Anti-cancer Agents In Medicinal Chemistry[JOURNAL]
Sun
200 papers
Oxygen Free Radicals and Cancer: Protective Role of Endogenous Antioxidants and Natural Compounds.
Irfan Z, Firdous SM, Giri S … +1 more , Hashmi A
Anticancer Agents Med Chem · 2026 Mar · PMID 41940428 · Publisher ↗
INTRODUCTION: Reactive oxygen species (ROS) are highly reactive oxygen-derived molecules that function as both potent inducers of cellular damage and essential signalling mediators. In a physiological setting, normal ROS...
INTRODUCTION: Reactive oxygen species (ROS) are highly reactive oxygen-derived molecules that function as both potent inducers of cellular damage and essential signalling mediators. In a physiological setting, normal ROS levels control vital functions like immune responses, cell division, and proliferation. However, oxidative stress, which is a major factor in the onset and spread of cancer, is caused by a disturbance in redox equilibrium. METHODS: The published literature on ROS, antioxidant defense mechanisms, redox-sensitive signalling pathways, and the anticancer potential of natural substances was summarised and critically assessed in this review. A systematic analysis of peer-reviewed research on molecular mechanisms, signalling cascades, and therapeutic implications was conducted. RESULTS: DNA damage, lipid peroxidation, and protein oxidation are caused by excessive ROS production or impaired antioxidant defenses, which encourage genomic instability and oncogenic transformation. Increased ROS levels impact apoptosis, proliferation, and tumour growth by activating several redox-sensitive pathways such as NF-κB, PI3K/Akt, and MAPK. Both enzymatic and non-enzymatic antioxidants shield cells from oxidative damage, but they can also act as pro-oxidants in certain situations. By altering reactive oxygen levels, suppressing oncogenic signalling, and promoting apoptosis, natural compounds like curcumin, resveratrol, lycopene, and marine-derived metabolites show promising anticancer activity. DISCUSSION: The intricacy of redox control in cancer is highlighted by the dualistic involvement of ROS as tumour promoters and suppressors. Opportunities for redox-based therapeutic interventions are presented by cancer cells, related oxidative stress, and increased reliance on antioxidant systems. CONCLUSION: A precise understanding of ROS-driven mechanisms can help design targeted redox-based strategies for effective cancer prevention and treatment.
A Preliminary Study on Photodynamic Therapy for Central Tracheobronchial Malignant Tumours.
Gong B, Zhang Y, Wang T … +3 more , Zhang Q, Shen Y, Li W
Anticancer Agents Med Chem · 2026 Mar · PMID 41940427 · Publisher ↗
INTRODUCTION: Photodynamic therapy (PDT) holds considerable potential in inoperable central tracheobronchial malignant tumours. However, evidence is scarce from Chinese populations. This preliminary study was conducted t...
INTRODUCTION: Photodynamic therapy (PDT) holds considerable potential in inoperable central tracheobronchial malignant tumours. However, evidence is scarce from Chinese populations. This preliminary study was conducted to monitor the therapeutic efficacy and assess the safety of PDT for central tracheobronchial malignant tumours in a Chinese population. METHODS: This study involved nine patients with central tracheobronchial malignant tumours who underwent PDT. The primary endpoints of the study were clinical efficacy and safety, while secondary endpoints included the one-year overall survival (OS), two-year OS, and recurrence-free survival (RFS). RESULTS: Nine patients with a follow-up period exceeding two years, six patients exhibited sustained clinical stability for one year. After PDT, there was a significant improvement in both the clinical symptoms and the quality of life of the patients (t = 5.57, P<0.0001). The one-year OS reached 88.9%, while the two-year OS was 77.8%. Among the included patients, two patients with adenoid cystic carcinoma had not yet reached the average RFS, with a mean RFS of 15.9±10.5 months (ranging from 2.1 to 35.0 months). Adverse effects were limited, with two patients experiencing grade 1 photosensitivity reactions, one patient developing localized bronchial scarring. Importantly, no serious treatment-related complications were observed. DISCUSSION: This study demonstrates that PDT is associated with a favorable safety profile and significant therapeutic benefits, particularly when combined with multimodal comprehensive treatment strategies. While the small sample size and single-center design limit the generalizability of our findings, the data presented here provide important insights into the application of PDT for central airway malignancies in China. Future research should aim to include a larger, more diverse patient population to further validate the efficacy of PDT and explore its potential as a new treatment option for patients. CONCLUSIONS: This preliminary study establishes that PDT represents a viable and effective approach for the management of central tracheobronchial malignant tumours. PDT yields favourable survival outcomes while being associated with mild and well-tolerated complications. Overall, this study highlights the significant clinical value of PDT.
Amlodipine Targeting SPINK1 Attenuates Lung Cancer Cell Growth and Proliferation Through Glycolytic Metabolism.
Yue G, Yue L, Chen Y … +8 more , Yang H, Chen X, Zhao Y, Xing S, Shen G, Zhou L, Zhang Y, Bai Y
Anticancer Agents Med Chem · 2026 Mar · PMID 41940426 · Publisher ↗
INTRODUCTION: A trypsin inhibitor, the serine peptidase inhibitor, Kazal type 1 (SPINK1), a secreted protein, has been identified in recent years as contributing to the advancement of specific cancer types. Lung cancer i...
INTRODUCTION: A trypsin inhibitor, the serine peptidase inhibitor, Kazal type 1 (SPINK1), a secreted protein, has been identified in recent years as contributing to the advancement of specific cancer types. Lung cancer is a common class of malignant tumors. However, the role of SPINK1 in lung cancer is unknown. This study aimed to investigate the profound mechanism of SPINK1 in lung cancer. METHODS: In this study, we used bioinformatics methods to select lung cancer samples for single-cell sequencing analysis, including CNV analysis, GSVA analysis, mimetic timing analysis, and intercellular communication, to identify potential molecular targets and pathways. We selected A549 cells and SPC-A1 cells to evaluate the role of SPINK1 in tumorigenesis in vitro. RESULTS: The study indicated that SPINK1 expression was significantly elevated in tumor tissue compared with normal tissue, and higher levels correlated with poorer patient prognosis. Moreover, when SPINK1 was overexpressed, both BEAS-2B and SPC-A1 cells formed dense cell clusters, and SPINK1 overexpression significantly promoted the formation of cell clones. DISCUSSION: Amlodipine (AML) treatment decreases mRNA and protein expression of CDK1, BCL-2, CyclinE1, and CCND1 in A549 and SPC-A1 cells by targeting SPINK1, which regulates glycolytic metabolism. CONCLUSION: The present study suggests that SPINK1 may modulate glycolytic metabolism in lung cancer cells, inhibiting their growth and proliferation, and potentially providing therapeutic insights.
Chitosan-Gold Nanogel Loaded with Doxorubicin: An Enhanced Delivery System for NSCLC Lung Cancer.
Aminirad E, Esfahlan TH, Rajabi A … +4 more , Fathi M, Saber A, Feizi MAH, Safaralizadeh R
Anticancer Agents Med Chem · 2026 Mar · PMID 41940425 · Publisher ↗
INTRODUCTION: Lung Cancer (LC) is the leading cause of cancer deaths globally. Long non-coding RNAs (lncRNAs) have emerged as important regulators in lung cancer, playing key roles in tumor development and metastasis. Re...
INTRODUCTION: Lung Cancer (LC) is the leading cause of cancer deaths globally. Long non-coding RNAs (lncRNAs) have emerged as important regulators in lung cancer, playing key roles in tumor development and metastasis. Recent advances in nanoparticle-based drug delivery systems and lncRNA research offer promising strategies to enhance treatment efficacy and reduce adverse effects. METHODS: CS/AuNPs were synthesized via chloroauric acid reduction in chitosan solution, and DOX was incorporated using TPP crosslinking to form CS/AuNP-DOX. The nanoparticles were characterized by FT-IR spectroscopy, particle size, and zeta potential analysis. The in vitro effects of CS/AuNP-DOX on cytotoxicity (IC50), apoptosis, cell cycle, and lncRNA expression were evaluated. RESULTS: CS/AuNP-DOX demonstrated enhanced anticancer activity compared to free DOX, with reduced IC₂⁽ (1.36 μM vs. 1.9 μM), increased apoptosis (57% vs. 37%), and greater G2/M phase cell cycle arrest. Importantly, CS/AuNP-DOX induced only limited apoptotic and cell-cycle effects in normal cells (HFFF2). Additionally, treatment with CS/AuNP-DOX significantly downregulated the expression of HIF1A-AS1 and DLGAP1-AS2. DISCUSSION: The enhanced therapeutic efficacy and reduced toxicity observed in this study suggest that CS/AuNP-DOX may overcome limitations of conventional chemotherapy by improving drug bioavailability. CONCLUSIONS: These findings highlight the potential of integrating nanoparticle-based drug delivery with lncRNA-targeted therapies to improve lung cancer treatment. However, further in vivo studies are required to confirm these results.
Ginkgolide A Suppresses Osteosarcoma Proliferation and Activates the Apoptotic Pathway by Targeting the KAT2A-H3K18la Lactylation Axis.
Fu C, Wu J, Hou S … +9 more , Liu M, Wang S, Du Q, Yu H, Wang S, Feng F, Xu K, Wang C, Nisar MF
Anticancer Agents Med Chem · 2026 Mar · PMID 41940424 · Publisher ↗
INTRODUCTION: Osteosarcoma (OS) is a highly aggressive primary bone malignancy characterized by profound metabolic reprogramming and limited therapeutic options. Although histone lactylation has recently emerged as a met...
INTRODUCTION: Osteosarcoma (OS) is a highly aggressive primary bone malignancy characterized by profound metabolic reprogramming and limited therapeutic options. Although histone lactylation has recently emerged as a metabolic-epigenetic mechanism linking glycolysis to gene regulation, its functional relevance and therapeutic tractability in OS remain largely unexplored. Here, we identify the natural diterpene lactone Ginkgolide A (GA) as a potent suppressor of OS progression through targeted disruption of lactate-driven histone lactylation. METHODS: Human Osteosarcoma (OS) MG63 and U2OS cell lines were given GA to find cell viability loss, migration, and apoptosis, which were examined using CCK-8 assay, wound-healing assay, Annexin V/PI flow cytometry, TUNEL staining, qRT-PCR, and immunoblotting. Gas Chromatography Mass Spectrometry (GC-MS) metabolomics was employed to profile the metabolic changes induced by GA, with a focus on the glycolytic pathway. In-depth ligation patterns and regulatory mechanisms of histone were studied herein through sitespecific immunoblotting, Chromatin Immunoprecipitation (ChIP)-qPCR, immunofluorescence, and Molecular Docking (MD) tools. Later on, the antitumor potential of GA was further examined using a nude mouse xenograft model. RESULTS: GA significantly checked OS cell proliferation and migration by modulating apoptosis, with halfmaximal inhibitory concentrations of 10.83 μM (MG63 cells) and 12.88 μM (U2OS cells). GA boosts mitochondrial apoptosis, indicated by enhanced BAX and caspase-3/-9 levels while repressing the expression level of BCL-2. Integrated metabolomic profiling indicated a marked decline of intracellular lactate and acetate levels, which establishes a metabolic basis for downstream epigenetic remodeling by GA. GA showed a site-specific epigenetic regulation by targeted suppression of histone H3 lysine-18 lactylation (H3K18la) with no effect on non-target lactylation sites. GA may downregulate expression of lactyltransferase KAT2A, alter H3K18laassociated promoter occupancy of apoptosis-linked genes, and induce pro-apoptotic transcriptional activity. In the xenograft in vivo model, GA modulated apoptosis to significantly inhibit tumor growth and expression of Ki67. DISCUSSION: Findings reported in the present study confirmed that GA directly interacts with KAT2A, inhibits lactylation by disrupting the binding of KAT2A with H3K18, thereby regulating OS cell proliferation. CONCLUSION: GA markedly inhibits proliferation, migration, and induces apoptosis in OS cells primarily by regulating the glycolytic pathway, i.e., reduction in lactate levels, subsequent targeting of KAT2A, downregulation of H3K18 lactylation, and ultimate transcriptional regulation of apoptosis. It is hereby recognized that GA mediates metabolic inhibition by selective epigenetic reprogramming of the KAT2A-H3K18 lactylation axis. The current findings establish histone lactylation as a key mechanism in OS inhibition and highlight metabolicepigenetic cross-talk as a promising therapeutic regimen for aggressive bone malignancies.
MVs and MVs-Crocin as Novel Therapeutic Agents for Lung Cancer, Apoptosis, and Gene Regulation.
Keshavaerz H, Zand B, Nilchiani LS … +2 more , Halabian R, Heshmati F
Anticancer Agents Med Chem · 2026 Mar · PMID 41940423 · Publisher ↗
INTRODUCTION: Lung cancer is one of the most common malignancies worldwide. Stem cells and their secretions have recently attracted attention as potential therapeutic agents due to their anti-cancer properties. This stud...
INTRODUCTION: Lung cancer is one of the most common malignancies worldwide. Stem cells and their secretions have recently attracted attention as potential therapeutic agents due to their anti-cancer properties. This study investigated the effects of mesenchymal stem cell-derived microvesicles (MVs) and Crocinpreconditioned MVs (MVs-Crocin) on lung cancer cells (A549) compared with normal cells (HEK293). MATERIALS AND METHODS: Mesenchymal stem cells were preconditioned with Crocin, and microvesicles were subsequently isolated. The appropriate therapeutic concentrations of MVs and MVs-Crocin were determined using the MTT assay. A549 and HEK293 cells were treated with the optimized doses. Apoptosis was assessed by flow cytometry, and the expression of apoptotic genes was analyzed through real-time PCR. RESULTS: MTT assay results identified 40 μg/ml for MVs and 50 μg/ml for MVs-Crocin as optimal therapeutic concentrations. Treatment with MVs and MVs-Crocin significantly reduced the survival of A549 cells, while apoptosis assays and gene expression analysis confirmed enhanced apoptotic activity in treated cancer cells. DISCUSSION: Both MVs and MVs-Crocin demonstrated potent anti-cancer effects by reducing lung cancer cell survival and inducing apoptosis. Preconditioning with Crocin appeared to further strengthen the therapeutic efficacy of MVs. Importantly, these effects were more pronounced in cancer cells compared to normal cells, indicating selective anti-cancer potential. CONCLUSION: MVs and MVs-Crocin promote apoptosis in lung cancer cells and may serve as promising candidates for the development of novel therapeutic strategies against lung cancer.
Current Progress and Future Opportunities in Liquid Biopsy for Cancer Detection.
Yasaei M, Fazilat A, Khavanin A … +6 more , Yadegari F, Kamrani S, Majidzadeh K, Sheykhi-Sabzehpoush M, Valilo M, Farzaneh M
Anticancer Agents Med Chem · 2026 Apr · PMID 41935357 · Publisher ↗
INTRODUCTION: Cancer is a leading cause of death worldwide, with many cancers lacking effective early screening methods. Early diagnosis is critical for improving survival and quality of life, and for reducing the financ...
INTRODUCTION: Cancer is a leading cause of death worldwide, with many cancers lacking effective early screening methods. Early diagnosis is critical for improving survival and quality of life, and for reducing the financial burden of late-stage treatment. Liquid biopsy has emerged as a promising, minimally invasive diagnostic strategy. METHODS: This review provides a comprehensive analysis of the current state of liquid biopsy technologies for cancer detection. It evaluates the primary analytical techniques used to detect circulating tumor biomarkers, including Circulating Tumor Cells (CTCs), cell-free DNA (cfDNA), various non-coding RNAs (ncRNA), and extracellular vesicles. RESULTS: Liquid biopsies enable molecular characterization for diagnosis, treatment classification, and monitoring. However, the analysis reveals that a significant weakness of many current techniques is insufficient sensitivity for reliably detecting early-stage cancers, when treatment is most effective. DISCUSSION AND CONCLUSION: While liquid biopsy represents a revolutionary approach to oncology, technological hurdles remain. This review addresses these challenges and provides recommendations for advancing biomarker assay sensitivity and specificity. Overcoming these limitations is essential for translating liquid biopsy into effective, widespread clinical screening for early cancer detection.
Anticancer and Drug-Likeness Evaluation of Allylphenol-Based 15-LOX Inhibitors in Prostate Cancer: An In Vitro and Computational Study.
Khezri E, Sadeghian H, Gharaee ME … +4 more , Samei M, Rassouli FB, Sani FV, Mosaffa F
Anticancer Agents Med Chem · 2026 Apr · PMID 41935356 · Publisher ↗
BACKGROUND: Prostate cancer remains the second most common cancer among men around the world, with 1.4 million new cases annually. Treatment resistance and off-target toxicity require innovative therapeutic approaches. N...
BACKGROUND: Prostate cancer remains the second most common cancer among men around the world, with 1.4 million new cases annually. Treatment resistance and off-target toxicity require innovative therapeutic approaches. Natural compounds such as eugenol exhibit anticancer potential, but poor pharmacokinetic properties constrain clinical application. OBJECTIVE: This study evaluated the cytotoxic, apoptotic, and pharmacokinetic properties of three eugenolderived allyl phenol compounds (38, 42, 47), previously recognized as potent 15-lipoxygenase-1 (15-LOX-1) inhibitors, in prostate cancer models. METHODS: The cytotoxic activity was evaluated in PC-3 prostate cancer cells and Human Dermal Fibroblasts (HDF) using AlamarBlue assays, flow cytometry, and morphological analysis. Computational validation involved Density Functional Theory (DFT) calculations, molecular docking into 15-lipoxygenase-1 (15-LOX-1; PDB: 2P0M), and structural analysis. Pharmacokinetic and toxicity profiles were predicted in silico using SwissADME, pkCSM, and ProTox-III platforms. RESULTS: All three compounds were cytotoxic to PC-3 cells in a concentration-dependent way with some selectivity for normal cells. Apoptosis was confirmed by increased sub-G1 peak and morphological changes, while BAX or BCL-2 mRNA levels did not change. In silico studies (DFT and docking) showed that the compounds bound well to 15-LOX-1 (docking scores: -6.6 to -7.3 kcal/mol), with compound 42 having the strongest binding affinity. Structural analysis showed that the proteins were moderately flexible (B-factor: 47.45 ± 13.07 Ų), which supports stable ligand accommodation. Computational ADME/toxicity predictions suggested generally favorable pharmacokinetic profiles; however, compound 42 was poorly soluble, and compound 47 was identified as a P-gp substrate, indicating a potential efflux liability. DISCUSSION: The pro-apoptotic effects observed despite unaltered BAX and BCL-2 mRNA levels indicate that the apoptotic response is likely mediated through mechanisms other than transcriptional regulation of these genes, potentially by blocking 15-LOX-1. Computational modeling indicated that all three compounds can effectively bind to the 15-LOX-1 active site, and their binding affinities are in line with their experimental inhibitory potencies (IC: 0.80-0.88 μM). The integration of in vitro and in silico results confirms the therapeutic potential of these compounds and underscores the necessity for additional mechanistic studies and in vivo evaluation. CONCLUSION: These results highlight the anticancer properties of eugenol-derived allylphenol compounds. The compounds induce apoptosis by mechanisms independent of BAX/BCL-2 transcriptional modulation. Computational modeling suggests potential involvement of 15-LOX-1; nevertheless, direct mechanistic validation via caspase activity, ROS generation, or protein-level quantification of BAX/BCL-2 is necessary to verify the apoptotic pathway. The compounds suggest favorable pharmacokinetic profiles along with strong enzyme binding characteristics. Compound 38 exhibited the most balanced profile, characterized by high cytotoxicity, selectivity, and predicted ADME properties. Additional mechanistic investigations and in vivo validation are necessary to advance these candidates through preclinical development.
Sulfonamides as Aromatase Inhibitors: Nimesulide Analogues, N-cyclic- and Aryl-Sulfonamides.
Maccallini C, Ammazzalorso A, De Filippis B … +3 more , Fantacuzzi M, Giampietro L, Amoroso R
Anticancer Agents Med Chem · 2026 Mar · PMID 41930603 · Publisher ↗
Aromatase catalyzes the final and rate-limiting step in the biosynthesis of estrogens. Inhibitors of this key enzyme are used to treat hormone receptor-positive early, locally advanced, and metastatic breast cancers and...
Aromatase catalyzes the final and rate-limiting step in the biosynthesis of estrogens. Inhibitors of this key enzyme are used to treat hormone receptor-positive early, locally advanced, and metastatic breast cancers and are classified by structure into steroidal and nonsteroidal classes. Non-steroidal inhibitors, in particular, bind non-covalently to the heme moiety of aromatase and prevent the binding of the substrate androstenedione by saturating the binding site. Several aromatase inhibitors have been developed to date, most of which share a common pharmacophore: (i) one or two aromatic rings that contribute to hydrophobic interactions, (ii) a triazole or imidazole that coordinates with the heme iron of aromatase, and (iii) hydrophobic groups that help the molecule fit into the lipophilic binding pocket of aromatase. In recent years, several studies have focused on developing aromatase inhibitors containing a sulfonamide group, which can form significant interactions with aromatase due to its ability to participate in hydrogen bonding. This review aims to describe the most significant structure-activity relationships of nonsteroidal aromatase inhibitors containing a sulfonamide moiety, focusing on (i) biological results related to enzyme inhibition and (ii) interactions with active-site residues of aromatase identified through molecular modeling. Based on their core scaffold, the molecules are classified into (i) analogues of nimesulide, (ii) N-cyclic sulfonamides, and (iii) aryl-sulfonamides.
Oleuropein and Colorectal Cancer Chemoprevention: Recent Advances into Cellular and Molecular Mechanisms.
Leto G
Anticancer Agents Med Chem · 2026 Mar · PMID 41930602 · Publisher ↗
A growing number of epidemiological studies provide strong evidence regarding the significant association between Olive Oil (OO) consumption and reduced risk of colorectal cancer (CRC). The chemopreventive effects of OO...
A growing number of epidemiological studies provide strong evidence regarding the significant association between Olive Oil (OO) consumption and reduced risk of colorectal cancer (CRC). The chemopreventive effects of OO on CRC growth and progression appear likely to be related to the presence, among various components, of "minor bioactive compounds", such as flavonoids, phenolic acids, alcohols, lignans, and secoiridoids, as these molecules have been shown to be endowed with antioxidant, anti-inflammatory, immunomodulatory, and anticancer properties. In particular, Oleuropein (Ole), the major glycosylated secoiridoid found in olive leaves and fruits of the olive tree (Olea europea L.), has attracted growing interest as this molecule exhibits a remarkable anticancer activity. The antitumor activity of Ole appears to rely on targeting multiple signalling pathways underlying cancer cell growth and progression. These observations further indicate a possible therapeutic role of this molecule in the prevention and treatment of human tumors. On the basis of these observations, a growing number of preclinical in vitro and in vivo investigations have been undertaken to unravel the specific mechanisms underlying the antitumor activity of Ole and to assess its potential therapeutic effectiveness in the prevention and treatment of CRC. The results from these studies underpin the potential clinical role of Ole in the prevention and treatment of CRC and may pave the path for more effective and less toxic therapeutic approaches to the prevention and clinical treatment of this tumor and other human neoplasms. This review provides further insight into the molecular mechanisms through which Ole may counteract the growth and progression of CRC and examines the results from emerging studies that underpin the potential clinical role of this molecule in the prevention and treatment of this neoplastic disease.
Anthracycline Drugs: An Update on Chemistry, Structure-Activity Relationship, Mechanism of Action, Cardiotoxicity, Physicochemical and Pharmacokinetic Properties.
Pashaei Y, Kulabaş N, Şenkardeş S
Anticancer Agents Med Chem · 2026 Mar · PMID 41930601 · Publisher ↗
OBJECTIVE: This review aims to examine the literature on FDA-approved anthracyclines, focusing on their physicochemical and pharmacokinetic properties, and to analyze relevant studies for insights into chemistry, structu...
OBJECTIVE: This review aims to examine the literature on FDA-approved anthracyclines, focusing on their physicochemical and pharmacokinetic properties, and to analyze relevant studies for insights into chemistry, structure-activity relationships (SAR), mechanisms of action, and cardiotoxicity, to guide safer clinical use and future drug development. METHODS: A systematic literature search was conducted across PubMed, Scopus, Web of Science, ScienceDirect, and Google Scholar up to June 2025. Eligible articles included experimental, clinical, and review data on anthracyclines. RESULTS: Anthracyclines act primarily through DNA intercalation, topoisomerase II poisoning, generation of reactive oxygen species, and histone eviction. Key SAR determinants include the aglycone core (C-13, C- 14, and C-4 substituents) and the daunosamine sugar; metabolic conversion to C-13 secondary alcohols and disturbed iron handling are major drivers of chronic cardiotoxicity. Clinically, safe administration relies on cumulative dose limits and cardiac monitoring, while liposomal formulations are validated strategies to reduce toxicity without compromising antitumor efficacy. DISCUSSION: Integrating SAR, physicochemical, and pharmacokinetic insights provides a framework for rationally modifying scaffolds and optimizing delivery systems to expand the therapeutic window. Advances in understanding cardiotoxicity mechanisms support the development of cardioprotective agents, chemical modifications, and clinically validated strategies such as liposomal formulations, while emerging green nanomaterials, combined with nanocarrier-based co-encapsulation strategies, represent a promising, sustainable, and biocompatible approach. This review emphasizes clinically relevant dosing regimens, pharmacokinetic parameters, and cardiotoxicity thresholds, enabling consistent comparisons of FDA-approved anthracyclines. CONCLUSION: This review clarifies key determinants of anthracycline efficacy and toxicity and recommends actionable strategies, including SAR-guided analogues and validated delivery systems, to advance safer therapies.
Research Progress on Desmoid Tumors: New Perspectives from Molecular Mechanisms to Clinical Management.
Lyu G, Zhang Y, Li D
Anticancer Agents Med Chem · 2026 Mar · PMID 41930600 · Publisher ↗
Desmoid Tumors (DT) are rare fibromatoses that are locally invasive. These are described as being monoclonal, and they tend to recur. Their clinical features are also different, and the prognoses of these tumors are not...
Desmoid Tumors (DT) are rare fibromatoses that are locally invasive. These are described as being monoclonal, and they tend to recur. Their clinical features are also different, and the prognoses of these tumors are not predictable. The recent achievements made in molecular genetics and the encouragement of multidisciplinary treatment modes have made a tremendous contribution to the diagnosis, treatment strategies, and qualityof-life measures of patients with DT. This is a narrative review that summarizes clinical, molecular pathology, conventional, and new areas of treatment, prognosis, and the current research on quality of life assessment tools in DT. It specifically highlights the uses and opportunities of targeted therapies, such as the secretase inhibitor nirogacestat (DeFi trial, NCT03785964) and tyrosine kinase inhibitors, such as sorafenib, reporting substantial disease progression, and critically reviews the role of surgery, in the context of high recurrence rates of marginpositive or even margin-negative resection. The study indicates the significance of personalized treatment that varies treatment options with proper risk-benefit analysis of each patient. This review also explains that the heterogeneous nature of DT and the absence of a standard-of-care predetermine the necessity of such an individual approach. Future areas of research that would offer a more powerful scientific foundation for individual guidance are also mentioned.
Phytochemical Insights and Anticancer Potential of Solanum americanum Mill: A Multi-Omics Perspective.
Goswami PK, Antal S, Kumar R … +1 more , Dhiman P
Anticancer Agents Med Chem · 2026 Mar · PMID 41930599 · Publisher ↗
INTRODUCTION: Solanum americanum Mill is a medicinal plant, which is used in the traditional systems of medicine in Ayurveda, African, Pacific Islander, and Native American for treating fever, liver disorders, inflammati...
INTRODUCTION: Solanum americanum Mill is a medicinal plant, which is used in the traditional systems of medicine in Ayurveda, African, Pacific Islander, and Native American for treating fever, liver disorders, inflammation, infections, and cancer. Notwithstanding its widespread traditional use and claims, rigorous scientific investigation of its phytochemical constitution and biological activities, including its anticancer potential, is lacking and scattered. In this review, the authors investigate the phytochemical constituents, pharmacological activities, and anticancer mechanisms of S. americanum, particularly focusing on the role of cutting-edge analytical approaches and multi-omics strategies in clarifying its therapeutic activities. METHODS: A thorough literature review of scientific databases was conducted to gather information on the traditional use of the plant, bioactive compounds, and pharmacological studies. Mechanistic studies on apoptosis, oxidative stress, and cell cycle arrest were conducted. High throughput HPTLC, HPLC, LC-MS, GC-MS, and NMR, as well as the Fire-blanket approach of genomics-transcriptomics-proteomics, and the integration of metabolomics data were used to strengthen molecular insights. ` Results: The plant species harbours different phytoconstituents, including steroidal glycoalkaloids such as solamargine and solasonine, flavonoids such as quercetin and kaempferol, and phenolic acids such as chlorogenic acid, which exhibit antioxidant, anti-inflammatory, antimicrobial, and anticancer activities. The anticancer effects are achieved through apoptosis, ROS production, and the Blockade of PI3K/Akt/mTOR and NF-κB pathways. Omics-profiling shows alterations in gene/protein expression and pathways that support the selective cytotoxicity, as well as the potential therapeutic utility of targeting it in cancer cells. DISCUSSION: The results also reflect the multitargeting potential of S. americanum as a therapeutic agent by virtue of its capacity to modulate several signaling pathways associated with cancer. The integration of omics technologies not only facilitates our insight into the molecular mechanisms of UA but also has the potential to support biomarker identification and target-based drug design. Nevertheless, additional preclinical and clinical trials would be required to validate efficacy, bioavailability, and safety. The authors highlight that standardization, pharmacokinetic assessment, and formulation optimization are crucial steps for the successful binging of S. americanum from bench to bedside. CONCLUSION: Solanum americanum Mill. has significant potential as a multi-targeted, plant-derived therapeutic agent in oncology. It is complemented by contemporary omics approaches to provide accurate phytochemical characterization and mechanistic rectification, thereby advocating its progression in personalized medicine and drug discovery flows.
Prognostic Value of Lactate Metabolism-Related Gene Signatures in Cancer Cells.
Mosaddeghi-Heris R, Hejazian SS, Karimi H … +8 more , Sevari FG, Youshanlouei HR, Taha SR, Zadeh MS, Abbasi K, Naghibi AF, Bagheri K, Farzaneh M
Anticancer Agents Med Chem · 2026 Mar · PMID 41930598 · Publisher ↗
INTRODUCTION: Predicting prognosis in cancer is complex. While traditional staging methods are useful, they do not fully account for the unique biology of each tumor. There is a growing need for biomarkers that capture t...
INTRODUCTION: Predicting prognosis in cancer is complex. While traditional staging methods are useful, they do not fully account for the unique biology of each tumor. There is a growing need for biomarkers that capture this biological nuance, which is where molecular signatures like those involved in lactate metabolism (LMRGs) come into play. METHODS: We conducted a structured narrative review of existing studies to investigate the link between LMRGs and patient survival. Our analysis spanned a wide array of cancers, from common types like breast and lung cancer to rarer forms such as sarcomas and gliomas, employing relevant keywords associated with lactate metabolism, gene signatures, and cancer prognosis. RESULTS: Our synthesis of the data suggests a consistent trend: higher activity of lactate metabolism genes may be associated with more aggressive disease. Across many different cancers, this signature was reliably associated with worse outcomes for patients, including shorter survival times. DISCUSSION: These findings suggest that LMRGs could be a valuable tool for dividing patients into more precise risk groups, potentially leading to more personalized treatment plans. However, moving this from research to the clinic will require overcoming hurdles like standardizing tests and proving its value in clinical trials. CONCLUSION: In summary, lactate metabolism genes may hold promise as a broadly applicable warning sign for aggressive cancer. Tapping into this metabolic 'switch' could ultimately help doctors better predict outcomes and tailor treatments for their patients.
ATP5B Expression as a Prognostic Biomarker in Solid Tumors: A Systematic Review and Meta-Analysis.
Li S, Qiao L, Sun B … +1 more , Huang J
Anticancer Agents Med Chem · 2026 Mar · PMID 41926307 · Publisher ↗
INTRODUCTION/OBJECTIVE: Mitochondrial ATP synthase F1 subunit beta (ATP5B) is involved in the catalytic process of oxidative phosphorylation (OXPHOS). However, the prognostic value of ATP5B remains conflicting. Therefore...
INTRODUCTION/OBJECTIVE: Mitochondrial ATP synthase F1 subunit beta (ATP5B) is involved in the catalytic process of oxidative phosphorylation (OXPHOS). However, the prognostic value of ATP5B remains conflicting. Therefore, a systematic meta-analysis is needed to assess the prognostic value of ATP5B in solid tumors. METHODS: A search for articles in multiple databases, including PubMed, Web of Science, China National Knowledge Infrastructure (CNKI), and Wanfang Data, was carried out for records up to June 1st, 2025. The analysis of the association between ATP5B expression levels and overall survival (OS) was conducted by calculating pooled hazard ratios (HRs) and 95% confidence intervals (CIs). Heterogeneity was measured via the I² statistic and Cochran's Q test. Subgroup analyses were performed to determine heterogeneity in ethnicity, cancer type, treatment regimen, data extraction method, sample size, and test target. Sensitivity and publication bias analyses were also performed. RESULTS: This meta-analysis included 12 studies (15 cohorts) with 2,344 patients. The results showed that high ATP5B expression was significantly associated with poor OS (HR = 1.95, 95%CI: 1.29-2.94). In subgroup analyses, reduced heterogeneity between studies was observed in the melanoma subgroup (I² = 44%), in studies based on mRNA expression (I² = 0%), and in studies with large sample sizes (I² = 0%). No significant bias was detected in the publication bias analysis. DISCUSSION: This first meta-analysis confirms the potential of ATP5B as a prognostic biomarker in solid tumors. High ATP5B expression is associated with poor prognosis, supporting its role as a pan-cancer indicator. More high-quality studies with large samples and standardized detection protocols are needed to further clarify the prognostic value of ATP5B, so that it may become a widely used biomarker in clinical practice. CONCLUSION: High ATP5B expression may independently predict inferior survival outcomes in patients with solid tumors.
Natural Products for Overcoming EGFR-TKI Resistance in NSCLC: A Narrative Review.
Guo Z, Ma Y, Guo C … +5 more , Liu T, Yang Y, Zhu M, Cao F, Kang X
Anticancer Agents Med Chem · 2026 Mar · PMID 41920751 · Publisher ↗
INTRODUCTION: Epidermal growth factor receptor tyrosine kinase inhibitor (EGFR-TKI) has transformed the treatment of non-small cell lung cancer (NSCLC), yet acquired resistance remains a major challenge to its clinical e...
INTRODUCTION: Epidermal growth factor receptor tyrosine kinase inhibitor (EGFR-TKI) has transformed the treatment of non-small cell lung cancer (NSCLC), yet acquired resistance remains a major challenge to its clinical efficacy. This review summarizes current advances in overcoming EGFR-TKI resistance with natural products and further discusses the emerging role of targeted protein degradation (TPD) as a complementary strategy to enhance the selective and irreversible clearance of resistant proteins. METHODS: We conducted a comprehensive literature review using the PubMed database with the keywords "natural products", "drug resistance", "EGFR-TKI", "targeted protein degradation", and "non-small cell lung cancer". RESULTS: Cumulative evidence indicates that a variety of natural products can reverse or mitigate EGFR-TKI resistance in NSCLC via multitarget modulation. These compounds have been shown to influence EGFR mutations, inhibit aberrant signaling pathways such as Phosphatidylinositol 3-Kinase (PI3K)/ Protein kinase B (PI3K/AKT), block histologic and phenotypic transformation, and reduce drug efflux. Moreover, natural product- based TPD approaches have shown initial promise in their potential to degrade resistance-associated targets and may enhance TKI sensitivity, hinting at possible therapeutic advantages. DISCUSSION: The reviewed evidence collectively supports the versatility of natural products in counteracting EGFR-TKI resistance. Integration with TPD strategies appears synergistic and may help address the limitations of single-agent therapy. CONCLUSION: Natural products, particularly when combined with TPD approaches, represent a promising strategy for overcoming EGFR-TKI resistance in NSCLC and may contribute to the development of more effective targeted therapies.
Marine-Derived Anticancer Compounds and their Clinical Status.
Kumar D, Goyal K, Sharma PK
Anticancer Agents Med Chem · 2026 Mar · PMID 41879493 · Publisher ↗
INTRODUCTION: Marine ecosystems provide an abundant reservoir of structurally diverse natural compounds that exhibit distinctive pharmacological activities. In recent decades, many bioactive molecules isolated from marin...
INTRODUCTION: Marine ecosystems provide an abundant reservoir of structurally diverse natural compounds that exhibit distinctive pharmacological activities. In recent decades, many bioactive molecules isolated from marine sources have been recognized as promising anticancer candidates. These agents act through multiple mechanisms, such as suppressing tumor cell proliferation, triggering programmed cell death, and influencing the tumor microenvironment. This review aims to provide a highlight of recent advances (2020-2025) in the discovery, preclinical evaluation, and clinical development of marine-derived compounds for cancer therapy, with emphasis on their structural diversity, biological activity, and clinical trial status. METHODS: Relevant literature was systematically searched in PubMed, ScienceDirect, Google Scholar, Scopus, SpringerLink, and https://clinicaltrials.gov/. using keywords "marine natural products," "anticancer activity," "clinical trials," and "FDA-approved marine drugs." Only studies published between 2020 and 2025 were included, and data on cell line activity were extracted. RESULTS: Several promising marine-derived compounds, including alkaloids, peptides, polyketides, and depsipeptides, have shown potent anticancer activity in in-vivo cell line models such as renieramycin M, salinosporamide A, bryostatins, halichondrin B, etc., while many of these compounds have achieved FDA approval, such as trabectedin, eribulin, plitidepsin, and lurbinectedin. While many other marine compounds are currently in clinical trials, they are expected to demonstrate therapeutic effects. DISCUSSION: Marine-derived compounds show significant anticancer potential due to their novel chemical structure and diverse mechanisms of action. Recent research studies have highlighted the efficacy of targeting tumor growth and minimizing the risk of resistance. Future research needs to conduct more clinical trials to support the results and to enable large-scale production of marine-derived compounds. CONCLUSION: Marine sources offer a wide variety of compounds, and modifying them provides researchers with new opportunities for drug development. Many marine-derived compounds have already shown strong pharmacological effects, with some even proven in clinical use. New studies suggest that marine compounds could also play an important role in anticancer drug delivery systems, making them a promising option for future treatments.
Targeting XBP1 in Cancer: A Review of Therapeutic Approaches and Strategies.
Mousavi Salehi A, Khavanin A, Azizidoost S … +4 more , Cheraghzadeh M, Khombi Shooshtari M, Farzaneh M, Abouali Gale Dari M
Anticancer Agents Med Chem · 2026 Mar · PMID 41833029 · Publisher ↗
X-box binding protein 1 (XBP1) is an essential unfolded protein response (UPR) transcription factor that has important roles in cancer biology. Malignant XBP1 signaling promotes tumor survival, drug resistance, and immun...
X-box binding protein 1 (XBP1) is an essential unfolded protein response (UPR) transcription factor that has important roles in cancer biology. Malignant XBP1 signaling promotes tumor survival, drug resistance, and immune evasion and thus represents a potential therapeutic target and biomarker. A structured literature search was conducted using PubMed, Embase, Springer, Elsevier, ISI Web of Knowledge, and Google Scholar. The studies that had investigated the expression, role, and therapeutic targeting of XBP1 in various cancers were identified and critically assessed. XBP1 overexpression is associated with aggressive phenotypes, metastasis, and drug resistance to chemotherapy, radiotherapy, and endocrine therapy in many cancers, including breast, colorectal, lung, ovarian, liver, prostate, and hematopoietic cancers. Aside from intrinsic tumor activities, XBP1 also modulates the tumor microenvironment by suppressing dendritic cell function, promoting T-cell exhaustion, and reprogramming. Preclinical data support that inhibiting the IRE1α-XBP1 pathway restores treatment sensitivity and shows synergy with immunotherapy. XBP1 is a molecular interface for ER stress adaptation, oncogenic progression, and immune modulation. The fact that XBP1 is both a prognostic biomarker and a therapeutic target underscores the translational potential of XBP1-targeted therapy to improve the outcome of cancer.
Study on the Mechanism of Post-Chemotherapy Metastasis in Breast Cancer Based on Metabolomics and Development of TCM Metabolic Regulators.
Yu Z, Wang W, Tao J … +4 more , Qiu Y, Wang M, Qiu Z, Zhu W
Anticancer Agents Med Chem · 2026 Mar · PMID 41833028 · Publisher ↗
INTRODUCTION: Breast cancer (BC) is a leading global malignancy in women. Although central to treatment, chemotherapy may paradoxically promote metastasis. The role of metabolic changes in chemotherapy- induced metastasi...
INTRODUCTION: Breast cancer (BC) is a leading global malignancy in women. Although central to treatment, chemotherapy may paradoxically promote metastasis. The role of metabolic changes in chemotherapy- induced metastasis remains unclear. This study aims to investigate the association between metabolic alterations and BC metastasis after CMF (cyclophosphamide (CCP), methotrexate (MTX), and 5-fluorouracil (5-FU)) chemotherapy. METHODS: A murine BC model treated with CMF was used. Metabolomic profiling identified altered pathways. Metastasis was assessed via tumor growth, hematoxylin and eosin (H&E), and immunohistochemistry (IHC). Phospholipid metabolism was inhibited with idelalisib combined with CMF. Traditional Chinese medicine (TCM) components were screened. Epicatechin (EC) was identified as a modulator of phospholipid metabolism and tested in CMF. RESULTS: Metabolomic analysis revealed a marked upregulation of phospholipid metabolism in CMF-treated BC mice, which was linked to enhanced metastasis. Intervening with idelalisib in combination with CMF abolished these protumorigenic effects. Among the screened TCM components, EC was identified as a modulator of phospholipid metabolism. Similarly, the combination of EC and CMF maintained chemotherapy's antitumor efficacy while substantially reducing metastatic spread. DISCUSSION: Our findings reveal that CMF chemotherapy induces phospholipid metabolic reprogramming, which drives BC metastasis. Targeting this pathway-either through pharmacological inhibitors (idelalisib) or natural compounds (EC)-can mitigate chemotherapy-induced metastasis without compromising tumor suppression. This suggests that metabolic modulation could be a viable strategy to enhance chemotherapy efficacy. CONCLUSION: Upregulated phospholipid metabolism is a critical mechanism behind chemotherapy-induced BC metastasis. Combining CMF with phospholipid-targeting agents (idelalisib or EC) offers a promising therapeutic approach to optimize chemotherapy outcomes. These results provide a theoretical foundation for developing novel combination therapies in BC treatment.
Medicinal Chemistry of Natural Anti-Skin Cancer Agents: An Evidence-Based Literature Review.
Al-Hasan M, Al Lawati A, Al Shuhaibi M … +6 more , Al Subeihi J, Al Hinai T, Al Badi Q, Al Lawati H, Sirasanagandla SR, Das S
Anticancer Agents Med Chem · 2026 Mar · PMID 41833027 · Publisher ↗
Globally, the incidence and prevalence of skin cancer have increased. Skin cancers involve an abnormal growth of cells. Skin cancers are classified into melanoma and nonmelanoma skin cancer (NMSC), and NMSC is further cl...
Globally, the incidence and prevalence of skin cancer have increased. Skin cancers involve an abnormal growth of cells. Skin cancers are classified into melanoma and nonmelanoma skin cancer (NMSC), and NMSC is further classified as squamous cell carcinoma (SCC) and basal cell carcinoma (BCC). In the present narrative review, we searched databases, such as PubMed, Scopus, and Google Scholar, to retrieve the relevant articles. The ideal selection of therapeutic options depends on the anatomical location, genetic composition, different tumor stages, the individual's age, and general health conditions. Various chemotherapeutic options are available for effective treatment, but there are various side effects of the drugs. Natural products (NPs) may be used as supplements. NPs can potentiate apoptosis, decrease cell growth, and prevent metastasis. They are also safe and effective. The present review summarizes the use of natural products, such as Aloe vera, eggplant, frankincense, milk thistle, turmeric, black raspberry, mistletoe, burdock root, Dong Quai, black salve, astragalus, Solanum sodomaeum, Calendula officinalis, Melaleuca alternifolia, Hypericum perforatum, Withania somnifera, Polypodium leucotomos, Rosmarinus officinalis, Alpinia galangal, hypericin, tea, coffee, genistein, grape seed, and silymarin. Larger clinical trials are needed to explore the safety profile of various natural products that have proven effective against skin cancer.
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