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.

Hepatocellular carcinoma (HCC) is a highly refractory malignancy, for which treatment relies on molecule targeted therapy and/or conventional chemotherapy in clinic. However, these approaches generally suffer from limited efficacy or severe toxicity, restricting their applications. Guided by the targeted drug conjugate (TDC) strategy, the pharmacophore of lenvatinib was modified by incorporating DN604 (C6H10N2O5Pt), a carboplatin analogue, to generate a Pt(II) complex Len-604 (C30H33ClN8O9Pt). This compound was found to possess the specific capability to bind to fibroblast growth factor receptor 4 (FGFR4) protein both in vitro and in vivo, facilitating targeted delivery of DN604 to tumor sites and consequently triggering serious DNA damage in cancer cells. It exhibited potent cytotoxicity against human hepatocellular carcinoma cell lines HUH-7 and SMMC-7721, with IC50 values of 5.62 and 5.64 μM, respectively. Significantly, in HUH-7 xenograft models, Len-604 exhibited stronger antitumor activity than lenvatinib, while showing lower toxicity than cisplatin and its physical mixture with lenvatinib.

The structural diversity of natural products provides a major source for discovering antimicrobials with novel structures or mechanisms to overcome microbial resistance. Herein, we prepared a series of rutaecarpine-pyridinium quaternary ammonium conjugates by using rutaecarpine as the lead compound. Bioactivity evaluation demonstrated that 5dl exhibits outstanding antibacterial activity against S. aureus ATCC 29213 and clinical MRSA isolates, with MIC values ranging from 0.5 to 2 μg/mL, comparable to vancomycin. Low hemolysis, low resistance frequency, low cytotoxicity, rapid bactericidal properties, and good plasma stability indicate the further application potential of 5dl. Notably, 5dl exhibited better therapeutic efficacy than vancomycin in two mouse models of MRSA infection. Mechanistic studies revealed that 5dl not only targetingly disrupts the MRSA cell membranes but also inhibits Topo I activity, thereby interfering with DNA replication and transcription processes, ultimately leading to MRSA cell death. These findings demonstrate that 5dl could serve as a promising candidate for combating MRSA infections.

Near-infrared (NIR) light-responsive nanomaterials have emerged as powerful tools for cancer therapy, yet stable and biocompatible delivery of NIR-II agents remains a major challenge. In this work, we develop NIR-I/II-responsive niosomes co-encapsulating plasmonic gold nanorods (GNRs) and the NIR-II dye, IR1061, forming a multifunctional nanoplatform for effective phototherapeutic ablation of cancer cells. The niosomal system provides robust encapsulation, improved dispersion stability, and biocompatibility for both photoactive components. Upon NIR-I/II laser irradiation, the nanoplatform exhibits strong photothermal heating and substantial reactive oxygen species generation due to the synergistic integration of plasmonic GNRs and dye-mediated effects. In vitro evaluations demonstrate efficient cellular uptake, potent photoinduced cytotoxicity, and minimal dark toxicity. The integration of photothermal and photodynamic mechanisms results in markedly enhanced therapeutic efficacy compared with individual agents. This study highlights the potential of niosomes as versatile and efficient nanocarriers for dual NIR-window phototherapy, offering a promising route for precise and minimally invasive cancer treatment.

Although routine treatment methods aim to aggressively destroy tumour tissues, they often fail to account for the correlations of tissue destruction and regeneration processes. Despite considerable progress in the field of oncology, it is worth noting the ancient ways of treatment using products from nature which potentially can effectively support current therapies.

Over the past decade, antibody-drug conjugates (ADCs) have emerged as promising anti-cancer therapeutics, with twelve ADCs approved by the FDA. This review evaluates trends in these ADCs, stratified by payloads on doses studied from first-in-human (FIH) trials through approval and post-marketing. It summarizes trends in pharmacokinetics (PK), drug-drug interactions (DDI), exposure-response analysis, immunogenicity, and organ impairment. Additionally, it provides perspectives on potential postmarketing requirements associated with clinical pharmacology attributes, and how this knowledge could inform efficient early clinical development of newer ADCs. Except for sacituzumab govitecan, which had a starting dose of 8 mg/kg, starting doses of ADCs ranged from 0.0067 to 0.8 mg/kg. All ADCs have been administered intravenously. Dose escalation generally progressed over four to eight distinct levels, with increments of 20% to 233% at the first three levels. The maximum tolerated dose was achieved by the fourth to seventh dose level in most cases. For 5/12 ADCs, the recommended phase 2 dose and the phase 3 dose were the same as the MTD. Approved doses ranged from 1.25-fold to 40-fold higher than the FIH starting dose levels. Generally, ADCs exhibited dose-proportional PK within the tested dose range. Exposure-response relationships have been reported for ADC/total antibody for efficacy and ADC/total antibody/payload exposures for safety. DDI potential has been reported for payloads associated with auristatins, maytansinoids, and camptothecin: SN38. At approved doses, immunogenicity assessments indicated low incidence of anti-drug antibodies. Organ impairment studies suggest no significant risk in patients with moderate hepatic or renal impairment.

Herein, we described the design and synthesis of a series of melampomagnolide B-dithiocarbamate hybrids and the evaluation of their anti-lung cancer activities. The most active compound 86 (IC50 = 0.46 μM) exhibited a highly potent inhibitory effect on NCI-H820 cells, with a 44-fold increase compared to the natural product melampomagnolide B (IC50 = 20.43 μM). Compound 86 mediated mitochondrial dysfunction, promoted ROS generation to disrupt redox homeostasis, and eventually induced apoptosis, ferroptosis, and cuproptosis in lung cancer cells in vitro and in vivo. Preliminary toxicity assessment indicated that compound 92, the water-soluble prodrug of 86, exhibited no apparent toxicity. Furthermore, 92 significantly reduced the tumor volume and tumor weights in lung cancer CDX and PDX models. These findings suggested that 92 deserved further studies as a potential candidate for the ultimate discovery of effective anti-lung cancer agents.

Cisplatin (CDDP) resistance is a major obstacle in the management of advanced and recurrent gastric cancer (GC). An in-depth analysis of signaling pathways involved in GC cell phosphorylation could help to identify critical pathways linked to CDDP resistance. Our research aimed to investigate the molecular mechanisms and clinical implications of the role of 14-3-3β in GC CDDP resistance. We established an AGS cell line that was resistant to CDDP, and used this, along with AGS and HGC-27 cell lines, as well as subcutaneous xenografts in nude mice, to create in vitro and in vivo models for our functional experiments. To highlight the clinical significance, we also examined a cohort of 127 gastric cancer patients who underwent treatment with platinum drugs. The results indicated that the proteome regulated by 14-3-3β, along with its phosphorylated alterations, may contribute towards CDDP resistance in GC cells. It is noteworthy that 14-3-3β governs a distinct phosphorylation modification system by regulating various tumor-associated molecules, such as EGFR, Akt, MEK1, and NFκB-p65. Concurrently, upregulated 14-3-3β expression induced the phosphorylation of Hsp90B, thus facilitating CDDP resistance. Consequently, silencing 14-3-3β significantly improved CDDP sensitivity in vivo. An immune-histochemistry panel further disclosed that elevated expression of both 14-3-3β and p-Hsp90B correlated with worse survival, compared to all other combinations observed. Our study suggests that 14-3-3β modulates the phosphorylated alterations of the cancer-related proteome. Unveiling the role of the 14-3-3β/Hsp90B pathway in GC CDDP resistance implies it could serve as a potential therapeutic target for treating CDDP-resistant GC patients.

Breast cancer progression depends on abnormal angiogenesis, driven by VEGF/VEGFR2/ERK and inhibited by Angiotensin-Converting Enzyme 2 (ACE2). Chrysophanol (CHR) shows anti-breast cancer efficacy, but its mechanism is unclear.

The use of immune checkpoint inhibitors (ICIs) has expanded substantially across tumor types, establishing them as a cornerstone of modern oncology. However, the frequency and severity of immune-related adverse events (irAEs) remain underestimated, particularly hematologic toxicities, which can be life-threatening and require distinct management approaches compared to cytotoxic or targeted therapies.

The clinical utility of anthracyclines is limited by severe cardiotoxicity and multidrug resistance (MDR) necessitates the development of improved analogues and new chemotherapeutics. In this work a series of 2-substituted 4,11-diaminoanthra[2,3-b]furan-5,10-diones (anthrafurans) was synthesized via Pd-catalyzed cross-coupling/heterocyclization followed by the amination reaction. Several derivatives demonstrated low submicromolar cytotoxicity against five tumor cell lines comparable to doxorubicin and reduced cytotoxicity toward non-cancerous cells. Structure-activity relationship analysis demonstrated that hydrophobic 2-substituents (phenyl, trimethylsilyl) and N-methylated aminoalkyl side chains at the 4,11-positions enhanced potency and effectively circumvented Pgp- and p53-mediated MDR, while hydrophilic groups (hydroxymethyl, aminomethyl) decreased activity. Mechanistic studies showed that the 2-phenyl derivative 2b acts as a DNA-intercalating dual topoisomerase I and II inhibitor, causing DNA damage and apoptosis in leukemia cells, whereas the 2-aminomethyl analog 2j displayed weaker cellular activity due to poor intracellular accumulation despite similar in vitro DNA and topoisomerase interactions. None of the tested compounds generated significant reactive oxygen species, suggesting low oxidative stress and potentially reduced cardiotoxicity. Overall, the 4,11-diaminoanthra[2,3-b]furan-5,10-dione scaffold represents a promising and tunable platform for next-generation anthraquinone-based anticancer agents, offering potent antiproliferative activity, improved safety profile, and the ability to overcome MDR mechanisms.

Current cancer immunotherapies are often limited by suboptimal efficacy and significant adverse effects. Strategies centered on immunogenic cell death (ICD) offer promising solution, yet monotherapies frequently fail to achieve complete tumor eradication. To address this, we developed an alginate-based hydrogel system (SA-NLG-NA-DOX) for the co-delivery of an immunomodulator, a tumor vaccine, and the chemotherapeutic drug doxorubicin. This platform enabled sustained drug release and elicited potent, broad-spectrum cytotoxicity against multiple tumor cell lines. Furthermore, it robustly activated dendritic cells, enhancing their phagocytic capacity and stimulating the secretion of key inflammatory cytokines. The underlying immune activation was mechanistically linked to the cGAS-STING and TLR-MyD88 pathways. Collectively, SA-NLG-NA-DOX represents a novel and translatable chemo-immunotherapy platform with significant potential for improved cancer treatment.

The predictive value of programmed death-ligand 1 (PD-L1) expression for nivolumab efficacy in head and neck squamous cell carcinoma (HNSCC) remains controversial, partly due to variability among antibody clones. This study compared the SP142 and 28-8 PD-L1 antibody clones using multiple scoring systems to identify the most informative parameters for predicting nivolumab efficacy.

In the current medical era, developing multi-target anticancer agents that simultaneously engage complementary cellular vulnerabilities represents a promising strategy to overcome the inherent limitations of single-target therapeutics. Building on insights from our previous investigation, we synthesized a novel series of coumarin-pyrazolo [1,5-a]pyrimidine hybrids (13a-n) designed to target tumor-associated carbonic anhydrases (CA IX/XII) and tubulin polymerization through rational molecular hybridization. Structure-activity relationship analysis revealed that a zinc-binding sulfonamide group was essential for CA inhibitory activity; coumarin-only analogs failed (Ki > 100 μM). Compounds 13g and 13n, bearing sulfonamide functionality, demonstrated nanomolar potency against hCA IX and hCA XII. Compound 13n emerged as the superior lead, achieving balanced dual-target inhibition: hCA IX (Ki = 27.1 nM), hCA XII (Ki = 20.9 nM), and tubulin polymerization (IC50 = 6.35 μM). Broad-spectrum NCI-60 screening revealed 13n's potent antiproliferative activity across nine cancer types (GI50: 2.48-31.00 μM). Treatment of MCF-7 breast cancer cells with 13n resulted in significant G2/M phase arrest (13.81% to 31.97%) and robust induction of apoptosis (37-fold relative to control), mediated by p53-dependent signaling. Molecular analysis revealed elevated p53 expression (3.43-fold), increased Bax level (12.34-fold), reduced Bcl-2 expression (4.37-fold), and enhanced caspase-7 activation (7.35-fold). Molecular docking studies confirmed zinc coordination within the CA active sites and optimal positioning within the tubulin colchicine-binding pocket. In summary, compound 13n validates the design strategies employed to develop an efficient multi-target anticancer candidate, positioning this lead compound for further preclinical development.

A series of novel benzimidazole-based thioamide derivatives were designed, synthesized, and evaluated for their anticancer potential, supported by EGFR-targeted molecular docking studies. The synthetic strategy involved a base-mediated nucleophilic substitution reaction between 1-(substitutedphenyl)-2-((5-(difluoromethoxy)-1H-benzo[d]imidazol-2-yl)thio)ethan-1-one intermediate (1) and brominated nitrobenzyl derivative (2), enabling efficient CC bond formation at the C5 position of the benzimidazole ring. Reaction parameters were systematically optimized, including solvent, base, and temperature, wherein acetonitrile as solvent and potassium carbonate as base under reflux conditions afforded the best yields. Under optimized conditions, a library of ten derivatives was synthesized and fully characterized using NMR spectroscopy. The synthesized compounds were evaluated for in vitro cytotoxic activity against three human cancer cell lines: MCF7 (breast), A-549 (lung), and HEP-G2 (liver). Several derivatives exhibited promising anticancer activity, with compound 6-8b emerging as the most potent, displaying IC₅₀ values of 3.70 μM against A-549 and 5.38 μM against HEP-G2 cells. Molecular docking studies against the T790M-mutated EGFR kinase domain (PDB ID: 2JIV) revealed favorable binding interactions, superior docking scores, and binding energies compared to the reference inhibitor Neratinib. ADME predictions were made using Qikprop. These derivatives may represent a preliminary lead scaffold warranting further mechanistic validation and structural optimization; however, experimental confirmation of EGFR target engagement is required before definitive anticancer claims can be made.

Cyclin-dependent kinase 2 (CDK2) and vascular endothelial growth factor receptor 2 (VEGFR2) are essential for the development of tumor angiogenesis and the cell cycle, respectively. Inhibiting both kinases at the same time has therefore become a sensible anticancer tactic. A number of unique hybrid compounds containing isatin-triazole and isatin-imidazole scaffolds were created and thoroughly described in an effort to find dual CDK2/VEGFR2 inhibitors. Compounds 5d, 5k, and 10 showed the strongest antiproliferative activity against breast (MCF7) and prostate (PC3) cancer cell lines among the produced derivatives. Notably, compound 10 showed the most inhibitory potency, with IC50 values of 0.058 μM for VEGFR2 and 0.789 μM for CDK2, respectively. These values are on par with or higher than those of the reference standards, roscovitine and sunitinib. Additionally, a biological study showed that compounds 5d and 5 k had negligible off-target toxicity and were selectively lethal to cancer cells compared to normal HaCaT keratinocytes. Furthermore, cell cycle studies revealed that compound 5d produced S-phase arrest, whereas compounds 5 k and 10 mostly caused G-phase arrest, in line with their kinase inhibition profiles. Additionally, the potent analogues 5d and 10 substantially decreased colony formation and tumoral cell migration. Molecular docking and dynamics simulations helped to clarify the possible binding interactions inside the ATP-binding sites of CDK2 and VEGFR2, confirming the dual-binding mechanism that underlies their potent effects. According to all of these findings, compound 10 is a potential dual CDK2/VEGFR2 inhibitor that offers a helpful foundation for the development and optimization of future multitarget anticancer agents.

This investigation explores the thermal resistance and degradation behaviour of silver nanoparticles (AgNPs). Additionally, the study demonstrated the catalytic effectiveness of biogenic AgNPs, produced through an eco-friendly approach utilizing aqueous extract from Mikania micrantha leaf extract, for the efficient construction of a variety of 2,4,5-triphenyl-1H-imidazole compounds in reaction times ranging from 30 to 180 s. The synthesized products were thoroughly characterized employing spectroscopic techniques, including FTIR, 1H NMR, 13C NMR, and mass spectrometry. Furthermore, the antimicrobial efficacy of the biogenic AgNPs was systematically evaluated against Staphylococcus aureus, Bacillus cereus, Yersinia pestis, and Streptococcus enterica using nutrient agar as the growth medium. The findings indicated that green-synthesized AgNPs, as well as Mikania micrantha, demonstrated antibacterial activity against all tested strains, with B. cereus showing the minimum inhibition zone (15 ± 0.2 mm) and (12 ± 0.1), Y. pestis displaying the maximum inhibition zone (21 ± 0.3 mm) and (17 ± 0.4 mm), respectively. In addition, both the plant extract and the AgNPs were assessed for cytotoxicity against the human colon carcinoma cell line (Caco-2) using the MTT assay. The half-maximal inhibitory concentration (IC50) values were determined to be 36.17 ± 0.21 μg/mL for the biosynthesized AgNPs and 72.15 ± 0.11 μg/mL for M. micrantha extract, confirming the substantial anticancer potential of the biogenic nanoparticles.

Breast cancer remains one of the most common malignancies affecting women worldwide. Despite the effectiveness of traditional chemotherapeutic agents such as 5-fluorouracil (5-FU), their lack of selectivity often results in damage to healthy tissues, leading to undesirable adverse effects. The aim of this study was to modify 5-FU with mannose containing 1,2,3-triazole compound to reduce its toxic effect, and to investigate the anticancer properties of the resulting 5-FU derivative (5-FUD-Man) in ER-positive MCF-7 breast cancer cells. Our results demonstrated that while 5-FU caused significant cytotoxicity in both cancerous and healthy cells, 5-FUD-Man showed selective cytotoxicity, with minimal effects on MCF-10A cells. Furthermore, immunofluorescence staining results indicated that 5-FUD-Man was more strongly activated apoptosis (Caspase-3, AIF), autophagy-mediated (LC3B), and stress-associated signaling pathways (ERK1/2) in MCF-7 cells compared to 5-FU. These findings suggest that the combined use of carbohydrate-based targeting via mannose and a bioactive triazole compound may enhance the selectivity and therapeutic efficacy of 5-FU-based treatments in breast cancer. Overall, 5-FUD-Man appears to be a promising candidate for further development as a more targeted and potentially safer therapeutic strategy.