Venetoclax, a selective BCL-2 inhibitor, demonstrates efficacy in acute leukemia (AL) but variable pharmacokinetics. Therapeutic drug monitoring (TDM) may provide valuable pharmacologic insights for optimizing venetoclax therapy. This study explored the factors influencing plasma venetoclax concentrations and their correlation with febrile neutropenia (FN), aiming to establish predictive thresholds.

This study presents a preliminary investigation into the antimicrobial, antibiofilm, and antiproliferative potential of Eremothecium coryli, an endophytic fungus isolated from the seeds of Basella alba L. The biological activities were evaluated using a crude extract-based screening study, employing the lyophilized cell-free supernatant (LCFS) of the fungal culture. Antibacterial and antibiofilm activities were assessed against selected multidrug-resistant bacterial pathogens, while antiproliferative activity was evaluated against breast cancer cell lines and a normal breast epithelial cell line. The LCFS demonstrated measurable antibacterial activity and significant biofilm-inhibition in a concentration-dependent manner. In cytotoxicity assays, selective growth inhibition of breast cancer cell lines was observed when compared with normal cells. Chemical profiling using Liquid Chromatography-Mass Spectrometry and Gas Chromatography-Mass Spectrometry enabled putative metabolite identification, revealing the presence of compounds previously reported to exhibit antimicrobial and anticancer activities. However, these identifications are tentative and based on spectral library matching. Overall, this preliminary investigation highlights the biological potential of E. coryli-derived metabolites. Further purification and validation are necessary to confirm compound identities, elucidate mechanisms of action, and assess in vivo relevance.

Immune checkpoint inhibitors-induced diabetes mellitus (ICI-DM) is a rare but potentially life-threatening endocrine immune-related adverse event, often characterized by abrupt onset of insulin deficiency and frequent presentation with diabetic ketoacidosis and difficulty with daily management with the available therapies. Lung cancer patients represent a substantial proportion of reported cases, reflecting the widespread use of PD-1/PD-L1 inhibitors in thoracic oncology. We report on the case of an elderly patient with metastatic lung adenocarcinoma treated with pembrolizumab who developed severe DM requiring permanent insulin therapy and leading to treatment discontinuation. The patient was subsequently followed over a prolonged period, during which oncological disease remained under sustained control despite immunotherapy interruption. We describe the clinical course, diagnostic workup, and multidisciplinary management, and review current guideline recommendations addressing acute metabolic management, diabetic treatment, and decision-making regarding continuation of immunotherapy. This case highlights the complexity of managing ICI-DM in real-world clinical practice. The current guidelines may help in broad terms. Although guidelines have been published, they remain cursory. Nevertheless, therapeutic decisions should ultimately be individualized through close multidisciplinary collaboration.

Parasite-derived molecules have emerged as a promising source of natural bioactive compounds with immunomodulatory and antitumor properties, attracting increasing attention in cancer research. Derived from both protozoan and helminth parasites, these molecules exhibit diverse biological activities that extend beyond parasite survival and represent a novel resource for cancer therapy. Accumulating evidence demonstrates that parasite-derived molecules suppress tumor progression through complementary immune-mediated and non-immune mechanisms, including activation of innate and adaptive antitumor immunity, remodeling of the tumor microenvironment, induction of apoptosis and autophagy, inhibition of angiogenesis and metastasis, and regulation of tumor metabolism. Recent preclinical studies have demonstrated encouraging therapeutic efficacy across multiple tumor models, including melanoma, lung cancer, colorectal cancer, breast cancer, hepatocellular carcinoma, and other malignancies. In addition to summarizing the major classes of parasite-derived molecules and their mechanisms of action, this review highlights recent advances in translational research, including combination therapeutic strategies, immunogenicity and safety, delivery system optimization, and manufacturing and regulatory considerations. Despite encouraging preclinical findings, substantial challenges remain before clinical translation can be achieved. By integrating current mechanistic evidence with emerging translational perspectives, this review provides a comprehensive overview of parasite-derived molecules as potential anticancer agents and offers insights to facilitate their future development and clinical application in cancer therapy.

Malignancy remains a major cause of late morbidity and mortality in kidney transplant recipients, largely due to chronic immunosuppression and impaired tumor immune surveillance. Mammalian target of rapamycin inhibitors have antiproliferative and antiangiogenic properties and are frequently used in recipients considered to be at increased oncologic risk. However, their protective effect against de novo malignancy is not absolute. Here, we report 2 cases of severe malignancies that developed in kidney transplant recipients after conversion from calcineurin inhibitors to sirolimus following polyomavirus-associated nephropathy. The first patient, a 55-year-old man, developed prostate adenocarcinoma 6 years after transplant and 4 years after conversion to sirolimus. The diagnosis was established during evaluation for severe anemia and graft dysfunction. The second patient, a 35-year-old woman, developed primary central nervous system posttransplant lymphoproliferative disorder 4 years after transplant and 2 years after conversion to sirolimus. Histopathologic examination confirmed an aggressive lymphoma without detectable Epstein-Barr virus infection. These cases illustrate that mammalian target of rapamycin inhibitor-based immunosuppression does not eliminate the risk of solid or hematologic malignancy. Cumulative immunosuppressive exposure, viral complications, and delayed conversion may contribute to persistent oncogenic risk. Careful long-term oncologic surveillance and individualized immunosuppressive management remain essential in kidney transplant recipients.

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.

Lung cancer remains the leading cause of cancer-related mortality worldwide, with lung adenocarcinoma (LUAD) being its most prevalent histological subtype, which is plagued by severe drug resistance and dismal long-term survival. Current treatment approaches are often limited by drug resistance and metastasis. Ferroptosis, an iron-dependent form of regulated cell death driven by lipid peroxidation, represents a promising novel therapeutic target to address these unmet clinical needs.

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.

Currently, PARP inhibitors (PARPis) have been primarily utilized to treat ‌breast cancer susceptibility gene (BRCA)-mutated triple-negative breast cancer (TNBC), but their application scope is quite narrow. Recently, it has been discovered that suppression of phosphoinositide 3-kinase/protein kinase B/mammalian target of rapamycin (PI3K/AKT/mTOR) signaling pathway sensitizes BRCA-proficient TNBC to PARPis. In the study, a new PARP inhibitor DA1, modulating PI3K/AKT/mTOR pathway, was designed and synthesized. DA1 showed good antiproliferative effects on BRCA-proficient TNBC cells MDA-MB-231, BT549 and MDA-MB-468, with IC50 values of 0.77 ± 0.03, 1.33 ± 0.01 and 0.28 ± 0.02 μM, respectively. Moreover, DA1 potently inhibited PARP-1 and PARP-2, with IC50 values of 2.5 ± 0.8 and 1.4 ± 0.5 nM respectively. Mechanistically, DA1 suppressed the PI3K/AKT/mTOR signaling pathway, increased DNA damage, caused cell cycle arrest in G2/M phase, and accelerated MDA-MB-231 apoptosis. Additionally, DA1 efficiently suppressed MDA-MB-231 cell migration and invasion. It also exhibited remarkable anti-tumor activity in an MDA-MB-231 cell-derived xenograft model at a dose of 20 mg/kg, with significantly superior therapeutic effects compared to Olaparib, Tan IIA or the combo. Overall, DA1 presents a promising lead compound used to treat BRCA-proficient TNBC.

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.