Immune checkpoint inhibitors (ICIs) combined with platinum-based compounds are commonly used in the treatment of certain malignant tumors. This study aims to analyze adverse events (AEs) associated with the combination therapy of ICIs and platinum-based compounds by using the FAERS database.

Myocarditis attributable to immune checkpoint inhibitors is regarded as among the most serious complications of immunotherapeutic treatment. We report a case of gastric cancer who developed myocarditis, and subsequent late complications following treatment with nivolumab and ipilimumab. The patient was managed with corticosteroids, mycophenolate mofetil (MMF), and intravenous immunoglobulin G (IVIG), but later developed supraventricular tachycardia and deep vein thrombosis. This report emphasizes the need to enhance recognition of immune-related toxicities within non-oncology specialties to support prompt interdisciplinary collaboration and appropriate patient management. Additionally, patients can develop myocarditis-related complications even when clinically stable or near the end of treatment, underscoring the need for close and ongoing monitoring.

The purpose of this review is to highlight recently published research that can provide insight into how either sex or chemotherapeutics can impact cancer regulation of muscle anabolic resistance. Critical knowledge gaps are emphasized that are linked to cancer and treatment disruptions to muscle anabolic signaling. We speculate and propose a rationale for estrogen's protective effect against cancer-induced muscle anabolic resistance in females. Furthermore, there is growing evidence that many cancer treatments have the potential to exacerbate muscle anabolic resistance in both males and females. We present current evidence and speculate on how nutritional interventions could serve as key modulators of cancer-induced anabolic resistance in these conditions.

The addition of immune checkpoint inhibitor (ICI) to platinum-based chemotherapy has improved outcomes in patients with advanced non-small cell lung cancer (NSCLC). However, evidence on the efficacy of adding ICI to platinum retreatment in patients who relapse after perioperative platinum-based chemotherapy remains limited.

Phenotypic two-dimensional (2D) high-throughput screening (HTS) is a well-established approach extensively employed in oncological drug discovery by both Academia and the pharmaceutical industry. This methodology has played a pivotal role in the development of a wide range of systemic and targeted therapeutic anticancer agents for clinical use. Recent advances in automation, imaging technologies, and labware design have paved the way for image-based HTS in three-dimensional (3D) cell culture systems. These 3D systems enable the analysis of more physiologically relevant models that closely replicate the characteristics of tumors and their microenvironment. In this study, we present an image-based phenotypic 3D HTS assay utilizing imaging-compatible labware specifically designed to support spheroid formation.

We previously described the discovery of carbamate-derived small molecules as potent and selective lysophosphatidic acid receptor 1 (LPA1) antagonists. To further expand the library of LPA1 antagonists and potentially enhance their stability and potency, a urea moiety was introduced in replacement of the carbamate group and a series of LPA1 antagonists based on a urea scaffold were synthesized and evaluated. Within this series, several compounds exhibited potent LPA1 antagonism. Notably, compound 5f emerged as one of the most potent, with an IC50 of 215.2 nM in the cAMP assay and 7.9 nM in the calcium mobilization assay. Compound 5f demonstrated the ability to block LPA-induced cell migration and invasion in the triple-negative breast cancer cell line MDA-MB-231. These findings support further in vivo evaluation of compound 5f as a potential therapeutic agent targeting LPA1. The development of these urea-derived LPA1 antagonists in this study has expanded the repertoire of LPA1 antagonists and holds potential for the development of a novel therapy for metastatic triple-negative breast cancer.

Here, we present a protocol to address the limited intratumoral penetration of small-molecule drugs caused by the dense extracellular matrix (ECM) of pancreatic ductal adenocarcinoma (PDAC). Prodrugs offer great potential to overcome this challenge by enhancing drug penetration and tumor-killing efficacy. Squalene (SQ), a natural precursor for cholesterol biosynthesis with excellent biosafety and biocompatibility, can improve the membrane compatibility of hydrophilic drugs and enhance their cellular uptake when conjugated to chemotherapeutic agents or bioactive small molecules. In this study, we developed a novel lipophilic SQ-based prodrug system: the hydrophilic anticancer drug chidamide (CHI) was conjugated to SQ via an amide bond -- a linkage responsive to pancreatin and cathepsin B (key enzymes overexpressed in the PDAC microenvironment). This conjugation yielded an amphiphilic SQ-CHI prodrug, which was further self-assembled into folate (FA)-modified nanoparticles (FA-SQ-CHI NPs). The optimized NPs exhibited a uniform hydrodynamic diameter of 173.3 ± 1.5 nm, a polydispersity index (PDI) of 0.181 ± 0.18, a high drug loading capacity of 59.0% ± 0.77%, and a stable Zeta potential of -13.10 ± 0.86 mV. In vitro release studies showed that the NPs achieved 80.2% ± 4.22% cumulative drug release within 72 h in the presence of 0.25% pancreatin, while only 33%-38% release was observed in pH-adjusted buffers (pH 4.5 or 7.4) without enzymes. Cellular uptake assays confirmed that FA modification significantly enhanced intracellular delivery efficiency, with 1.8-2.3-fold higher fluorescence intensity in PDAC cells (PSN-1 and CFPAC-1) compared to non-targeted NPs at 12-24 h. The current protocol provides a comprehensive methodology for the synthesis and characterization of the prodrug, in vitro evaluation of enzyme-responsive release kinetics, and comparative analyses of therapeutic efficacy and tissue penetration, highlighting the nanocarrier's core advantages of targeted delivery, high drug loading, and enzyme-triggered controlled release.

Pancreatic neuroendocrine neoplasms (PanNENs) represent a rare and heterogeneous group of tumors with diverse biological behaviors and clinical outcomes, posing significant therapeutic challenges. Recent studies have suggested that certain proton pump inhibitors, including Lansoprazole, may possess direct anti-tumor properties beyond their classical role in acid suppression; however, their specific effects and molecular mechanisms in PanNENs remain largely unexplored. This study aims to investigate the anti-proliferative effects and elucidate the underlying molecular mechanisms of Lansoprazole in PanNEN models. Our findings demonstrate that Lansoprazole significantly upregulates the expression of DNA Damage Inducible Transcript 3 (DDIT3), a key stress-induced transcription factor. This upregulation leads to the subsequent inhibition of the oncogenic PI3K/AKT/mTOR signaling pathway, a central driver of cell growth and proliferation, resulting in marked suppression of PanNEN cell proliferation in vitro. Furthermore, we explored combination therapy strategies and found that Lansoprazole synergizes with everolimus, an established mTOR inhibitor used in PanNEN treatment. This combination enhances overall anti-tumor efficacy, suggesting a promising synergistic therapeutic strategy for PanNENs. These results not only reveal a novel, drug-repurposing approach for targeting PanNENs but also provide a mechanistic rationale for combining Lansoprazole with standard targeted therapies to improve patient outcomes.

Lung cancer has high mortality rates among both men and women worldwide. Nevertheless, mortality rates have been reported to decline with the advancement of novel therapeutic agents and the identification of new molecular targets. Schiff bases and triazine compounds have significant biological activity. For this purpose, new Schiff base derivative triazine compounds (TrzSchf 1-3) were synthesized in our study. The activities of the new compounds, characterized by spectroscopic techniques, against A549 lung cancer and MRC5 normal lung cells were identified in a series of studies. It was observed that TrzSchf 1-3 generally showed a growth-inhibitory effect against lung cancer cells (A549) and a non-toxic effect against normal lung cells (MRC5). Notably, TrzSchf 1 and TrzSchf 2, 3 exhibited prominent cytotoxic effects in A549 cells, with IC50 values of 14.24 and > 50 μM, respectively. It was observed that the compound with the most potent cytotoxicity against lung cancer cells was TrzSchf 1 (Selective Index: 3.62). In A549 cells, an increase in MAPK gene expression was observed for all compounds. It was observed that the expression of Caspase-3, CD40, CHK1, P27, P38, and P53 proapoptotic proteins increased by all compounds (TrzSchf 1-3), whereas the expression of antiapoptotic proteins such as BCL-2 and NFκB decreased by these compounds. The compounds are thought to be potential inhibitors of BCL-2 and NFκB, which are associated with cell death. Complementary and guiding in silico studies supported the experimental findings. BCL-2 was determined as the most favorable molecular target based on docking scores, and e-pharmacophore modeling further revealed key interaction features and enabled SAR analysis. The drug-likeness potential of the TrzSchf derivatives was evaluated based on Lipinski's Rule of Five parameters. Overall, both experimental and computational results suggest that TrzSchf 1-3 are promising lead candidates for further investigation in lung cancer therapy.

DHP107 is an oral paclitaxel enabling administration of paclitaxel without Cremophor EL, a vehicle used to improve the solubility of intravenous (IV) paclitaxel. The randomized phase II OPERA study investigated the efficacy and safety of DHP107 versus IV paclitaxel in patients with HER2-negative breast cancer.

Quantitative Structure-Activity Relationships are established in this work to predict the anticarcinogenic activities of flavonoids and related compounds in the MCF-7 breast cancer cell line. The selected descriptors tend to faithfully predict the [Formula: see text] and [Formula: see text] bioactivities, showing a straight-line trend in the correlation with the experimental data, even in this structurally diverse set of molecules. Finally, several structurally related compounds with unknown experimental anticarcinogenic activities are predicted. Therefore, the present study provides a guide for the rational design of potential new therapeutic molecules through the structure-activity parallelisms found. This work also demonstrates that QSAR models lead to evaluating whether the acquisition of experimental data is in agreement with the experimental protocol and methodologies, discriminating based on the domain of applicability and the fit to the QSAR model used.

Photothermal therapy (PTT) combined with chemotherapy is a promising cancer treatment approach, but its effectiveness is limited due to concerns about heat resistance mediated by heat shock proteins (HSPs) and the side effects of chemotherapy. In this study, we developed indocyanine green (ICG)-encapsulated tea leaf nanoparticles (TLNPs-ICG) as a photothermal nanoplatform. The TLNPs, approximately 140 nm in diameter, efficiently encapsulated ICG and demonstrated stable, concentration-dependent photothermal heating under 800 nm near-infrared irradiation. TLNPs-ICG were readily internalized by keratinocytes and melanoma cells, likely via the EGCG/67 kDa laminin receptor, and exhibited selective cytotoxicity against melanoma cells. When combined with near-infrared irradiation, TLNPs-ICG exhibited potent photothermal cell killing, whereas TLNPs or free ICG alone was only marginally effective. Importantly, TLNPs-ICG attenuated the upregulation of HSP70 and HSP90 and suppressed the acquisition of thermotolerance in vitro and in vivo. In a B16 melanoma mouse model, the intratumoral administration of TLNPs-ICG, combined with intermittent near-infrared irradiation, significantly suppressed tumor growth without apparent systemic toxicity. These results suggest that TLNPs-ICG are plant-derived biomaterials that integrate EGCG-mediated biochemical activity, heat shock regulation, and ICG-mediated photothermal effects, providing a platform for next-generation PTT-combined cancer therapy.

Acute promyelocytic leukemia (APL) is a highly curable subtype of AML, largely due to the introduction of differentiating therapy with all-trans retinoic acid and arsenic trioxide. While intravenous arsenic trioxide (ATO) is considered the standard-of-care in the United States, its prolonged administration and monitoring requirements pose logistical challenges that require high healthcare resource utilization and negatively impact quality of life.

Although FGFR2 is a well-validated oncogenic target, no selective FGFR2 inhibitors have been approved for clinical use. In this study, we report the discovery of 2H-pyrazolo[3,4-d]pyrimidin-4-amine derivative as novel, irreversible FGFR2 inhibitors. The optimal compound, PLW559, potently inhibited FGFR2 with an IC50 value of 13.59 nM and demonstrated exceptional selectivity over FGFR1, FGFR3, and FGFR4. Covalent binding to the target was confirmed by mass spectrometry. In cellular models, PLW559 exhibited potent and selective antiproliferative effects against FGFR2-driven cancer cells, effectively suppressed downstream FGFR2 signalling and induced cancer cell apoptosis. Notably, it showed minimal activity in non-FGFR2-dependent cells. This work presents a new class of selective FGFR2 inhibitors based on a novel scaffold, offering promising lead compounds for the development of FGFR2-target therapies.

Chemoimmunotherapy, particularly strategies that induce immunogenic cell death, has emerged as a promising approach to improved cancer treatment. Nonetheless, only a limited number of drugs can successfully stimulate an antitumor immune response in vivo. Recent studies have highlighted the potential of metal-based anticancer agents in chemoimmunotherapy. Herein, we report a novel piano-stool arene ruthenium(II) complex, Ru-4, which acts as a dual catalytic inhibitor of topoisomerase I and II. This inhibition induces DNA damage and activates the cGAS-STING signaling pathway, leading to the production of type I interferon and chemokines CCL5 and CXCL10. Ru-4 demonstrates potent cytotoxicity in vitro and elicits a robust antitumor immune response in vivo. Furthermore, Ru-4 exhibits a synergistic antitumor growth effect when combined with a PD-1 inhibitor. To the best of our knowledge, this study is the first to demonstrate how rationally designed ruthenium(II) complexes can promote a chemoimmunotherapeutic response via the activation of the cGAS-STING pathway through the dual catalytic inhibition of topoisomerases. It is thus expected to pave the way for the development of new chemoimmunotherapy strategies.

The optimal integration of radiotherapy (RT) and immune checkpoint inhibitors (ICI) for esophageal squamous cell carcinoma (ESCC) remains undefined. This study aimed to evaluate treatment patterns, hematologic dynamics, and prognostic factors in patients receiving combined RT and ICI.

Resistance to immune checkpoint inhibitors (ICIs) targeting the programmed cell death protein 1/programmed death ligand 1 (PD-1/PD-L1) axis remains a major obstacle in non-small cell lung cancer (NSCLC).

Hepatocellular carcinoma (HCC) is a malignant tumor with a high mortality rate globally, ranking among the top cancers in incidence and posing a serious human health threat. In recent years, with research advancement in traditional medicine, traditional Chinese medicine (TCM) has attracted increasing interest for its potential role in the management of hepatocellular carcinoma (HCC). As a comprehensive review, this article critically synthesizes the biological mechanisms and clinical application evidence of TCM extracts and classic formulas in HCC treatment, systematically detailing the important roles and specific mechanisms of TCM in inhibiting tumor growth, inducing apoptosis, enhancing immunity, and suppressing angiogenesis. This review aims to synthesize and analyze existing findings to provide a consolidated theoretical basis and identify potential research gaps. Furthermore, it seeks to explore new therapeutic concepts by bridging TCM theory with modern pharmacological approaches, thereby promoting the development of integrated strategies in oncology. Ultimately, we aim to contribute to the improvement of patient survival rates and quality of life. However, while preclinical evidence is promising, the clinical evidence base requires further strengthening through larger-scale, rigorously designed trials to validate efficacy and establish standardized protocols.

The emergence of drug-resistant cancers has led to the discovery of novel therapeutic agents. Medicinal plants are a promising source, with Dendrophthoe pentandra (L.) Miq. a parasitic plant used in ethnomedicine, showing promising anticancer potential. This study reviews preclinical evidence of the anticancer activity of D. pentandra, focusing on its phytochemical constituents and molecular mechanisms of action. A systematic search of Scopus and PubMed databases was conducted for preclinical studies published between 2015 and 2025. After screening, 13 articles met the eligibility criteria and were included in narrative synthesis. The 13 included studies demonstrated that D. pentandra extracts exhibit potent cytotoxic and antiproliferative effects against multiple cancer cell lines. The primary anticancer mechanism identified was the induction of apoptosis, which is frequently mediated by the upregulation of p53 and Bax proteins, downregulation of Bcl-2, and induction of cell cycle arrest at the G1/S or G2/M phase. Flavonoids, particularly quercetin, have been identified as the key bioactive phytoconstituents that contribute to these effects. In vivo studies further support these findings, showing that D. pentandra extract can inhibit tumor progression in colitis-associated cancer models by reducing inflammatory markers such as myeloperoxidase (MPO).

Breast cancer treatment continues to be limited by insufficient tumor selectivity and adverse systemic effects, highlighting the need for delivery systems that improve drug accumulation in malignant cells while minimizing exposure to healthy tissue. In this study, we designed an integrin-targeting nanosystem for drug repurposing by encapsulating mesalamine (MES) within a zeolitic imidazolate framework-8 nanocarrier (nZIF-8) and functionalizing the surface with an Arg-Gly-Asp (RGD) peptide via one-pot synthesis. The MES-RGD@nZIF-8 nanocarriers showed high encapsulation efficiency (99.69%) and preserved the structural and morphological characteristics of ZIF-8 following functionalization. Release studies demonstrated controlled MES diffusion at physiological pH and accelerated release under mildly acidic conditions, consistent with ZIF-8 degradation. Biological evaluation showed that MES-RGD@nZIF-8 induced 65% cytotoxicity at 48 h, outperforming free MES and non-targeted formulations. The elevated selectivity index (SI = 4.53) demonstrated preferential cytotoxicity toward breast cancer cells compared with normal cells, confirming the enhanced tumor selectivity of the formulation. Molecular docking simulations revealed that the presence of RGD in the nZIF-8 framework enhanced the binding affinity of MES by providing greater interaction sites compared to the pristine nZIF-8. These findings demonstrate that RGD-functionalized nZIF-8 is a promising platform for targeted drug repurposing in breast cancer therapy.