The discovery and therapeutic application of immune checkpoint inhibitors (ICIs) have significantly improved clinical outcomes in cancer treatment. However, the response rate is still low in gastrointestinal (GI) cancers. The gut microbiome's impact on immune modulation is a promising area for overcoming resistance to immunotherapy.

Seven novel 2-(2-phenylethyl)chromone-sesquiterpene hybrids (1-7) were successfully isolated from the ethanol extract of Hainan agarwood of Aquilaria sinensis under HPLC-MS guidance. Their structures were determined by extensive spectroscopic analysis, including 1D and 2D NMR, HRESIMS, IR, and experimental and computed ECD data. Their anti-inflammatory, cytotoxic, and anti-Helicobacter pylori activities were evaluated. Compounds 1-4 demonstrated significant suppression of nitric oxide production in LPS-stimulated RAW264.7 cells, with IC50 values ranged of 7.25-10.42 μM. Compounds 1-3, 5, 7 showed anti-H. pylori activity with MIC value of 20 μM, 4 and 6 exhibited MIC values of 40 μM. And every compound exhibited significant cytotoxicity in all five (K562, BEL-7402, SGC-7901, Hela and A549) human cancer cell lines examined, displaying overall IC50 value is between 16.77 ± 0.21 to 47.58 ± 0.27 μM, demonstrating broad-spectrum anticancer potential.

Cynaropicrin is a guaianolide-type sesquiterpene lactone primarily derived from plants within the Asteraceae family. Structurally, it features a distinctive 5-7-5 tricyclic framework, four exocyclic double bonds, and two hydroxyl groups. Due to its broad pharmacological activities, cynaropicrin garnered considerable scientific interest, with well-established protocols for its extraction and synthesis. Extensive studies have demonstrated that cynaropicrin exhibits remarkable antitumor activities by effectively inhibiting the proliferation of various malignancies, such as lung cancer, melanoma, and breast cancer. The underlying mechanisms are primarily associated with the regulation of cell cycle progression and apoptosis-related pathways. Moreover, cynaropicrin significantly enhances the efficacy of chemotherapeutic agents including temozolomide, cisplatin, and docetaxel, suggesting promising potential for combination therapy. Beyond its antitumor properties, cynaropicrin exhibits a broad spectrum of bioactivities, including antioxidant, antiviral, antiparasitic, and immunomodulatory effects, primarily via the modulation of signaling pathways like NF-κB. Structure-activity relationship (SAR) studies further indicate that the side chain, hydrophilicity of the OH-3 and OH-19 substituents, and the C17-C18 exo-olefin structure critically influence its NF-κB inhibitory activity. This review comprehensively synthesizes current knowledge regarding the mechanisms of action and SAR insight of cynaropicrin across various pathophysiological processes, evaluates its prospects for clinical application, and aims to provide a foundational framework to guide future research and development efforts involving this compound.

Doxorubicin (Dox) is a cornerstone chemotherapeutic agent whose clinical use is limited by nephrotoxicity driven by oxidative stress, renin-angiotensin system (RAS) imbalance, activation of the profibrotic Wnt/β-catenin pathway, and suppression of the renoprotective protein α-Klotho. Substance P (SP) signaling through the neurokinin-1 (NK-1) receptor is a mediator of inflammatory injury; however, its role in Dox-induced nephrotoxicity remains unexplored. Therefore, we investigated whether pharmacological blockade of the NK-1 receptor with MK-0869 could alleviate Dox-induced nephrotoxicity and modulate α-Klotho-associated antioxidant and signaling pathways. Male Sprague-Dawley rats were assigned to control, MK-0869, Dox, and Dox + MK-0869 groups. Dox nephrotoxicity was induced cumulatively (16 mg/kg over 28 days), while MK-0869 was administered orally (10 mg/kg/day). Renal function markers, signaling and oxidative stress markers were assessed using ELISA, qRT-PCR, Western blotting, immunohistochemistry, and histopathological analysis. MK-0869 markedly attenuated Dox-induced renal injury, significantly improving renal function and histological architecture. Specifically, compared with Dox-treated rats, MK-0869 reduced serum creatinine by 53% (p < 0.0001) while restoring renal α-Klotho levels nearly two-fold (p < 0.0001). Mechanistically, NK-1 receptor blockade suppressed SP signaling, restored Ang-(1-7) levels while attenuating the Ang II/AT-1 receptor axis, activated the Nrf2/HO-1 antioxidant pathway, reinstated FoxO3a-dependent SOD2 expression, and inhibited Wnt-1/β-catenin signaling, thereby reducing renal fibrosis. In conclusion, NK-1 receptor blockade confers robust protection against Dox-induced nephrotoxicity through integrated modulation of α-Klotho signaling, RAS balance, oxidative stress, and profibrotic pathways. These findings support MK-0869 as a promising renoprotective adjunct during Dox therapy and warrant further studies to evaluate long-term safety and translational potential.

Breast cancer is one of the most prevalent cancers worldwide, ranked as the second most diagnosed cancer and the fourth leading cause of cancer-related deaths. Despite the availability of FDA-approved therapies, limitations such as drug resistance and off-target effects highlight the need for novel, multitargeted therapeutic agents. In this study, we aimed to identify and design an in-silico promising multitarget drug for breast cancer by simultaneously targeting three critical proteins: Glucocorticoid Receptor, Estrogen Receptor-alpha (ER-alpha), and Cyclin-Dependent Kinase 2 (CDK2). FDA-approved drugs corresponding to these targets were initially subjected to multitarget molecular docking to evaluate their binding affinities. Based on this screening, the 15 highest-ranking ligands were selected and underwent molecular enumeration, resulting in the generation of 14,750 novel derivative compounds. The re-docking identified 1-((R)-2,3-dihydroxypropyl) -3-(3-((R)-1-5-methyl-1H-pyrrolo [2,3-b]pyridin-3-yl)ethyl)phenyl) urea (DdpMPyPEPhU) (Patent No. 202024101028.0) as a promising multitarget candidate. The compound exhibited enhanced binding pocket engagement through numerous stabilising interactions, including hydrogen bonds, π-π stacking, and π-cation interactions, with high docking scores (-14.869 to -4.57 kcal/mol) and favourable Molecular Mechanics Generalised Born Surface Area (MM-GBSA) energies (-72.32 to -11.97 kcal/mol). Comparative docking and pharmacokinetic analyses with standard drugs Lapatinib and Tamoxifen indicated better drug-like properties and pharmacokinetic advantages for DdpMPyPEPhU. Additional validation using Density Functional Theory (DFT) optimisation, 5 ns WaterMap analysis, and 250 ns molecular dynamics simulations under neutralised conditions confirmed structural stability and strong intermolecular interactions, supported by binding free energy calculations. Overall, our computational findings suggest that DdpMPyPEPhU is a promising therapeutic candidate for breast cancer, providing a rational basis for further experimental evaluation.

Palbociclib (PBB) is an oral cyclin-dependent kinase 4/6 (CDK4/6) inhibitor approved for the treatment of HR+/HER2- breast cancer. However, poor adherence and limited tolerability of oral administration often compromise its therapeutic effectiveness, especially in palliative care for metastatic conditions. Dose reductions are frequently required to manage toxicity, but lower doses can still provide effective tumour control with reduced neutropenia risk, thereby improving quality of life and progression-free survival. Developing a long-acting injectable (LAI) formulation of PBB offers significant advantages for sustained therapy in advanced-stage cancer management.

To assess thyroid immune-related adverse events (irAEs) in patients receiving immune checkpoint inhibitors (ICIs) and estimate future endocrine service burden.

Cholangiocarcinoma (CCA) continues to be classified as a rare cancer with high mortality rates, underscoring the urgent need for more effective systemic treatment strategies. The widespread implementation of next-generation sequencing has enabled comprehensive characterization of the genomic landscape of CCA, revealing a relatively high prevalence of actionable genetic alterations.

Immune checkpoint inhibitors (ICIs) have reshaped the treatment landscape of several cancer types. However, their effectiveness remains limited to a subset of patients, in part due to insufficient preexisting antitumor immunity. In this study, we hypothesized that intracellular delivery of noncoding dsDNA encapsulated in lipid nanoparticles (DNA-LNPs), which have recently been demonstrated to activate both STING and absent in melanoma 2 (AIM2) pathways, could enhance antitumor immune responses and potentiate ICI therapy. Using multiple animal models of cancer, including hepatocellular carcinoma, acute myeloid leukemia, melanoma, and melanoma lung metastasis, we show that DNA-LNP treatment triggered strong cytokine induction and robust CD8+ T cell recruitment to the tumor microenvironment. This immune activation mediated potent CD8+ T cell-dependent antitumor effects and prolonged animal survival across multiple models. Notably, empty LNPs did not elicit potent cytokine elevation or antitumor effects, suggesting that these responses are triggered by the activation of cytosolic DNA-sensing pathways. Moreover, DNA-LNPs synergized with anti-PD-L1, substantially extending animal survival in both ICI-responsive and ICI-resistant tumor models. These findings position DNA-LNPs as a promising immunotherapy strategy, either alone or in combination with ICI therapies, to enhance antitumor immunity across diverse cancer types.

Small cell lung cancer (SCLC) initially responds well to cisplatin-based chemotherapy, but rapid development of drug resistance limits long-term efficacy and subsequent treatment options. Understanding the multifactorial mechanisms of cisplatin resistance is essential for improving patient outcomes. This review synthesizes recent preclinical and clinical advances, focusing on seven key resistance mechanisms and emerging therapeutic strategies, including immunotherapy, targeted therapy, and novel chemotherapeutic agents.

In this study, we report the design and evaluation of Anlo@MOF-Lipo (AML), a liposome coated, small sized MIL-101(Fe) metal-organic framework (MOF) for targeted delivery of the multi target tyrosine kinase inhibitor anlotinib in lung cancer treatment.

To address the poor water solubility and low bioavailability of the curcumin derivative CU1, this study constructed a long-circulating pH-sensitive nanoliposome (CU1-LCpHL) as its delivery system.

Malignant tumors seriously affect people's normal lives, but the effective treatment of cancer needs to be further improved.

Immune checkpoint inhibitors (ICIs) combined with standard chemotherapy (CT) or chemoradiotherapy (CRT) have shown promising results in recent randomized controlled trials (RCTs) for advanced or recurrent cervical cancer (CC). However, comprehensive evidence is needed to evaluate their efficacy and safety, particularly in the context of patient subgroups and immune response mechanisms. This meta-analysis aimed to synthesize data from RCTs and apply trial sequential analysis (TSA) to validate findings.

Neuroblastoma constitutes a solid tumor in pediatric populations, characterized by a dismal prognosis and a scarcity of effective therapeutic interventions. Medicinal flora from South Africa represents valuable sources of bioactive phytometabolites with potential relevance to neuroblastoma. This study employed an integrated workflow merging untargeted UPLC-MS/MS metabolomics, mitochondrial functional assays, and in silico absorption, distribution, metabolism, and excretion (ADME) prediction to systematically identify bioactive metabolites from Acorus calamus and Lippia javanica with activity against SH-SY5Y neuroblastoma cells. Cytotoxic effects were quantified utilizing the CCK-8 assay, while mitochondrial membrane potential (ΔΨm) was conducted through JC-1 flow cytometry. Untargeted UPLC-MS/MS profiling yielded metabolomic fingerprints, through PCA, PLS-DA, and OPLS-DA. ADME and drug-likeness were predicted using SWISSADME. Both plant extracts exhibited dose-dependent inhibition of SH-SY5Y cell viability, with IC50 values determined at 0.2886 μg/μL for A. calamus and 0.3066 μg/μL for L. javanica. The ΔΨm assessment indicated enhanced mitochondrial polarization (68.2% and 65.4% compared to 58.8% in untreated controls), implying modulation of mitochondrial functional status. Metabolomic profiling unveiled distinct phytochemical signatures, including flavonoids, phenolics, jasmonates, and alkaloids, exhibiting significant species-level differentiation (F = 936.71, R2 = 0.989, p = 0.005). Notable metabolites such as isopropyl β-glucoside, 6β-hydroxymethandienone, and 7-epi-12-hydroxyjasmonic acid demonstrated favorable ADME characteristics and permeability across the blood-brain barrier. This investigation elucidates that A. calamus and L. javanica possess potential efficacy against neuroblastoma, underscoring the translational potential of African medicinal flora in pediatric oncology and necessitating further preclinical exploration.

Radioresistance compromises pancreatic cancer radiotherapy outcomes, making the identification of radiosensitizing strategies a critical priority. AZD5153, a novel specific Bromodomain-containing protein 4 (BRD4) inhibitor, has demonstrated efficacy in relapsed/refractory solid tumors and lymphomas. Our research focuses on investigating the effect of AZD5153 on the radiotherapy sensitivity of human pancreatic cancer cells, and its underlying mechanisms.

Cetuximab is an approved therapy for metastatic colorectal cancer (CRC) with wild-type RAS and BRAF; however, additional resistance mechanisms beyond genetic mutations remain poorly understood. Butyrate, a key metabolite produced by the gut microbiome and present in the circulatory system, has been reported to supply cellular energy and modulate the epidermal growth factor receptor (EGFR) downstream signaling pathway. However, whether butyrate affects the resistance to cetuximab is still unknown.

Vepdegestrant (ARV-471) is an orally bioavailable, proteolysis-targeting chimera (PROTAC)-based estrogen receptor (ER) degrader and is among the most clinically advanced ER-targeting PROTAC degraders, identified through a rational medicinal chemistry optimization campaign. It is being developed as an oral small-molecule endocrine therapy for advanced or metastatic ER-positive, human epidermal growth factor receptor 2 (HER2)-negative breast cancer, with particular relevance for tumors harboring ESR1 mutations. On June 6, 2025, Arvinas and Pfizer submitted a New Drug Application (NDA) for vepdegestrant to the U.S. Food and Drug Administration (FDA), representing an important step in the clinical translation of PROTAC technology. This review summarizes the design, synthesis, degradation mechanism, preclinical pharmacology, and clinical development of vepdegestrant and discusses the broader implications and future prospects of oral PROTAC-based ER degraders in breast cancer therapy.

Advances in cancer treatment have led to improved survival rates, but challenges related to health-related quality of life (HRQoL) persist, often exacerbated by sleep disturbances. We present a pre-registered, secondary analysis of HRQoL from a trial of sleep interventions among women with early or advanced breast cancer receiving chemotherapy.

This study aimed to comprehensively investigate the anti-ovarian cancer (OC) efficacy of Yiyi Fuzi Baijiang Powder (YFBP), identify its key chemical constituents, and elucidate the underlying mechanisms of action.