia-based anticancer therapies.

Multiple myeloma (MM) is a hematological malignancy with limited therapeutic options. Drug repurposing offers a pragmatic strategy to identify novel candidates, including those from Traditional Chinese Medicine (TCM). Here, a gene signature-guided repurposing approach was applied to transcriptomic data using Limma and weighted gene coexpression network analysis to define MM-associated hub genes, followed by diagnostic and prognostic evaluation. Coremine Medical screening identified Camellia sinensis root (CSR) and Ginkgo biloba leaves (GBL) as promising candidates. CSR and GBL extracts inhibited MM cell proliferation with IC50 values of 1.54 mg/mL and 1.79 mg/mL, respectively, and induced G2/M cell cycle arrest with cyclin B1 downregulation. Apoptosis assays showed increased cell death and Bcl-2/Bax modulation. Wnt/β-catenin signaling was suppressed, correlating with cell cycle arrest and apoptosis. HPLC analysis revealed that CSR is rich in amino acids and flavanols, including L-theanine and epicatechin, while GBL contains flavonol glycosides and terpene lactones, such as quercetin, kaempferol, isorhamnetin, ginkgolide A-C, and bilobalide. These results indicate that CSR and GBL exert selective anti-myeloma activity via Wnt/β-catenin-mediated cell cycle arrest and apoptosis, highlighting their potential as repurposing candidates for MM.

The development of new therapeutic agents for glioblastoma and hepatocellular carcinoma (HCC) remains a priority due to poor prognosis, limited treatment options, and high recurrence rates. Herein, we report a one-pot synthesis of aromatic aminopropyl lactams (ArAPLs) via hydrolysis of bicyclic amidines (DBN, DBU), followed by reductive amination with aromatic aldehydes. These compounds were designed to target histamine H3 receptors (H3R), which are often overexpressed in these malignancies. Docking studies suggested that compounds 3a and 4a may act as H3R antagonists, showing favorable binding through hydrophobic and hydrogen-bonding interactions. Biological evaluation identified 3a and 4a as the most promising compounds, exhibiting micromolar antiproliferative activity in glioblastoma and HCC cell models. Compound 3a showed the best balance between potency and selectivity, including activity in 3D spheroid models and modulation of cell cycle-related markers. In coculture systems, spheroids displayed reduced size and density, although a slight increase in viability was observed, particularly with 4a. Variations in peripheral cell layers suggest a role for macrophage behavior. Overall, these findings support the cytotoxic potential of ArAPLs, although further studies are required to confirm their role as H3R antagonists.

Organotin (IV) compounds are known to induce apoptosis via the intrinsic mitochondrial pathway, which is a key mechanism of effective anticancer therapy. Their ability to selectively promote apoptotic cell death highlights their potential as chemotherapeutic agents. In this study, the in vitro effects of two triorganotin compounds, tributyltin propionate and tributyltin salicylate, on the human breast cancer cell line MDA-MB-231 were evaluated. In addition to their proven antitumor activity, these compounds may act as synthetic ligands for nuclear retinoid X receptors. Protein expression profiles were examined using gel electrophoresis and MALDI-TOF mass spectrometry, with a particular focus on heat shock proteins (HSPs), which are commonly overexpressed in cancer cells and contribute to tumor progression and therapeutic resistance. Both triorganotin derivatives significantly reduced HSP expression, suggesting that HSPs could be a promising target in cancer therapy.

The prognostic value of CT-detected tumor necrosis in advanced non-small cell lung cancer (NSCLC) treated with immune checkpoint inhibitor (ICI) monotherapy remains unclear. This two-center retrospective study investigated whether tumor necrosis on pretreatment CT independently predicts overall survival (OS).

Poly (ADP-ribose) polymerase (PARP) inhibitors demonstrate efficacy in breast cancer patients harboring pathogenic BRCA1/2 mutations. However, certain BRCA1 single nucleotide polymorphisms may alter protein function without complete loss of activity. This study investigates whether specific heterozygous BRCA1 single nucleotide polymorphisms within the central functional region of BRCA1 affect cellular sensitivity to PARP inhibition and explores the underlying transcriptomic mechanisms.

There is limited data on immune checkpoint inhibitor (ICI) use in patients with non-small cell lung cancer (NSCLC) and known pericardial effusions.

As cancer incidence rises in Asian countries, chemotherapy remains central to treatment amid rapid population aging and declining fertility in most of them. These trends underscore concern over long-term reproductive health, as chemotherapy-induced ovarian toxicity and premature ovarian insufficiency (POI) emerge as major late effects with unclear population-specific susceptibility. This review examines chemotherapy-induced ovarian damage via the PI3K-AKT-FOXO3 signaling axis, a key regulator of follicular quiescence, stress responses, and ovarian longevity. Evidence was synthesized from human studies, experimental models, and mechanistic investigations to develop this population-specific conceptual framework. Chemotherapy initiates DNA damage and oxidative stress, which subsequently activate interconnected pathways involving mitochondrial dysfunction, dysregulated autophagy, apoptosis, ferroptosis, inflammatory signaling, and dysregulation of the PI3K-AKT-FOXO3 axis, ultimately accelerating follicular activation and depletion. A distinctive contribution of this review is the integration of longevity-associated genetic susceptibility with ovarian vulnerability, highlighting evidence suggesting that certain FOXO3 and PI3K-AKT pathway variants, reported to be more prevalent in several Asian populations, may influence susceptibility to chemotherapy-induced ovarian injury. This review proposes a two-hit hypothesis as a conceptual framework integrating currently available molecular, experimental, and population-based evidence while acknowledging that direct clinical validation remains limited. Within this framework, longevity-associated genetic predisposition affecting the PI3K-AKT-FOXO3 axis constitutes the first hit, whereas chemotherapy-induced cellular stress represents the second hit, together accelerating follicular burnout and increasing the risk of POI. This framework supports future evaluation of genotype-informed risk stratification, individualized fertility preservation strategies, and prospective validation in Asian cancer cohorts, with the ultimate goal of informing ethnicity-specific fertility preservation strategies and optimized chemotherapy protocols.

Platinum anticancer drugs tend to target DNA whereas certain ruthenium and osmium organometallic compounds, including those with known anticancer activity, preferentially bind histone proteins in chromatin. We earlier found that Ru/Os arene 2-pyridinecarbothioamide antitumor agents display unique or partially overlapping profiles of histone protein binding in the nucleosome compared to Ru arene phosphaadamantane antimetastasis drugs, but the basis for this difference is unclear. Here, we structurally characterized the nucleosome binding effects of arene ligand substitutions and carried out a multiscale simulation analysis, which reveals that the interplay between metal cation and non-leaving ligand identity dictates adduct stability and whether complexes target electronegative surface patches, internal crevices, or both. We show that the nucleosome superhelical crevice acts as a small molecule selectivity filter and that multi-site binding profiles can be expanded or reduced through defined ligand substitutions, which modulate dynamic and steric attributes. Our findings suggest new avenues for rationally developing Ru/Os organometallics that could help expand the scope of chromatin-targeting therapeutics.

Immune checkpoint inhibitor (ICI) therapy for colorectal cancer (CRC) can be accompanied by endocrine adverse events, yet the comparative risk across commonly used regimens remains unclear. We therefore conducted a network meta-analysis of randomized controlled trials in CRC published up to November 22, 2025, estimating risk ratios (RRs) with 95% confidence intervals (CIs) and assessing risk of bias. Six RCTs were included. Relative to conventional therapy, ICI-based regimens were associated with a higher thyroid-related toxicity burden. Pembrolizumab and ICI+tyrosine kinase inhibitor (TKI) significantly increased the risk of hypothyroidism, whereas hyperthyroidism was significantly higher with ICI+TKI and ICI plus chemotherapy plus an anti-angiogenic antibody (ICI+Chem+Antiangio-Ab). Grade 1-2 adverse events were consistently increased across ICI-based treatments. For thyroiditis, diabetes mellitus, adrenal insufficiency, and grade 3-4 adverse events, effect estimates were imprecise with wide 95% CIs; nevertheless, SUCRA rankings tended to place ICI+TKI toward the higher-risk end for thyroiditis and diabetes. These findings indicate that ICI-containing strategies in CRC increase risks of endocrine adverse events-particularly for thyroid dysfunction-supporting the need for proactive endocrine monitoring and standardized management, while highlighting the limited precision of current evidence for rarer endpoints and severe toxicity.

Pancreatic ductal adenocarcinoma (PDAC) has an extremely poor prognosis. Immune checkpoint inhibitor (ICI) monotherapy has shown limited efficacy in PDAC, whereas the potential clinical value of first-line ICI-based combination regimens remains unclear. Through a systematic review and meta-analysis, this study aimed to evaluate the efficacy and safety of first-line ICI-based combination regimens in advanced PDAC.