Clinical treatment of prostate cancer, particularly metastatic castration-resistant prostate cancer (mCRPC), mainly depends on targeting prostate-specific membrane antigen (PSMA), also known as glutamate carboxypeptidase II (GCPII). Toward this, small molecule-drug conjugates (SMDCs), consisting of a PSMA-targeting ligand along with a chemotherapeutic, have emerged as an important targeted therapeutic tool. Herein, we have designed 39 ligands with varied targeting heads and linkers and have analyzed their efficacy in silico using molecular docking and molecular dynamics simulation. The best-docked compound was further synthesized, conjugated with doxorubicin via an acid-labile imine linkage to yield a novel PSMA-Dox conjugate. This conjugate was evaluated in vitro in PSMA-positive (LNCaP and C4-2 cells) and PSMA-negative (PC3 cells) to establish its selectivity toward PSMA, as well as to ascertain its selective cytotoxicity toward PSMA-positive cells. Further, cell cycle analysis confirmed the efficacy of the conjugate to induce apoptosis in PSMA-positive cancer cells. Thus, this study demonstrates a new SMDC which can serve as a template for creating new analogs with enhanced targeting and anticancer efficacy.

Actinomycins constitute a class of bioactive compounds known for their potent cytotoxic properties. Among them, actinomycin D, isolated in the 1940s from Streptomyces antibioticus, is the most extensively studied derivative. Structurally, actinomycins are characterized by a planar phenoxazinone chromophore flanked by two cyclic pentapeptides. They exert their biological effects primarily through DNA intercalation and transcription inhibition. Despite its remarkable bioactivity, the clinical application of actinomycin D is limited by significant adverse effects, including hepatotoxicity and restricted selectivity. These limitations underscore the need for structurally optimized analogs with improved therapeutic profiles and reduced toxicity. Over the decades, natural product discovery, precursor-directed biosynthesis, and synthetic modification have yielded more than 70 structurally distinct derivatives, incorporating variations in both the peptide rings and the chromophore core. These structural modifications have resulted in diverse antibacterial, antiviral, and cytotoxic activities. Thus, this review critically examines the historical development, chemical diversity, and in vitro and preclinical bioactivity of actinomycin derivatives, highlighting key structural modifications over time and discussing their implications for future drug development.

Photodynamic therapy (PDT) is a clinically approved therapeutic modality with great potential for the treatment of cancers due to its excellent spatiotemporal selectivity and noninvasivenes. A combination of light-controlled chemotherapy (PACT) and PDT in one molecule has the potential to overcome crucial drawbacks of both Pt-based chemotherapy and PDT via a synergetic effect. Herein, we report a Pt(IV)-BODIPY agent for dual light-controlled chemophotodynamic therapy, a Pt(IV) prodrug with a BODIPY orthogonal dimer in the axial position. The orthogonal arrangement of the fluorophores results in a long-lived, "heavy-atom-free" triplet state of the dimeric fluorophore. The high quantum yield of singlet oxygen for the dimer fluorophore and the Pt(IV) prodrug based on it was confirmed, and the formation of the triplet state was demonstrated by flash photolysis. The excellent photosensitive properties of the Pt(IV) prodrug on SK-BR-3 and MCF-7 tumor cells demonstrate photocontrolled toxicity and potential for the development of dual therapy conjugates.

Cervical cancer is the fourth most common cancer and the fourth leading cause of cancer‑related mortality among women worldwide. Tangeretin (TAN), a polymethoxylated flavonoid derived from citrus fruit peel, exhibits relatively high structural stability due to its methoxy groups and exerts anticancer effects in various malignancies, including lung, liver and breast cancer. However, to the best of our knowledge, the anticancer effects of TAN in cervical cancer remain insufficiently explored. The present study investigated the mechanisms underlying the anticancer effects of TAN on the CaSki cervical cancer cell line. Cell viability was evaluated using the EZ‑Cytox cell viability assay. The colony formation and cell cycle arrest assays demonstrated that TAN inhibited cell proliferation by inducing G1 phase arrest. The wound‑healing and Transwell migration assays demonstrated that TAN could reduce the migratory ability of CaSki cells, and the Annexin V/propidium iodide staining assay revealed that TAN increased the apoptotic cell population. Mitochondrial reactive oxygen species (ROS) were identified using MitoSOX™ staining and the mitochondrial membrane potential (MMP) was detected using JC‑1 staining. The findings of these assays suggested that TAN could increase mitochondrial ROS levels and decrease mitochondrial MMP in CaSki cells. Western blot analysis showed that TAN upregulated the protein expression levels of E‑cadherin and Bax. In addition, TAN restored the tumor suppressor protein p53. Collectively, these findings suggested that may exhibit anticancer activity in CaSki cells.

Advanced gastric and gastroesophageal junction (G/GEJ) adenocarcinomas are characterized by an aggressive course and a very poor prognosis. Due to the limited benefit of immunotherapy in patients with HER2-negative tumors, new therapeutic targets are sought. Zolbetuximab is a chimeric monoclonal antibody targeting the CLDN18.2 protein, which is overexpressed in 50-80% of gastric cancers.

Rituximab and obinutuzumab share the CD20 target but are used across distinct B-cell non-Hodgkin lymphoma (B-NHL) subtypes, treatment backbones, and clinical eras. Their real-world adverse event (AE) reporting patterns remain incompletely characterized.

Adipose-derived stem cells (ADSCs) are widely used in regenerative medicine, but their functionality declines under chemotherapeutic stress. Doxorubicin (Dox) is an effective anticancer agent known to induce long-term toxicity in healthy tissues. Increasing evidence suggests that Dox promotes cellular dysfunction, including apoptosis, promotion of oxidative stress, and premature senescence. The SAPK/JNK signaling pathway is implicated in stress responses and may contribute to Dox-induced aging in stem cells. However, its role in ADSC senescence and functional decline remains unclear. This study evaluated the effects of Dox on ADSC viability and aging-associated processes, with a focus on SAPK/JNK signaling. ADSCs exposed to 0.1-100 μM Dox for 24 h showed reduced mitochondrial activity and ATP levels at clinically relevant doses (5 μM), along with disrupted cell cycle progression and cytoskeletal alterations. Dox induced both apoptosis and premature senescence and increased oxidative stress. These effects were accompanied by alterations in SAPK/JNK pathway expression. Overall, Dox promoted ADSC dysfunction, highlighting potential limitations in the therapeutic use of ADSCs during chemotherapy and emphasizing the need for protective strategies. Alterations in the SAPK/JNK signaling pathway were observed in response to Dox-induced stress, suggesting that this pathway may contribute to the cellular stress response. These findings suggest that the development of approaches to preserve ADSC function and mitigate Dox toxicity is critical for improving the safety and efficacy of regenerative medicine applications.

Pancreatic cancer remains one of the most aggressive malignancies with limited therapeutic options and poor prognosis. Erlotinib (OSI-774), a small-molecule tyrosine kinase inhibitor (TKI), is clinically used in combination with gemcitabine, yet its efficacy is limited by modest improvements in overall survival (OS) and significant side effects. The aggregation of erlotinib in aqueous solutions further restricts its bioavailability. This study investigates the potential of Congo red (CR), a supramolecular carrier, to enhance the therapeutic impact of erlotinib against pancreatic cancer cells. Biophysical analyses using UV-visible spectroscopy (UV-Vis) and dynamic light scattering (DLS) confirmed the formation of stable CR-erlotinib co-aggregates with optimal molar ratio of 5:1. The effects of erlotinib alone and in combination with CR (CR:OSI-774) were evaluated on two pancreatic cancer cell lines (PANC-1 and BxPC-3). CR:OSI-774 complexes demonstrated significantly lower IC50 and IC90 values compared to erlotinib monotherapy, indicating enhanced anti-proliferative effects. While erlotinib induced apoptosis, CR:OSI-774 primarily triggered necrotic cell death. Importantly, both compounds significantly inhibited cancer cell migration and invasion, with CR:OSI-774 showing superior inhibition of invasive capacity. CR alone did not negatively affect cell viability or apoptosis/necrosis rates. Nanomechanical measurements using atomic force microscopy revealed an increase in cellular stiffness after treatment, particularly in cells exposed to the CR-erlotinib complex, suggesting changes in cytoskeletal organization associated with reduced motility. Furthermore, quantitative protein analysis using the Jess capillary electrophoresis system revealed a decrease in AKT phosphorylation without significant changes in total AKT levels, indicating effective modulation of EGFR signaling via supramolecular aggregation. These findings suggest that supramolecular aggregation with CR represents a promising strategy to enhance erlotinib efficacy in pancreatic cancer therapy while potentially reducing systemic toxicity. The approach opens new avenues for personalized medicine and targeted anti-cancer therapy.

Doxorubicin (DOX) is a commonly prescribed chemotherapeutic agent whose clinical application is limited by its toxicity to rapidly dividing organs, particularly the testes.This study explored the protective potential of ferulic acid-loaded niosomes (FA-NIO) against DOX-induced testicular dysfunction in rats and elucidated the underlying molecular mechanisms. Forty male rats were allocated into four groups: Group 1 was given saline, Group 2 was given DOX, Group 3 was given DOX + free FA, and Group 4 was given DOX + FA-NIO. Serum reproductive hormone levels, testicular oxidative stress indices, and the expression of genes and proteins relevant to NLRP3 inflammasome signaling, apoptosis (Bax and Bcl-2), and steroidogenesis (StAR, CYP11A1, and 3β-HSD) were assessed, along with histopathological changes in the testicular tissue. DOX administration significantly increased MDA (malondialdehyde) while suppressing antioxidant defences, accompanied by hormonal imbalance, severe histopathological damage, upregulation of Bax, NLRP3, and IL-1β, downregulation of Bcl-2, and inhibition of steroidogenic gene expression. On the other hand, these changes were partially mitigated in the DOX + free FA group. Notably, FA-NIO treatment reduced histopathological damage, normalised reproductive hormone levels, markedly increased steroidogenesis-related gene expression, suppressed apoptotic and inflammasome-related gene expression, and greatly restored antioxidant capacity. Compared with DOX + free FA, FA-NIO consistently demonstrated greater protective efficacy. In summary, FA-NIO targets oxidative stress-mediated apoptosis, attenuates NLRP3 inflammasome-related signaling, and restores steroidogenic function, thereby successfully attenuating DOX-induced testicular toxicity. These results suggest that FA-NIO may represent a promising nanotherapeutic strategy for attenuating chemotherapy-induced reproductive toxicity in a rat model.

The innovation of a therapeutic agent with dual anti-inflammatory, anticancer and reversing the dynamic of microtubules like colchicine was crucial. VEGFR2 inhibition has been established as a therapeutic approach for managing cancer, the colchicine site, situated on ß-tubulin and α-tubulin was also considered in cancer development, and metastasis. Moreover, uncontrolled inflammation predisposes to pleiotropic effects leading to cancer development and promoting all stages of tumorigenesis. A polymeric state of a novel one-dimensional palladium-based metal-organic framework (1D Pd-MOF), resulting from the coordination of pyrazine with palladium nuclei to achieve the more pronounced effect of polynuclear characteristics of palladium compared to mononuclear compounds, was designed, synthesized, and screened for its anticancer activity against the A549 lung cancer cell line, with comparison to normal cells. The characterization was performed using different techniques and supported by DFT investigations. The 1D Pd MOF exhibited a potent cytotoxic effect, with an IC50 value of 78.21 ± 0.41 µg/mL against the A549 lung cancer cell line, while showing minimal toxicity toward the normal WI-38 cell line. To investigate the inhibitory activity of the 1D Pd-MOF towards VEGFR2 kinase and to confirm itseffective molecular target, VEGFR2 kinase inhibition was evaluated. The results demonstrated promising VEGFR2 inhibitory activity with a moderate IC50 value of 0.658 ± 0.023 µg/mL, compared with an IC50 value of 0.079 ± 0.003 µg/mL for sorafenib, the reference drug. This activity was further supported by significant inhibition of VEGFR2 gene expression and protein levels compared with untreated control cells. Our results revealed that 1D Pd-MOF is a promising tubulin-interacting compound, as it binds to the colchicine-binding site on tubulin and competes with colchicine in vitro, with an IC50 value of 3.350 ± 0.21 µg/mL. These findings confirm tubulin as a molecular target of the 1D Pd-MOF and support its observed cytotoxic activity. Furthermore, the 1D Pd-MOF significantly upregulated the expression levels of BAX, P53, and caspase-3 genes, while downregulating CDK4, cyclin D1, and BCL2 genes relative to the control group, suggesting growth inhibition and induction of apoptosis in treated lung carcinoma cells. These findings confirm that the 1D Pd-MOF exerts a clear anticancer effect by triggering programmed cell death through apoptosis. In addition, treatment with the 1D Pd-MOF resulted in substantial accumulation of cells in the sub-G1 fraction, accompanied by a corresponding reduction in the G2/M phase, indicating that its cytotoxic efficacy is primarily mediated through apoptosis induction rather than cell cycle arrest at a specific checkpoint. The anti-inflammatory activity of the 1D Pd-MOF was established by its inhibition of nitric oxide (NO) production in LPS-stimulated RAW cells. Molecular docking studies showed good agreement with the experimental biological findings.

Nanotechnology provides innovative solutions to biomedical and agricultural challenges, and silver nanoparticles (AgNPs) are of particular interest due to their broad-spectrum bioactivity. This study aimed to green-synthesize AgNPs using Buddleja asiatica leaf extract, characterize the nanoparticles, and evaluate antibacterial, antioxidant, anticancer, and phytotoxic/phytostimulatory activities. AgNP formation was confirmed by UV-visible spectroscopy (SPR peak at 420 nm). XRD verified a crystalline face-centered cubic structure, while SEM showed predominantly near-spherical nanoparticles (10-22 nm). FTIR indicated plant-derived functional groups involved in stabilization. Biologically, BA-AgNPs exhibited strong antibacterial activity against a Gram-positive clinical isolate (Streptococcus sp.) and Gram-negative bacteria, with the largest inhibition zone of 14 ± 0.57 mm at 0.9 mg/mL. Antioxidant activity reached 88.12% DPPH scavenging at 100 ppm, compared with 80.90% for ascorbic acid under the same assay conditions. BA-AgNPs showed concentration-dependent cytotoxicity in RD cells, with cell death ranging from 87.00% at 100 mg/mL to 5.33% at 0.39062 mg/mL; however, IC50 is reported only as an estimated range of 6.25-12.5 mg/mL based on the concentration interval where cytotoxicity crossed 50%. In wheat, lower concentrations showed phytostimulatory trends, with the strongest response at 50 mg/L, while 1000 mg/L caused inhibitory effects. This is the first comprehensive report on B. asiatica-mediated AgNP synthesis and multifunctional bioactivity, highlighting BA-AgNPs as a sustainable nanomaterial for antimicrobial, antioxidant, anticancer, and agricultural applications, while emphasizing the need for future stability, mechanistic, and translational safety studies.

Gastric cancer (GC) remains a leading cause of cancer-related mortality worldwide, driven by late-stage diagnosis, metastatic progression, and therapeutic resistance. Src homology region 2 domain-containing phosphatase 2 (SHP2) has emerged as a critical regulator of oncogenic signaling in gastric tumorigenesis, yet its therapeutic targeting remains underexplored. In this study, we evaluated the anti-cancer efficacy of NSC 57774, a novel SHP2 inhibitor, using integrated bioinformatics and functional assays in AGS gastric cancer cells. Analysis of The Cancer Genome Atlas (TCGA) and UALCAN datasets revealed marked upregulation of SHP2 and multiple receptor tyrosine kinases in gastric cancer tissues. NSC 57774 potently inhibited cell proliferation and migration, demonstrating selective cytotoxicity towards cancer cells over non-cancerous fibroblasts. Mechanistically, NSC 57774 disrupted key oncogenic pathways including MAPK/ERK, AKT and STAT3 in a concentration- and time-dependent manner, with higher doses achieving more sustained pathway suppression. NSC 57774 suppressed NF-κB inflammatory signaling at early timepoints and induced cleaved caspase-3 across all treatment groups at 72 hours, indicative of pro-apoptotic activity. A paradoxical late-phase increase in phospho-p38 was observed at 72 hours, consistent with a compensatory pro-apoptotic stress response. Comparative analysis revealed that NSC 57774 outperformed the commercial SHP2 inhibitor NSC 87877 and doxorubicin in reducing viability and migration of gastric cancer cells. Collectively, these findings position NSC 57774 as a promising candidate for targeted gastric cancer therapy, capable of disrupting multiple signaling pathways involved in tumor progression, metastasis, and inflammation, warranting further preclinical and clinical investigation.

Mirvetuximab soravtansine is an antibody-drug conjugate targeting folate receptor alpha (FRα), which is used in the treatment of platinum-resistant ovarian cancer. Its administration is associated with a distinct spectrum of ocular adverse events, representing a clinically relevant limitation of therapy. The most common manifestations include keratopathy, blurred vision, and dry eye symptoms. These effects are generally reversible and manageable upon appropriate ophthalmologic monitoring. This review summarizes the current knowledge regarding the mechanisms, clinical presentation, incidence, prevention, and management of mirvetuximab-associated ocular toxicity.

Poly(ADP-ribose) polymerase inhibitors (PARPi) have shown limited efficacy in gastric cancer, primarily due to the rarity of inherent homologous recombination (HR) deficiency. The nuclear Arp2/3 complex was recently implicated in DNA double-strand break repair via HR. Here, we investigate whether pharmacological inhibition of Arp2/3 can induce a functional HR-deficient state to synergize with PARPi in gastric cancer cells.

Glioblastoma (GBM) frequently develops resistance to temozolomide (TMZ), limiting the effectiveness of standard therapy. Histone deacetylase (HDAC) inhibitors have emerged as potential chemosensitizers; however, the comparative performance of these inhibitors and the associated mechanistic impact remain incompletely characterized.

Cancer neuroscience has emerged as a field that explores the bidirectional interactions between tumors and the nervous system. From this perspective, we review the pharmacological and neurobiological effects of kinase inhibitors, which are widely used as anticancer therapeutics. Certain kinase inhibitors not only exert potent antitumor activity but also modulate neural function as a consequence of kinase inhibition. Representative examples include small molecules and therapeutic antibodies targeting the tropomyosin receptor kinase (Trk), rearranged during transfection (RET), vascular endothelial growth factor/ vascular endothelial growth factor receptor (VEGF/VEGFR), epidermal growth factor receptor (EGFR), and anaplastic lymphoma kinase (ALK) signaling pathways. These agents influence the nervous system through molecular mechanisms, examples of which include TrkA-mediated pain perception and growth differentiation factor 15/RET signaling-dependent appetite regulation. Elucidating these mechanistic intersections between oncogenic and neural signaling can broaden our understanding of tumor-nerve crosstalk.

A common cause of multidrug-resistant (MDR) cancer is imbalanced redox signaling, which reduces the effectiveness of chemotherapy and promotes regrowth of cancer cells. Amplification of thioredoxin reductase (TrxR) and activation of the Keap1-Nrf2-FOXO3 pathway may contribute to enhanced drug efflux, strengthens antioxidant defenses, and resistance to oxidative stress-induced apoptosis in certain tumors. Redox-based drug repurposing offers a promising strategy to overcome MDR by targeting these shortcomings. Repurposing drugs including metformin, auranofin, brusatol, and natural polyphenols increase reactive oxygen species (ROS) and make MDR cells more sensitive to chemotherapy via modulation and inhibiting Nrf2 or TrxR. Nanotechnology advancements and combination of repurposed drugs with anticancer drugs, ferroptosis inducers may improve tumor selectivity while lowering systemic toxicity. Preclinical experiments show effectiveness by suppressing antioxidant pathways, inhibiting efflux pump function, and delivering drugs in a redox-responsive manner. Next-generation tumor-selective delivery systems, adaptive clinical trial designs, and biomarker-driven patient classification based on TrxR expression or Keap1/Nrf2 mutations are the main areas of focus. Translation into clinical practice could be accelerated by combining specific redox profiling, nanocarrier technologies, and pharmacokinetics. For MDR cancer, redox-targeted drug repurposing is an effective, precision-based strategy for recovering chemosensitivity and enhancing treatment outcomes.

To assess the protective effects of live combined bifidobacterium, lactobacillus, enterococcus, and glutamine on diarrhea associated with chemotherapy and inflammatory markers in colorectal cancer patients (CCP). A retrospective analysis was conducted on the clinical data of patients with colorectal cancer who received chemotherapy at the People's Hospital of Pailin County, Chongqing from December 2022 to December 2024. There were 59 cases in the control group and 59 cases in the study group. The control group received treatment with triple live bifidobacterium, while the study group received combined treatment with glutamine in addition to the treatment of the control group. We compared levels of inflammatory markers, intestinal barrier functions, immune responses, and diarrhea incidence during chemotherapy. No significant pre-chemotherapy differences were noted in inflammatory or intestinal barrier markers (P > 0.05). Throughout the course of treatment, we observed a reduction in inflammatory markers in both groups (P < 0.05), with the experimental group showing more significant declines. Intestinal barrier functions degraded over time in both groups, with more significant reductions in the study group (P < 0.05). The therapy combining significantly mitigates inflammation, bolsters intestinal and immune functions, and alleviates diarrhea in CCP. Clinical Registration: The authors have nothing to report.

A subset of cancer patients receiving monoclonal antibody PD-1/PD-L1 inhibitors may develop immune checkpoint inhibitor (ICI)-related neurological complications, such as ICI-related myasthenia gravis(MG)-myositis overlap syndrome and ICI-related myocarditis. Standard management typically involves intravenous immunoglobulin (IVIG), plasma exchange (PE), and high-dose corticosteroids. The use of efgartigimod, a neonatal Fc receptor blocker, for the treatment of ICI-related MG-myositis overlap syndrome remains investigational, with only four relevant cases all representing overlap syndromes (MG with myositis, with or without myocarditis) - reported to date.

Immune checkpoint inhibitors (ICIs) can induce a broad spectrum of immune-related adverse events (irAEs), including rare fibroinflammatory autoimmune manifestations. IgG4-related disease (IgG4-RD) has only exceptionally been described following dual ICI therapy.