Cancer remains a major cause of global morbidity and mortality, with rising inci-dence and limited effectiveness of conventional therapies due to systemic toxicity, adverse effects, and multidrug resistance. These limitations underscore the need for safer, targeted, and biologically effective therapeutic alternatives. Phytochemicals, naturally occurring compounds such as flavonoids, alkaloids, terpenoids, and polyphenols, have garnered consider-able attention due to their broad-spectrum anticancer activities and favorable safety profiles. This review assesses the therapeutic potential of phytochemicals in cancer prevention and treatment, focusing on their molecular mechanisms, pharmacological relevance, and translational applications. A comprehensive literature survey of peer-reviewed articles, clinical studies, and database reports (2015-2025) was conducted using PubMed, Scopus, Science Direct, and Web of Science with search terms including "phytochemicals," "plant-derived compound", "cancer", "tumor", "anticancer activity," "molecular mechanisms," "chemopre-vention," "combination therapy," and "chemotherapy" with Boolean operators. Phytochem-icals demonstrated significant anticancer effects by inhibiting cell proliferation, inducing apoptosis, suppressing angiogenesis, and modulating key oncogenic pathways, such as PI3K/Akt/mTOR, MAPK/ERK, and NF-κB. Clinically approved phytochemical-based drugs, including paclitaxel and vinblastine, validate their therapeutic relevance, while compounds such as curcumin and resveratrol show encouraging outcomes in ongoing studies. Synergistic interactions with conventional chemotherapeutics further enhance their therapeutic potential. Overall, phytochemicals exert multi-targeted actions regulating oxidative stress, inflammation, and cell survival pathways, offering advantages of reduced toxicity and enhanced efficacy. However, challenges such as poor solubility and low bioavailability limit their clinical translation. Continued efforts toward advanced formulations and robust clinical validation are essential to advance their integration into modern cancer therapeutics.

The Non-Small Cell Lung Cancer (NSCLC) with rare genomic alterations poses a significant clinical challenge due to a lack of established therapeutic guidelines. We report the application of a precision medicine strategy integrating genomic profiling with in silico molecular docking to guide therapy for two patients harboring such rare mutations. Genomic analysis identified a rare EGFR exon 18/20 insertion in one patient and a resistant ALK C1156Y mutation in another. Selection of the appropriate drug was carried out using molecular docking simulations, which predicted high binding affinity of the irreversible EGFR inhibitor afatinib for the unique EGFR insertion and of the ALK inhibitor alectinib for the C1156Y-mutated kinase. We observed that the computationally-informed choices of afatinib and alectinib subsequently led to notable clinical and radiological improvements in the respective patients. The association between the docking predictions and clinical outcomes corroborates the utility of computational modeling for tailoring therapies, although the structural models provide mechanistic insight into drug efficacy against these rare mutations. The present integrated approach emphasizes the value of merging in silico methods into clinical decision-making to overcome the therapeutic uncertainty of uncommon oncogenic driver alterations.

mRNA sequencing analysis suggested that ubiquinone oxidoreductase subunit A10 (NDUFA10) may function as a key downstream effector of circRAPGEF5 in lung adenocarcinoma (LUAD) progression; however, the underlying mechanism remains unclear. This study aimed to explore the expression and clinical significance of NDUFA10 in LUAD cells and its role in cell proliferation and metastasis. Variations in NDUFA10 mRNA and protein expression between LUAD and adjacent normal tissues were assessed using the Cancer Genome Atlas Program (TCGA) and Tumor Immune Estimation Resource (TIMER) databases. These findings were subsequently validated in LUAD cell lines via Reverse Transcription Quantitative PCR (RT-qPCR). Further analyses included clinical correlation, Receiver Operating Characteristic (ROC), survival analysis, and Gene Set Enrichment Analysis (GSEA) of NDUFA10. The functional role of NDUFA10 was investigated in vitro at the cellular level. NDUFA10 mRNA expression was significantly upregulated in pan-cancer analyses and specifically in LUAD. Its expression levels correlated with clinical parameters, including metastasis (M stage) and patient gender. Elevated NDUFA10 expression demonstrated a negative correlation with overall survival (OS) and first progression (FP), and was associated with the best efficacy of anti-PD-1/PD-L1 antibody therapies. GSEA indicated significant enrichment of NDUFA10-related genes in pathways involving WNT and Notch signaling, as well as the TGFβ pathway regulating the epithelial-mesenchymal transition (EMT). In vitro, knockdown of NDUFA10 significantly suppressed LUAD cell proliferation, colony formation, migration, and invasion compared to control cells. This study focuses on the role of NDUFA10 in lung adenocarcinoma (LUAD). Through database screening and experimental verification, it was found that NDUFA10 is upregulated in LUAD. Its high expression is associated with advanced N stage (N2/N3), high pathological stage (III/IV), poor therapeutic effect and advanced age, suggesting its potential as a biomarker for poor diagnosis and prognosis. Further analysis indicates that NDUFA10 is associated with immune infiltration and involves pathways such as neuroactive ligand-receptor interaction and chemokine signaling. In vitro experiments have confirmed that knocking down NDUFA10 can inhibit the proliferation and metastasis of lung adenocarcinoma cells. This study provides a preliminary basis for the function and mechanism of NDUFA10 in LUAD. In the future, we will further explore how it affects tumor progression through the WNT/Notch/TGFβ pathway or ROS/ energy metabolism. Silencing NDUFA10 suppresses LUAD cell proliferation, migration, and invasion. The study suggested that circRAPGEF5 regulated NDUFA10 to facilitate the progression of LUAD.

Lenvatinib is the first-line drug used in the systemic treatment of advanced hepatocellular carcinoma (HCC),although its therapeutic efficacy is limited by emerging resistance mechanisms. Our study aims to investigate the molecular pathways underlying lenvatinib resistance in HCC to inform circumvention strategies for therapeutic resistance. Our findings demonstrated that solute carrier family 25 member 27 (SLC25A27) is upregulated in lenvatinib-resistant (Lenva-R) HCC cells by RNA sequencing (RNA-seq). Similarly, SLC25A27 expression is higher in Lenva-R than lenvatinib-sensitive (Lenva-S) HCC cells and tissues via Quantitative real-time PCR (qRT-PCR), western blot, and immunohistochemistry (IHC) in vitro and vivo. Cell Counting Kit-8 (CCK-8) assay was performed to determine cell viability. Colony formation assay was performed to determine cell proliferation capacity. DCFH-DA staining was used to detect the levels of intracellular reactive oxygen species (ROS). Observation of mitochondrial morphology by using transmission electron microscopy (TEM). The corresponding assay kits were used to analyze the levels of malondialdehyde (MDA), glutathione (GSH)/ oxidized glutathione disulfide (GSSG) ratio, and mitochondrial membrane potential (MMP). Gain- and loss-of-function experiments demonstrated that SLC25A27 promotes survival, proliferation and lenvatinib resistance in vitro. Mechanistic studies showed that SLC25A27 inhibits ferroptosis pathway via activating solute carrier family 7 member A11 (SLC7A11)/glutathione peroxidase 4 (GPX4). Dual-luciferase reporter experiments confirmed signal transducer and activator of transcription 3 (STAT3) significantly enhances SLC25A27 transcription. Moreover, artesunate promotes ferroptosis by inhibiting the STAT3/SLC25A27/ SLC7A11/GPX4 axis in vivo and in vitro. Overall, our study confirmed the combination of artesunate and lenvatinib significantly enhances the anti-HCC effect of lenvatinib, which promising therapeutic strategy to circumvent resistance in HCC.

Quinoline derivatives, often incorporating other heterocyclic structures, have shown a wide range of therapeutic potential, especially in the treatment of cancer. These compounds have demonstrated significant anticancer activity against various cell lines, including HeLa (human cervical cancer) and MDA-MB-435 (melanoma), exhibiting strong inhibitory effects. In this study, arylhydrazonopyrazole derivatives (3a-c) were employed in a series of multicomponent reactions to synthesize 3,5,6,7,8,9-hexahydropyrazolo[1,5-a]quinoline and pyran derivatives. Pyrazolo[1,5-a]quinoline derivatives, due to their structural properties, are considered valuable scaffolds for the development of novel drugs targeting similar biological pathways, with the potential for improved therapeutic efficacy. This study aimed to demonstrate the use of simple arylhydrazonopyrazole derivatives in multicomponent reactions with cyclic ketones and aromatic aldehydes. The resulting compounds were then assessed for their cytotoxic and antiproliferative activities. Following these reactions, further heterocyclization processes were conducted, incorporating the quinoline moiety into the final structures. These findings underscore the potential of pyrazolo[ 1,5-a]quinoline derivatives as promising candidates for drug discovery, offering new avenues for targeting diseases with related molecular mechanisms. The key starting compound in this study was 3,5-dimethyl-4-(2-phenylhydrazono)-4Hpyrazole, which has been utilized in numerous heterocyclization reactions. These reactions, involving various reagents, such as cyclic ketones and diketones in the presence of aromatic aldehydes, led to the formation of fused tetracyclic compounds. Arylhydrazonopyrazole derivatives (5a-c) were employed in multicomponent reactions to synthesize 3,5,6,7,8,9-hexahydropyrazolo[1,5- a]quinoline and pyran derivatives. The reactions were carried out using both conventional catalysts and ionic liquid-immobilized catalysts. Notably, the use of ionic liquid-immobilized catalysts resulted in higher yields of the desired compounds. In this study, new compounds were synthesized, characterized, and evaluated for their cytotoxicity against six cancer cell lines: A549, HT-29, MKN-45, U87MG, SMMC-7721, and H460. Additionally, the cytotoxic effects of the synthesized compounds were assessed against hepatocellular carcinoma (HepG2) and cervical carcinoma (HeLa) cell lines. Morphological studies of selected compounds were also conducted to further understand their effects on the cancer cells. Moreover, the cytotoxicity of the selected compounds was tested against seventeen different cancer cell lines, categorized by disease type. Morphological analyses of these selected compounds were also performed to gain deeper insights into their potential as anticancer agents. The inhibition assays of the tested compounds demonstrated significant activity against c-Met enzymatic activity, with IC50 values ranging from 0.25 to 10.30 nM. Additionally, potent inhibition was observed in the prostate PC-3 cell line, with IC50 values ranging from 0.19 to 8.62 μM. These promising results highlight the potential of these compounds and encourage further research to explore their therapeutic applications in the future.

Cancer stands as one of the leading causes of death worldwide, and lung cancer represents its most aggressive and persistent form. Traditional strategies for addressing lung cancer involve various medical therapies such as radiotherapy, chemotherapy, and surgical excision. Despite their prevalence, these conventional methods lack precision and inadvertently cause collateral damage to neighbouring healthy cells. Recently, nanotechnology has emerged as a potential strategy for the treatment and management of lung carcinomas, bringing about a transformative shift in existing approaches. The primary focus of this shift is on minimizing harmful effects and improving the bioavailability of chemotherapy drugs specifically targeted at tumour cells. Currently, transferosome nanocarrier systems are widely employed to overcome the obstacles presented by lung cancer. The utilisation of transferosomeloaded therapeutic medication administration technologies holds tremendous potential in regulating tumour cell growth and treating lung cancer. The purpose of this study is to provide an overview and analysis of current advancements in transferosome-based drug delivery systems, employing inhalational nanoparticle strategies for precise drug targeting in lung cancer management.

Colorectal adenocarcinoma (COAD) is a prevalent and lethal form of cancer. Understanding the molecular mechanisms underlying COAD progression is crucial for developing effective diagnostic and therapeutic strategies. This study aims to explore wound healing-related genes in COAD and their potential roles in tumorigenesis and prognosis using in silico and in vitro methodology. A set of 70 genes associated with the "wound healing" term ere extracted from the Gene Ontology (GO) database (GO:0042060) and a protein-protein interaction (PPI) network was constructed using the STRING database. The PPI network was analyzed with the Cyto- Hubba plugin in Cytoscape, identifying four major hub genes: MMP2, FN1, NF1, and PTK7. We then analyzed the expression of these hub genes across 16 COAD cell lines and nine normal colon cell lines using RT-qPCR, finding significant overexpression in COAD cell lines. ROC curve analysis confirmed the diagnostic potential of these genes, with MMP2, FN1, and NF1 showing high AUC values. Expression validation using the TCGA COAD cohort, OncoDB, and HPA databases corroborated these findings, highlighting the overexpression and high protein levels of these genes in COAD. Promoter methylation analysis indicated lower methylation levels in COAD samples, suggesting dysregulation through epigenetic mechanisms. Genetic alteration analysis via cBioPortal revealed a spectrum of mutations, with FN1 being the most frequently mutated. Prognostic analysis using a KM plotter showed that high expression of the hub genes is associated with poorer overall survival (OS) and disease-free survival (DFS). Functional state correlations via CancerSEA suggested that these genes promote cell cycle, proliferation, metastasis, and stemness in COAD. Expression analysis in immune cells and drug sensitivity analyses highlighted the roles of MMP2, FN1, and NF1 in macrophages and drug resistance. A miRNA-mRNA network constructed using miRNet identified hsa-miR-200a-3p as a central regulator. Finally, functional assays in HCT116 cells demonstrated that knockdown of MMP2 and FN1 reduced proliferation, colony formation, and wound healing, suggesting these genes as potential therapeutic targets in COAD. In conclusion, our study identifies MMP2, FN1, NF1, and PTK7 as key wound healing-related hub genes in COAD.

Gastrointestinal (GI) cancers represent some of the most common and lethal malignancies globally, underscoring the urgent need for improved diagnostic strategies. Traditional diagnostic methods, while effective to some degree, are often invasive and unsuitable for regular screenings. This review article explores integrating machine learning (ML) with liquid biopsy techniques as a revolutionary approach to enhance the detection and monitoring of GI cancers. Liquid biopsies offer a non-invasive alternative for cancer detection through the analysis of circulating tumor DNA (ctDNA) and other biomarkers, which when combined with ML, can significantly improve diagnostic accuracy and patient outcomes. We conducted a comprehensive review of recent advancements in liquid biopsy and ML, focusing on their synergistic potential in the early detection of GI cancers. The review addresses the application of next-generation sequencing and digital droplet PCR in enhancing the sensitivity and specificity of liquid biopsies. Machine learning algorithms have demonstrated remarkable ability in navigating complex datasets and identifying diagnostically significant patterns in ctDNA and other circulating biomarkers. Innovations such as machine learning-enhanced "fragmentomics" and tomographic phase imaging flow cytometry illustrate significant strides in non-invasive cancer diagnostics, offering enhanced detection capabilities with high accuracy. The integration of ML in liquid biopsy represents a transformative step in the early detection and personalized treatment of GI cancers. Future research should focus on overcoming current limitations, such as the heterogeneity of tumor-derived genetic materials and the standardization of liquid biopsy protocols, to fully realize the potential of this technology in clinical settings.

Liver cancer is a leading cause of cancer-related mortality, with about one million people losing their lives each year. The disease becomes even more dangerous when tumors cannot be removed through surgery. Globally, hepatocellular carcinoma (HCC) ranks third in terms of fatality rates among liver cancers. It is also the most frequent type of liver cancer. Due to the high mortality rate associated with this malignancy, it is a hotspot for researchers looking to improve treatment methods. Nanotechnology plays an important part in these attempts. Various types of nanoparticles (NPs) have been investigated for their ability to fight liver cancer. NPs are a vast class of materials. The article details the efforts made to include inorganic NPs, such as silver, gold, metal oxide, platinum, calcium, selenium, and other uncommon materials into drug delivery systems (DDS) for therapeutic, carrier, or imaging purposes. This review discusses the function of carbon-based NPs in DDS for the treatment of liver cancer, including polymeric, polysaccharide, lipid, and carbon dot NPs, all of which have been extensively researched for this purpose. The purpose of this review is to provide a concise overview of recent developments in the field of HCC based on current research and clinical diagnosis and treatment guidelines. Further goals include elucidating the current state of nanomaterials research, its limitations, and the potential for future advancements in the field, as well as the use of nanotechnology in the detection and treatment of HCC.

There is a relative lack of real-world data regarding the treatment of advanced squamous cell lung cancer (SqCLC) with anlotinib. This study aimed to investigate the clinical efficacy and safety of combining anlotinib with ICIs for the treatment of advanced SqCLC. Sixty patients with advanced SqCLC from December, 2017 to December, 2022, were retrospectively recruited in the final analysis. The overall survival (OS), adverse events (AEs), and short-term clinical effectiveness, including complete remission (CR), partial remission (PR), stable disease (SD), and progression disease (PD) of the study populations, were observed. Objective response rate (ORR) was defined as the combined percentage of CR and PR in all patients. Disease control rate (DCR) was defined as the combined percentage of CR, PR, and SD in all patients. Subgroups were classified based on age (<65 or ≥65), sex (female or male), and the eastern cooperative oncology group (ECOG) score (0-1 or 1-2). The median age of the study population was 65 years, and 41 (68.3%) of the participants were male. ORR was 21.67%, and DCR was 83.33%. The median PFS and OS were 7.5 and 19.5 months, respectively. Furthermore, the Kaplan-Meier curves demonstrated no significant difference (P >0.05) in PFS and OS between different age groups, sex, and ECOG scores. Bone marrow suppression was the most common AE, followed by immune pneumonia. The findings of this study confirmed the effectiveness and safety of anlotinib and ICIs for advanced SqCLC.