Search Results (395)

The concept of “platinum sensitivity” has long guided prognostic assessment and treatment selection in recurrent ovarian cancer. However, the emergence of targeted agents, such as bevacizumab and poly (ADP-ribose) polymerase inhibitors, has complicated its clinical utility. In contrast, emerging evidence suggests that platinum sensitivity may also be applicable to recurrent endometrial cancer. As in ovarian cancer, a prolonged platinum-free interval (PFI) in recurrent endometrial cancer is associated with an improved efficacy of subsequent platinum-based chemotherapy. The PFI is linearly correlated with the response rate to platinum re-administration, progression-free survival, and overall survival. Patients are typically classified as having platinum-resistant or platinum-sensitive disease based on a PFI cutoff of 6 or 12 months. However, unlike in ovarian cancer—where the duration of response to second-line platinum-based chemotherapy rarely exceeds the prior PFI (~3%)—approximately 30% of patients with recurrent endometrial cancer exhibit a sustained response to platinum rechallenge that extends beyond their preceding PFI. Despite the incorporation of immune checkpoint inhibitors into the treatment landscape of endometrial cancer, the role of platinum sensitivity in clinical decision-making—particularly regarding treatment sequencing and drug selection—remains a critical and unresolved issue. Further research is warranted to elucidate the mechanisms underlying platinum resistance and to guide optimal therapeutic strategies. Full article

The development of novel platinum-based anticancer agents remains a critical objective in medicinal inorganic chemistry, particularly in light of resistance and toxicity limitations associated with cisplatin. In this study, the synthesis, structural characterization, quantum chemical analysis, and cytotoxic evaluation of four new acetylplatinum(II) complexes (cis-[Pt(COMe)₂(PASO₂)₂], cis-[Pt(COMe)₂(DAPTA)₂], trans-[Pt(COMe)Cl(DAPTA)₂], and trans-[Pt(COMe)Cl(PASO₂)]: 1–4, respectively) bearing cage phosphine ligands PASO₂ (2-thia-1,3,5-triaza-phosphaadamantane 2,2-dioxide) and DAPTA (3,7-diacetyl-1,3,7-triaza-5-phosphabicyclo[3.3.1]nonane) are presented. The coordination geometries and NMR spectral features of the cis/trans isomers were elucidated through multinuclear NMR and DFT calculations at the B3LYP/6-311++G(d,p)/LanL2DZ level, with strong agreement between experimental and theoretical data. Quantum Theory of Atoms in Molecules (QTAIM) analysis was applied to investigate bonding interactions and assess the covalent character of Pt–ligand bonds. Cytotoxicity was evaluated against five human cancer cell lines. The PASO₂-containing complex in cis-configuration, 1, demonstrated superior activity against thyroid (8505C) and head and neck (A253) cancer cells, with potency surpassing that of cisplatin. The DAPTA complex 2 showed enhanced activity toward ovarian (A2780) cancer cells. These findings highlight the influence of ligand structure and isomerism on biological activity, supporting the rational design of phosphine-based Pt(II) anticancer drugs. Full article

Cisplatin was the first metal-based anticancer drug introduced into clinical use. It is a “small” molecule, but it represented a very “big” discovery. Since it was introduced on the market, it has not been withdrawn, despite being not free of side effects, owing to its peculiarity of being highly effective in the treatment of cancer. Anticancer activity of the platinum-based complexes was discovered with this molecule; since then, several other platinum-based drugs have been developed and tested in preclinical studies against cancer cells; however, only a few of them reached clinical trials, and their side effects are not much less than cisplatin. Despite the constraints of drug resistance and side effects, chemotherapy remains a fundamental strategy in cancer treatment. Nowadays, cisplatin remains one of the most-used anticancer agents in treating lung, colon, ovary, testicles, bladder, cervix, and many more cancers, although cisplatin resistance represents a major hurdle in cancer treatment. Will there ever be another drug that can overcome the side effects of cisplatin but at the same time be able to block tumors as does cisplatin? Full article

Developments of nanostructured materials have a significant impact in various areas, such as energy technology and biomedical use. Examples include solar cells, energy management, environmental control, bioprobes, tissue engineering, biological marking, cancer diagnosis, therapy, and drug delivery. Currently, researchers are designing multifunctional nanodrugs that combine in vivo imaging (using fluorescent nanomaterials) with targeted drug delivery, aiming to maximize therapeutic efficacy while minimizing toxicity. These fascinating nanoscale “magic bullets” should be available in the near future. Inorganic nanovehicles are flexible carriers to deliver drugs to their biological targets. Most commonly, mesoporous nanostructured silica, carbon nanotubes, gold, and iron oxide nanoparticles have been thoroughly studied in recent years. Opposite to polymeric and lipid nanostructured materials, inorganic nanomaterial drug carriers are unique because they have shown astonishing theranostic (therapy and diagnostics) effects, expressing an undeniable part of future use in medicine. This review summarizes research from development to the most recent discoveries in the field of nanostructured materials and their applications in drug delivery, including promising metal-based complexes, platinum, palladium, ruthenium, titanium, and tin, to tumor cells and possible use in theranostics. Full article

Background: Nedaplatin is a platinum-based anticancer drug that combines the benefits of Cisplatin and Carboplatin, retaining Cisplatin’s anticancer activity while reducing toxicity similar to Carboplatin. After hydrolysis, Nedaplatin targets purines in DNA and forms cross-links that induce cell death via apoptosis. However, it is important to consider how the presence of other chemical compounds with structural similarities to Adenine or Guanine, such as aromatic, purine, or pyrimidine compounds containing a nitrogen atom with a free electron pair, might influence its activity at the cellular level. Alkaloids with structures similar to DNA nucleobases are common, and their influence on Nedaplatin’s activity requires investigation. Methods: In this study, the interactions between Nedaplatin (including its hydrolyzed forms, such as [Pt(NH₃)₂(H₂O)₂]²⁺ and [Pt(NH₃)₂(H₂O)(OH)]⁺) and nucleobases (Adenine and Guanine) and purine alkaloids (Caffeine, Theobromine and Theophylline) were thoroughly investigated using theoretical (density functional theory, DFT) and experimental (UV-Vis spectroscopy) methods. DFT calculations were performed at the B3LYP/6-31G(d,p)/LANL2DZ and MN15/def2-TZVP levels, with structure optimization and harmonic analysis in the gas phase and aqueous solution (modeled using IEF-PCM). UV-Vis spectroscopy was used to verify theoretical findings by examining changes in absorption spectra. Results: Both theoretical and experimental studies confirmed that Nedaplatin forms complexes with both nucleobases and purine alkaloids. Nedaplatin was found to exhibit a higher affinity for nucleobases than for purine alkaloids. Furthermore, this affinity was dependent on the computational method used and on the hydrolyzed form of Nedaplatin. Theoretical calculations showed the formation of stable complexes through bonding with nitrogen atoms in the ligand molecules, which was confirmed by changes in UV-Vis spectra, indicating adduct formation. Conclusions: The results indicate that Nedaplatin readily forms complexes with both nucleobases and purine alkaloids, showing a stronger affinity for nucleobases. This finding highlights the potential importance of Nedaplatin’s interactions with other compounds present in the body, which may influence its effectiveness and mechanism of action in cancer therapy. These studies provide new insights into the molecular mechanisms of Nedaplatin’s action and may contribute to a better understanding of its pharmacological interactions. However, research requires confirmation not only in in vivo studies but also in clinical trials. Full article

Ovarian cancer is the most lethal gynecologic malignancy, which causes 313,959 new cases and 207,252 deaths worldwide annually. The lack of specific symptoms, together with no effective screening tools, results in 75% of patients receiving their diagnosis at an advanced stage. The combination of cytoreductive surgery with platinum-based chemotherapy plays a pivotal role in the treatment of advanced epithelial ovarian cancer, but patients still experience poor long-term survival because of frequent relapses and chemotherapy resistance. The treatment landscape has evolved because bevacizumab and Poly-ADP Ribose Polymerase inhibitors now serve as frontline and maintenance therapies for homologous recombination-deficient tumors. Treatment decisions for recurrent disease depend on platinum sensitivity assessment, which determines the appropriate therapeutic approach, while targeted agents deliver significant benefits to specific patient groups. The development of antibody-drug conjugates such as mirvetuximab soravtansine and immunotherapy, including checkpoint inhibitors and cancer vaccines, demonstrates promising investigative potential. The precision of therapy improves through the use of emerging biomarkers and molecular profiling techniques. The future management of this disease may change because of innovative approaches that include adoptive cell therapy, cytokine therapy, and oncolytic viruses. The progress made in ovarian cancer treatment still faces challenges when it comes to drug resistance, survival improvement, and life quality preservation. The development of translational research alongside clinical trials remains essential to bridge treatment gaps while creating personalized therapies based on molecular and clinical tumor characteristics. Full article

Otorhinolaryngological (ORL) cancers, including malignancies of the oral cavity, pharynx, and larynx, show significant challenges in oncology. Cisplatin, a platinum-based chemotherapy drug, remains a cornerstone of treatment but is often limited by systemic toxicity and resistance. A comprehensive literature review was conducted using recent studies and clinical trials focused on nanotechnology-based cisplatin delivery systems. The analysis covered various types of nanocarriers, their mechanisms, and advantages. Additionally, the limitations of nanotechnology-based cisplatin delivery systems were discussed. Findings indicate that lipid-based nanoparticles, polymeric nanoparticles, inorganic nanoparticles, and extracellular vesicles have demonstrated improved drug targeting, bioavailability, and reduced systemic toxicity in preclinical and clinical studies. Nanocarriers also offer potential for overcoming drug resistance and enabling combination therapy. However, challenges related to biocompatibility, scalability, and regulatory approval remain significant barriers to widespread clinical adoption. Nanotechnology offers a novel and promising approach to optimizing cisplatin delivery for ORL cancers. While preclinical studies demonstrate significant potential, further research and clinical validation are essential to translate these advancements into routine clinical practice. Addressing manufacturing and regulatory challenges will be critical for future research. Full article

Background: Hyaluronicacid (HA)-conjugated nanocarriers leverage CD44 receptor overexpression on tumor cells for targeted delivery of platinum chemotherapeutics. Methods: This study compares non-functionalized (DDS1) versus HA-conjugated single-walled carbon nanotubes (DDS2) for encapsulation stability and CD44 binding of Cisplatin, Carboplatin, and Lobaplatin. Density Functional Theory calculations employed PBE-GGA with Tkatchenko–Scheffler dispersion and ZORA relativistic treatment, using a finite (8,8) armchair SWCNT (24.6 Å, H-capped) for DDS1 and an EDC/NHS-coupled HA oligomer for DDS2. We computed binding energies, HOMO–LUMO gaps, Molecular Electrostatic Potentials, and energy decompositions. Molecular docking to CD44 (PDB ID: 4PZ3) used Molegro Virtual Docker, validated by re-docking the native HA fragment (RMSD 1.79 Å). Results: DFT binding energies (eV) for DDS2 versus DDS1 were −7.92/−7.48 (Cisplatin), −8.93/−8.30 (Carboplatin), and −9.72/−9.25 (Lobaplatin), indicating enhanced stabilization by HA functionalization. Energy decomposition showed increases of ∼0.4 eV (vdW) and ∼0.2 eV (electrostatic) in DDS2. MEP maps confirmed additional negative-potential regions on DDS2, complementing drug-positive sites. Molecular docking yielded MolDock scores of −171.26 for DDS2 versus −106.68 for DDS1, reflecting stronger CD44 affinity. Docking scores indicate that HA conjugation notably strengthens the predicted affinity of CNT carriers toward the CD44 receptor ($\Delta$Score ≈ −65 kcal mol⁻¹). Conclusions: These results motivate experimental follow-up to confirm whether DDS2 can translate the in silico affinity gains into improved targeted delivery of platinum chemotherapeutics. Full article

Emergent cancer drug resistance and further metastasis can mainly be attributed to altered expression levels and functional activities of multiple genes of cancer cells under chemotherapy. In response to challenge with anticancer drugs, enhanced ceramide glycosylation catalyzed by glucosylceramide synthase (GCS) confers drug resistance and enrichment with cancer stem cells. p53 mutations, which gain function in tumor progression, are prevalently extant in ovarian cancers. Via integrated gene expression assessments, we characterized GCS-responsive genes in ovarian cancer cells treated with dactinomycin. NCI/ADR-RES cells dominantly expressed a p53 mutant (7 aa deleted in exon-5) and displayed anti-apoptosis; however, silencing GCS expression rendered these cells sensitive to dactinomycin-induced apoptosis. Microarray analyses of NCI/ADR-RES and its GCS transfected sublines found that elevated GCS expression or ceramide glycosylation was associated with altered expression of 41 genes, notably coding for ABCB1, FGF2, ALDH1A3, apolipoprotein E, laminin 2, chemokine ligands, and IL6, with cellular resistance to induced apoptosis and enrichment with cancer stem cells, promoting cancer progression. These findings were further corroborated through integrated genomic analyses of ovarian cancer from The Cancer Genome Atlas (TCGA) and cancer resistance to platinum-based chemotherapy. Altogether, our present study indicates that altered ceramide glycosylation can modulate expression of these GCS-responsive genes and alter cancer cell attributes under chemotherapy. Full article

In this study, a novel 4-methylbenzoylhydrazide·dimethyl sulfoxide·dichloro platinum(II) complex (Pt2) was synthesized and characterized, and its anti-tumor activity and action mechanism were explored. The molecular structure and spatial configuration of the complex were determined using X-ray diffraction. The results obtained using fluorescence spectroscopy demonstrate that this complex can effectively bind to DNA and affect its fluorescence properties. The experimental results show that Pt2 exhibited significant inhibitory effects on a variety of tumor cell lines (MCF-7, HepG-2, NCI-H460, T24, and A549), and its IC50 values were lower than those of cisplatin (DDP), indicating stronger anti-tumor activity. In addition, the complex not only significantly induced the apoptosis of MCF-7 cells but also inhibited cell cycle arrest at the G₂ phase, with the proportion of G₂-phase cells as high as 49.47%. In conclusion, the 4-methylbenzoylhydrazide platinum(II) complex exhibits good anti-tumor activity by inducing apoptosis and inhibiting the cell cycle, providing an important experimental basis for the development of novel platinum-based anti-tumor drugs. Full article

Background: Docetaxel is the standard of care for advanced non-small cell lung cancer (NSCLC) after platinum-based chemotherapy and/or immunotherapy but is associated with modest clinical outcomes and considerable toxicity. Sacituzumab govitecan and datopotamab deruxtecan are trophoblast cell surface antigen (TROP)-2-directed antibody–drug conjugates (ADCs) that showed encouraging activity in pretreated patients with advanced NSCLC. This systematic review and pooled analysis aims to comprehensively assess the efficacy and safety of anti-TROP-2 ADCs compared to docetaxel in pretreated patients with advanced NSCLC. Methods: A systematic search through PubMed and EMBASE before 31 January 2025 was performed to identify eligible studies. Randomized controlled phase III trials comparing an anti-TROP-2 regimen to docetaxel in patients with pretreated advanced NSCLC were included. Overall survival (OS), progression-free survival (PFS), and grade ≥ 3 treatment-related adverse events (TRAEs) were extracted from the identified trials. A pooled analysis of reconstructed patient data and meta-analysis employing the random-effect model were used to summarize the efficacy and safety outcomes. Results: Across the two trials included, 1207 patients were enrolled, 598 in the TROP-2 ADC arm and 609 in the docetaxel arm. Anti-TROP-2 treatment did not produce significant improvements in OS (HR: 0.90; 95% CI, 0.78–1.03; P = 0.13) and PFS (HR: 0.84; 95% CI, 0.68–1.02; P = 0.08), compared to docetaxel, even in patients with a nonsquamous histology (OS HR: 0.86; 95% CI, 0.73–1.01; P = 0.06; PFS HR: 0.76; 95% CI, 0.52–1.12; P = 0.17). Across the subgroup analyses, a statistically significant improvement in OS was observed in patients with actionable genomic alterations (AGAs) (HR: 0.63; 95% CI, 0.41–0.95; P = 0.03). Compared to docetaxel, the anti-TROP-2 regimen demonstrated a lower risk of developing grade ≥ 3 TRAEs (RR: 0.76; 95% CI, 0.55–1.05; P = 0.09). Conclusions: The anti-TROP-2 regimen showed a better safety profile but failed to demonstrate a relevant clinical improvement over docetaxel. Anti-TROP-2 ADCs could find a role in the management of patients with AGAs. Full article

Background: Niraparib is an oral poly (adenosine diphosphate-ribose) polymerase inhibitor with promising activity for patients with advanced breast cancer harboring germline BRCA1/2 mutations. Methods: LUZERN (NCT04240106) was a multicenter, open-label, Simon’s two-stage, phase II clinical trial evaluating the efficacy and safety of niraparib with aromatase inhibitors (AIs) for patients with HR-positive/HER2-negative advanced breast cancer with either a germline BRCA1/2 mutation (cohort A) or germline BRCA1/2 wild-type and homologous recombination deficiency (exploratory cohort B). Eligible patients received ≤1 line of chemotherapy and 1–2 prior lines of endocrine therapy for advanced disease with secondary resistance to the last AI-based regimen. Patients received niraparib (300 mg or 200 mg) plus an AI. The primary endpoint was the clinical benefit rate (CBR) in cohort A. Results: Between June 2020 and November 2022, 14 patients were enrolled in cohort A (n = 6 for stage I, n = 8 for stage II) and no patients were enrolled in cohort B. One patient was excluded from the efficacy analysis due to no prior AI treatment. Nearly all patients (92.9%) previously received a cyclin-dependent kinase 4/6 inhibitor, but no patients had received prior platinum-based chemotherapy. Median follow-up was 16.7 months (range: 13.2–18.2). The CBR was 46.2% (95% CI: 19.2–74.9), meeting the primary endpoint. Median progression-free survival was 5.5 months (95% CI: 1.9–8.5), and median overall survival was 18.1 months (95% CI: 9.7–NE). The safety profile was consistent with the known toxicity of both drugs. Conclusions: Niraparib combined with an AI has encouraging antitumor activity and a manageable safety profile in patients with AI-resistant HR-positive/HER2-negative advanced breast cancer with germline BRCA1/2 mutations. Full article

Nucleoside reverse transcriptase inhibitors (NRTIs) and platinum-based chemotherapeutics are widely utilized in cancer treatment. Evidence suggests that drug plasma concentrations are closely linked to both therapeutic efficacy and the risk of adverse effects. Consequently, developing therapeutic drug monitoring (TDM) methods is essential. Here, an effective procedure utilizing QuEChERS (Quick, Easy, Cheap, Effective, Rugged, and Safe) techniques for preparing samples and UPLC-MS/MS for simultaneously measuring eight NRTIs and platinum-based drugs in human plasma is described. Chromatographic separation was conducted with an Agilent Eclipse Plus C18 column (4.6 × 100 mm, 3.5 μm) with acetonitrile with 0.1% formic acid as Phase A and 0.1% formic acid in water as Phase B, achieving complete separation within 10 min. The target analytes—lamivudine, telbivudine, emtricitabine, entecavir, tenofovir, nedaplatin, oxaliplatin, and adefovir dipivoxil—exhibited strong linearity within the 10–1000 ng/mL and 1–100 ng/mL ranges, showing correlations (r²) ≥ 0.9962. The method demonstrated excellent accuracy (−6.72% to 7.82%) and selectivity (84.53%–110.49%), as well as satisfactory recovery and stability. Overall, this analytical approach can be used to detect the combination of eight NRTIs and platinum-based drugs in human plasma. This method enables plasma drug-level monitoring in real time, with applications for individualized treatment approaches. Full article

Lung adenocarcinoma (LUAD) is a leading cause of cancer-related mortality, with heme metabolism playing a critical role in tumor progression and treatment resistance. This study investigates the clinical implications of heme metabolism in LUAD, focusing on its link to ferroptosis and drug sensitivity. Using multi-omics data from TCGA-LUAD, GEO databases, and a single-cell RNA-seq cohort, we identified two molecular subtypes based on heme metabolism-related genes. We further developed a prognostic panel, termed the heme metabolism risk score (HMRS), using LASSO and multivariate Cox regression analyses. The HMRS panel effectively stratified patients into high- and low-risk groups, with high-risk patients showing enhanced tumor proliferation, suppressed ferroptosis, and resistance to chemotherapy. Single-cell analysis revealed elevated heme metabolism risk in epithelial cells correlated with tumor progression. Drug sensitivity predictions were validated in platinum-based chemotherapy cohorts, confirming HMRS as a robust prognostic tool. ABCC2 was identified as a key regulator of ferroptosis and cisplatin resistance, with in vitro experiments demonstrating that ABCC2 knockdown enhanced cisplatin-induced ferroptosis. These findings highlight HMRS as a critical tool for patient stratification and ABCC2 as a promising therapeutic target to overcome cisplatin resistance. Full article

Microphysiological systems (MPS) incorporating microfluidic technologies offer improved physiological relevance and real-time analysis for cell-based assays, but often lack non-invasive monitoring capabilities. Addressing this gap, we developed a microfluidic cell-based assay platform integrating an electrochemical biosensor for real-time, non-invasive monitoring of kinetic cell status through glucose consumption. The platform addresses the critical limitations of traditional cell assays, which typically rely on invasive, discontinuous methods. By combining enzyme-modified platinum electrodes within a microfluidic device, our biosensor can quantify dynamic changes in glucose concentration resulting from cellular metabolism. We have integrated a calibration function that corrects sensor drift, ensuring accurate and prolonged short-term measurement stability. In the validation experiments, the system successfully monitored glucose levels continuously for 20 h, demonstrating robust sensor performance and reliable glucose concentration predictions. Furthermore, in the cell toxicity assays using HepG2 cells exposed to varying concentrations of paraquat, the platform detected changes in glucose consumption, effectively quantifying the cellular toxicity responses. This capability highlights the device’s potential for accurately assessing the dynamic physiological conditions of the cells. Overall, our integrated platform significantly enhances cell-based assays by enabling continuous, quantitative, and non-destructive analysis, positioning it as a valuable tool for future drug development and biomedical research. Full article