Current Cancer Drug Targets - Online First

The changing landscape of hepatocellular carcinoma detection and treatment is examined in this study, focusing on recent advancements in therapeutic methods across several stages. Early identification of hepatocellular cancer cells continues to pose a serious threat to human health and is of utmost significance. It is crucial to create a useful signature to diagnose hepatocellular carcinoma early.

Chemotherapy and immunotherapy are high-stage treatment options for hepatocytes cancer. These treatments can be coupled with nanotechnology to increase effectiveness and minimize adverse effects. Furthermore, immunotherapy and chemotherapy might be combined to increase therapeutic efficacy and overcome resistance. Artificial intelligence technologies have the potential to significantly enhance hepatocellular carcinoma diagnosis and management.

Numerous models performed as well as or better than experienced radiologists while indicating the ability to improve radiologists' accuracy, showing encouraging outcomes for applying Artificial Intelligence to hepatocellular carcinoma-related diagnostic tasks.

Treatment for hepatocellular carcinoma has changed dramatically, moving from traditional techniques to cutting-edge technologies. Precision in diagnosis, prognosis, and treatment has increased due to innovations like molecular diagnostics, tailored medicines, and nanotechnology. This change improves patient outcomes and presents encouraging avenues for future research and treatment of hepatocellular cancer.

Recent advances in imaging techniques, biomarkers, and personalized medicine approaches have improved diagnostic accuracy and treatment outcomes. The emergence of immunotherapy, targeted therapies, and combination regimens has expanded treatment options, offering new hope for patients with advanced disease.

Chronic myeloid leukemia (CML) is a myeloproliferative neoplasm characterized by the Philadelphia chromosome. Imatinib is considered the standard therapy for CML due to its targeted action against the BCR::ABL1 tyrosine kinase. However, resistance to imatinib often emerges, particularly in the advanced stages of CML. One factor associated with imatinib resistance is the overexpression of survivin (baculoviral IAP repeat-containing 5, BIRC5). YM155 is an innovative survivin inhibitor that suppresses survivin expression and triggers apoptosis. Combination therapy is a strategy used to enhance the effectiveness of cancer treatment and overcome resistance.

Our study explored the in vitro anticancer effects of YM155 as monotherapy and as a combination therapy with imatinib on imatinib-sensitive (K-562) and imatinib-resistant (K562-r) BCR::ABL1+ CML cell lines. Results: Survivin inhibition significantly reduced proliferation in both K-562 and K562-r cells. Combination therapy with YM155 and imatinib produced a synergistic effect. In K562-r cells (imatinib IC50 = 6 µM), the combination reduced the IC50 by 6.2-fold. In K-562 cells, the IC50 decreased by 16.3-fold. Both monotherapy and combination therapy markedly increased apoptosis, with combination therapy inducing significantly greater apoptosis. The combination also downregulated survivin and BCR::ABL1 tyrosine kinase expression and significantly reduced BCR::ABL1 mRNA levels.

YM155 enhances imatinib’s efficacy against both sensitive and resistant CML cells, overcoming resistance through synergistic inhibition of proliferation, increased apoptosis, and suppression of survivin and BCR::ABL1 expression. These results support further investigation of YM155-Imatinib combination therapy as a potential strategy for resistant CML.

Single-nucleotide polymorphisms (SNPs) are the major source of attraction for researchers as they significantly contribute to an individual's susceptibility to various diseases, as well as provide an insight into new diseases associated with a particular gene.

In this study, the data were retrieved from dbSNP till July 2021. DbSNP showed 103738 total SNPs in the human ERG gene, and out of them, 377 missense SNPs were selected for analysis. Twenty-six missense SNPs were found to be deleterious in all five SNP tools (SIFT, PolyPhen-2, Condel, PHD-SNP, SNPs&GO). These 26 SNPs were further checked for protein stability by iStable, I-Mutant, and MuPro. Collectively, 23 SNPs showed to decrease the protein stability. A comparison of the 3D structures of the wild type (predicted by trRosetta) and the mutated type was visualized using the Chimera tool.

Post-translational modifications identified T180, R302, S356, and Y452 as clinically significant sites, as they were involved in phosphorylation and methylation.

In this study, in silico SNP analysis was performed on the human ERG gene. ERG’s involvement in various types of diseases, as well as cancer, has made it a source of interest. It is an oncogene that is not only involved in the germ line differentiation of hemopoietic stem cells, but is also involved in cell proliferation, embryonic development, angiogenesis, inflammation, and apoptosis.

This study has provided detailed information on missense SNPs of the ERG gene. This work can be significant in the detection of genetic diseases and drug discovery, as it has shown involvement of the ERG gene.

Agonists of CD137, a co-stimulatory receptor expressed on activated lymphocytes, are under investigation, including their use in combination with immune checkpoint blockade. FS222 is a tetravalent bispecific antibody targeting both CD137 and programmed death-ligand 1 (PD-L1).

Fragment crystallizable regions with antigen-binding (Fcab™) domains with high avidity to CD137 were engineered and matured. A resulting Fcab was introduced into a human high-affinity PD-L1 monoclonal antibody, generating FS222. Valency variants of FS222 and its mouse surrogate (FS222m) were generated. Antibody properties were assessed in vitro, while antitumor efficacy and T-cell proliferation were evaluated in vivo.

FS222 could bind to two copies of each antigen concurrently (‘2+2’ binding). In T-cell activation assays, FS222 and a variant that is bivalent for CD137 and monovalent for PD-L1 activated T cells, whereas monovalent variants for CD137 did not. FS222 had no hook effect up to 300 nM and was superior to a heterodimeric ‘1+1’ CD137/PD-L1 bispecific antibody. In mixed lymphocyte reaction assays, FS222 and another bivalently linked antibody for PD-L1 were more potent than monovalent antibodies for PD-L1. In syngeneic mouse models, FS222m was associated with more peripheral T-cell proliferation and antitumor efficacy than all MC38 or most CT26.WT valency variants.

FS222 could potently target and activate high CD137-expressing tumor-infiltrating lymphocytes due to its high avidity for CD137. FS222 demonstrates activity when PD-L1 levels are limited, highlighting its potential activity in tumors insensitive to PD-1 blockade, and in situations requiring both PD-L1 and CD137 binding. This may have clinical relevance.

In this study, it was found that the ‘2+2’ structure of FS222 is superior to that of a ‘1+1’ CD137/PD-L1 antibody.

Enhanced angiogenesis and impaired vascular integrity facilitate cancer metastasis. There is accumulating evidence that cancer-derived exosomes take a functional role in these processes. In our previous study, we revealed that Golgi Membrane protein 1 (GOLM1) can promote metastasis of Hepatocellular Carcinoma (HCC), and miRNAs can modulate angiogenesis and vascular permeability in HCC. The objective is to reveal that GOLM1 can promote HCC progression in an exosomal miRNA-dependent way.

Comprehensive bioinformatics analysis and experiments were conducted to associate GOLM1 expression with angiogenesis in HCC. The effect of hepatoma cell-derived exosomes on Human Umbilical Vein Endothelial Cells (HUVEC) was tested. Exosomal miRNA expression was profiled and validated in GOLM1-knockdown HCC cells. Targets of miR-4449 and miR-3651 were predicted with online tools and validated in vitro. Correlation between miR-4449/miR-3651 and microvascular invasion or recurrence in HCC was assessed.

GOLM1 correlated with angiogenesis in HCC. HCC cell-derived exosomes can be transferred to endothelial cells, and GOLM1 can regulate exosome-induced angiogenesis and vascular permeability. In vitro experiments showed that GOLM1 knockdown reduced exosomal abundance of miR-4449 and miR-3651, which target KEAP1 and ZO-1, respectively. Elevated miR-4449 and miR-3651 expression were correlated with microvascular invasion and recurrence in HCC patients.

We demonstrated that GOLM1 can promote HCC progression independent of its role in modulating EGFR/RTK cell-surface recycling, indicating that patients with high GOLM1 expression may benefit more from anti-angiogenic drugs and highlighting the potential of targeting miR-4449 and miR-3651 to prevent angiogenesis and vascular leakiness in HCC. However, in vivo studies are further needed to validate the effect of miR-4449 and miR-3651 inhibitors in compromising angiogenesis and vascular permeability. Besides, a larger validation cohort is indispensable for establishing the correlation between miR-4449/miR-3651 expression and microvascular invasion and tumor recurrence in HCC.

Our findings suggest that, under the control of GOLM1, HCC cell-derived exosomal miR-4449 and miR-3651 increase angiogenesis and vascular permeability by targeting KEAP1 and ZO-1, highlighting the potential of exosomal miRNAs as promising therapeutic targets for HCC.

Thiazolidinedione (TZD) derivatives have gained significant attention as anti-cancer agents due to their diverse biological activities. The objective of the research was to investigate the potential of thiazolidine derivatives as inhibitors of Carbonic anhydrase XII, an isoform overexpressed in hypoxic tumor environments, to explore their application as anticancer agents targeting breast cancer.

The study employed a computational approach to evaluate thiazolidine derivatives as potential CA XII inhibitors. Acute toxicity and safety were evaluated using ProTox 3.0. Molecular docking was conducted to study interactions with the zinc-bound active site of CA XII. Molecular dynamics simulations were performed to validate the stability of the ligand-enzyme complex over 250 ns.

TZD derivatives demonstrated favorable physicochemical properties, high gastrointestinal absorption, and low toxicity risks. Molecular docking studies showed strong binding affinities with key hydrogen bonding and zinc coordination at the CA XII active site. Toxicity predictions indicated that most compounds had acceptable safety margins, reinforcing their potential as safe and effective CA XII inhibitors.

The findings suggest that thiazolidine scaffolds could serve as promising small-molecule inhibitors of CA XII by targeting its zinc-bound catalytic site, a mechanism consistent with previously reported CA inhibitor pharmacology.

The study demonstrates that TZD derivatives possess promising characteristics as CA XII inhibitors, with favorable physicochemical properties, strong binding affinity, stable ligand-protein interactions, and acceptable safety profiles. These findings highlight their potential for further in vitro and in vivo validation, supporting the continued exploration of thiazolidinedione scaffolds in the development of targeted anticancer therapies.

Epidermal Growth Factor Receptor (EGFR) is a well-established therapeutic target in cancer treatment. In this study, a novel N-phenylacetamide derivative of theobromine, designated as T-1-PA, was designed as a potential semisynthetic EGFR inhibitor.

The 3D structure, stability, and electronic reactivity of T-1-PA were determined using Density Functional Theory (DFT) analyses. Molecular docking, molecular dynamics (MD) simulations, Molecular Mechanics Generalized Born Surface Area (MM-GBSA), Protein–Ligand Interaction Profiler (PLIP), and Principal Component Analysis of Trajectories (PCAT) were employed to evaluate the binding affinity and inhibitory potential of T-1-PA against EGFR. Computational ADMET profiling was conducted to predict drug-likeness and safety. Subsequently, T-1-PA was semisynthesized and subjected to in vitro biological evaluation.

Computational analyses demonstrated a strong binding affinity of T-1-PA to EGFR. The compound exhibited favorable ADMET properties. In vitro assays revealed potent EGFR inhibition with an IC50 of 0.736 ± 0.005 μM. T-1-PA also inhibited the proliferation of HepG2 and MCF7 cancer cell lines with IC50 values of 0.88 ± 0.01 μM and 1.13 ± 0.01 μM, respectively. Flow cytometry analysis indicated induction of apoptosis and G1 phase cell cycle arrest in HepG2 cells. Additionally, T-1-PA significantly impaired HepG2 cell migration and wound-healing capacity.

The results validate the computational predictions and highlight the anticancer potential of T-1-PA through EGFR inhibition and antiproliferative activity. The compound's favorable pharmacokinetic and safety profiles further support its therapeutic promise.

T-1-PA is a promising semisynthetic compound with selective antiproliferative activity mediated via EGFR inhibition. These findings encourage further preclinical investigation of T-1-PA as a novel candidate for EGFR-targeted cancer therapy.

There is no consensus on the impact of young age (≤ 35 or 40) on breast cancer prognosis. In this study, a meta-analysis was carried out on the prognosis of breast cancer in young women.

We searched PubMed, Embase, Web of Science, Cochrane, and key cancer-related international conference proceedings, from their inception to 1st June, 2023, with an update on 15th July, 2023. Studies were included if they reported hazard ratios (HRs) with 95% confidence intervals (CIs) or presented Kaplan–Meier survival curves. The main outcomes were overall survival (OS), disease-free survival (DFS), breast cancer–specific survival (BCSS), local recurrence–free survival (LRFS), distant disease–free survival (DDFS), progression-free survival (PFS), and pathological complete response (pCR). This meta-analysis was registered in PROSPERO (CRD42023459282).

The meta-analysis, including 129 studies with approximately 1,065,000 patients, reported that young breast cancer (YBC) patients had worse OS (HR = 1.30; 95% CI: 1.17 - 1.43; I² = 93%; P < 0.01), DFS (HR = 1.58; 95% CI: 1.47 - 1.70; I² = 68%; P < 0.01), BCSS (HR = 1.28; 95% CI: 1·09 - 1.49; I² = 95%; P < 0.01), LRFS (HR = 2.05; 95% CI: 1.59 - 2.59; I² = 70%; P < 0.01), DDFS (HR = 1.44; 95% CI: 1.11 - 1.87; I² = 91%; P < 0.01), and PFS (HR = 1.54; 95% CI: 1.16 - 2·03; I² = 90%; P < 0.01) and a greater pCR rates than non-young breast cancer (NYBC) patients (odds ratio (OR) = 1.45; 95% CI: 1.16 - 1.82; I² = 87%; P < 0.01). Subgroup analysis demonstrated that, compared with NYBC patients, certain differences were found in the prognoses of YBC patients with different molecular subtypes, regions, and stages.

This meta-analysis confirmed that YBC patients have worse survival outcomes than NYBC patients, despite having higher pCR rates. Subgroup analyses demonstrated that outcomes varied by molecular subtype, region, and disease stage. These findings underscore the importance of early screening, enhanced patient education, and tailored treatment strategies for YBC patients.

Patients with YBC had worse OS, DFS, BCSS, LRFS, DDFS, PFS, and greater pCR rates than NYBC patients.

Esophageal squamous cell carcinoma (ESCC) stands as one of the deadliest cancers globally. Given the urgent clinical need for more precise and comprehensive therapeutic strategies, the phytocompound methylophiopogonanone A (MO-A) demonstrates the potential as a candidate for ESCC treatment. This study aimed to verify the therapeutic effect of MO-A against ESCC and unveil its underlying mechanism.

Three compound-protein interaction databases were utilized to predict the molecular targets of MO-A. Subsequently, potential therapeutic targets of ESCC were identified based on the GEO database. KEGG pathway and GO function enrichment analyses were then performed by using these two sets of targets, respectively. Through the integrative analysis of these two target sets, core targets of MO-A with therapeutic potential against ESCC were determined. Protein-protein interaction network analyses and molecular dockings were executed by using these targets. Two human-derived ESCC cell lines were enrolled for biological validation, including cell viability, colony formation, and cell cycle assays.

This study predicted 200 potential targets of MO-A and uncovered 138 key targets associated with the progression of ESCC. Enrichment analyses and PPI networks underscored the involvement of cell cycle-related genes in ESCC development. Four proteins were determined as core MO-A targets for ESCC treatment, including AURKA, AURKB, CDC25B, and TOP2A, which partake in the regulation of the cell cycle. Finally, the inhibitory effect of MO-A on ESCC cell proliferation was validated in vitro, primarily through inducing cell cycle arrest at the G2/M phase in ESCC cells.

These results revealed the anti-ESCC potential of MO-A, a plant-derived flavonoid, using integrated bioinformatics and biological experiments. While findings provide a mechanistic basis for the efficacy of MO-A, limitations include reliance on computational and in vitro models. Further studies should be conducted to evaluate the pharmacological properties and safety of MO-A across multiple models, alongside more comprehensive structure-activity relationship studies to inform drug optimization prior to clinical translation.

MO-A can impede ESCC growth by triggering cell cycle G2/M arrest, positioning it as a novel and promising phytocompound for ESCC therapy.

Breast cancer is the most common malignancy among women and the second leading cause of cancer-related deaths worldwide. Resveratrol, a polyphenolic stilbene derivative found in grapes, red wine, and other plants, possesses anti-cancer properties. Various studies have reported the potential of different nanomaterials to act as radiosensitizers against tumor cells. This study aimed to evaluate the antitumor and radiosensitizing effects of Resveratrol-Chitosan Nanoparticles (Res-Ch-NPs) in a DMBA-induced breast cancer mouse model.

Res-Ch-NPs were developed using the chitosan emulsification cross-linking technique. The particle size, entrapment efficiency, zeta potential, UV and FT-IR spectra, and drug release profile of Res-Ch-NPs were evaluated. The IC50 of Res-Ch-NPs, both individually and in combination with γ-irradiation, was calculated against the MCF-7 cell line using the MTT assay. The LD50 of Res-Ch-NPs was estimated, and 1/20 LD50 was used to assess the antitumor and radiosensitizing effects on breast cancer cell-bearing mice. The in vivo efficacy was evaluated in DMBA-induced breast cancer mice, examining tumor weight, volume, blood parameters (Hb%, RBCs, and WBCs), oxidative stress markers (MDA, GSH, SOD, and CAT), immune markers (INF-γ, TGF-β1, CD4, and CD8), and gene expression levels (p53, survivin, and STAT3). Additionally, histopathological examination of breast tissues was also carried out.

Res-Ch-NPs demonstrated high entrapment efficiency (82.46 ± 1.02), a polydispersity index (0.65 ± 0.03), and a particle size of 184.60 ± 17.36 nm with a zeta potential of -46.78 ± 0.57 mV. The UV spectra of resveratrol and Res-Ch-NPs showed strong absorption at 230 and 250 nm. FTIR analysis confirmed the chemical stability of resveratrol in Res-Ch-NPs. The maximum release of Res-Ch-NPs was recorded at 55.07% after 44 hours. The IC50 values of Res-Ch-NPs, both individually and combined with γ-irradiation, against MCF-7 cell viability were 38.26 and 24.8 ± 0.76 µg/mL, respectively. The LD50 of Res-Ch-NPs was found to be 2090 mg/kg body weight. Treatment of DMBA-injected mice with Res-Ch-NPs and γ-irradiation significantly reduced tumor weight and volume, improved blood Hb%, RBC, and WBC levels, as well as breast MDA, GSH, SOD, and CAT levels. Additionally, breast levels of INF-γ, TGF-β1, CD4, and CD8 were reduced in DMBA-injected mice treated with Res-Ch-NPs and γ-irradiation. Conversely, the combination treatment upregulated p53 in breast tissues and downregulated the expression of survivin and STAT3 genes.

The findings confirmed that Res-Ch-NPs enhanced radiosensitivity, facilitating tumor regression and immune restoration. The modulation of pro-inflammatory and antioxidant pathways suggests a dual therapeutic role, acting as both a radiation enhancer and a tumor-suppressing agent. However, further research is needed to optimize nanoparticle dosing, assess long-term safety, and facilitate clinical translation into human studies.

Resveratrol-grafted chitosan shows promise as a radiosensitizer for cancer treatment by enhancing the responsiveness of tumor cells to γ-irradiation through the modulation of proinflammatory and antioxidant markers. Understanding the interactions between p53, survivin, and STAT3 is crucial for developing effective breast cancer treatments. Targeting survivin and modulating STAT3 activity may offer potential for future anticancer therapies.

The incidence of brain metastases in patients diagnosed with advanced lung cancer is high, drawing significant attention to the risk factors associated with this progression.

A total of 252 advanced non-small cell lung cancer (NSCLC) patients with brain metastases were enrolled in this study between July 2018 and December 2023 from our hospital. Additionally, driver genes, including EGFR, ALK, ROS1, KRAS, and RET, were documented. Next-generation targeted sequencing of a 168-gene panel was conducted on all collected samples to explore the association between tumor genomic complexity and risk factors for NSCLC with brain metastases.

Among 252 lung cancer patients with brain metastases enrolled in this research, the most prevalent driver gene was EGFR, accounting for 39.29% (99 patients). Other driver gene mutations, such as KRAS, ALK, ROS1, and RET, accounted for 3.57%, 7.14%, 2.78%, and 0.4%, respectively. Kaplan-Meier analysis showed that patients with EGFR mutations had a more favorable overall survival (OS) compared to those without the mutation (P < 0.0001). Additionally, patients with ALK fusions had longer survival times compared to those with wild-type genes (P = 0.0021). In this study, patients were divided into two groups based on the presence or absence of copy-number alterations. Further survival analysis revealed that patients with copy-number alterations experienced significantly shorter overall survival compared to the control group (P = 0.041).

This study underscores the crucial role of driver mutations and genomic instability in advanced NSCLC with brain metastases, where EGFR and ALK alterations are linked to better survival. In contrast, high genomic complexity is associated with worse outcomes.

Driver gene mutations are present in more than half of the patients with central nervous system (CNS) failure. Genomic instability, characterized by the number of co-occurring mutated genes and copy-number alterations, is a risk factor associated with shorter survival time.

Ovarian clear cell carcinoma (OCCC) accounts for about 5% of all epithelial ovarian cancers. Currently, its treatment mainly refers to high-grade serous carcinoma (HGSC). This study aimed to explore differences in clinical characteristics between OCCC and HGSC and studied the reasons for the differences.

The data of OCCC and HGSC cases were obtained from the SEER database. Univariate and multivariate Cox regression analyses were used to explore the prognostic factors. Next, whole exome sequencing (WES) was performed on 15 clinically selected OCCC cases and 16 HGSC cases to identify significantly mutated genes (SMGs). Further analysis included calculating tumor mutation burden (TMB) and predicting potential target drugs based on the identified mutations.

3493 OCCC and 10266 HGSC patients from the SEER database were included in the study. Survival analysis showed that the overall survival (OS) of stage I-II OCCC was better than that of stage I-II HGSC, while the OS of stage III-IV OCCC was worse than that of stage III-IV HGSC. Further subgroup analysis showed that for the OCCC group, age ≥ 60 years, bilateral tumor distribution, tumor size ≥ 87mm, and stage III-IV were independent risk factors for OS. For HGSC patients, tumor size ≥ 87mm was an independent protective factor for OS. WES results suggested that among the top 20 SMGs of OCCC in stage III-IV patients, DNAH2, LAMA5, MUC19, NOTCH1, PCLO, SYNE2, TACC2, and ZNF469 were 8 specific SMGs that distinguish III-IV OCCC from III-IV HGSC. In addition, the stage I-II OCCC group had the highest TMB, and the lowest was the stage III-IV OCCC.

Our findings challenge the conventional uniform therapeutic approach for ovarian carcinomas by revealing stage-dependent SMGs between OCCC and HGSC. However, limitations such as the retrospective SEER analysis, small WES cohort, and population-specific driver gene variations require cautious interpretation of the findings.

The independent prognostic factors identified in this study provide a theoretical basis for individualized prognosis judgment in OCCC and HGSC. The SMGs and TMB levels may serve as valuable indicators for prognosis and evaluating targeted therapy or immunotherapy efficacy. Druggable genes such as NOTCH1 and RYR3 offer promising therapeutic targets, while stage-specific pathway enrichments reveal potential intervention strategies. Further validation in larger cohorts is needed to confirm these findings. Our study advances the understanding of molecular heterogeneity in ovarian cancer and lays the groundwork for personalized treatment strategies, ultimately improving patient outcomes.

Colorectal cancer (CRC) is among the most widespread malignancies worldwide and is a leading cause for cancer mortality. The interstitial interaction between cancer and stem cells is important during cancer cell metastasis.

In this study, we aimed to elucidate the regulatory role and the underlying mechanisms controlling the activity of exosomes derived from cancer stem cells (CSCs).

Our group isolated exosomes from CSCs and non-CSCs to examine their regulatory mechanisms using Transwell migration, Cell Counting Kit-8 (CCK-8), and 5-ethynyl-2′-deoxyuridine (EdU) assays.

The role of Eukaryotic Translation Initiation Factor 3 Subunit B (EIF3B) in CRC was examined using an in vivo tumorigenesis mouse model. It was found that treatment with exosomes isolated from CD133⁺ cells (CD133+Exos) promoted the proliferation and migration of SW480 cells. The downregulation of EIF3B reduced the proliferation and migration-promoting effects of CD133⁺ Exos on SW480 cells. Furthermore, CD133⁺ Exos treatment promoted the tumorigenesis of SW480 cells.

Our findings demonstrate that CSC-derived exosomes transport EIF3B into CRC cells to initiate epithelial-to-mesenchymal transition (EMT) and promote metastasis.

Euphorbia humifusa Willd (EH) is a traditional medicinal herb in China. However, the anti-prostate cancer active compounds of EH and their molecular mechanisms have yet to be elucidated.

The peaks of EH water extract in the fingerprinting were analysed using liquid chromatography coupled to quadrupole time of flight mass spectrometry. The cell viability of 22RV1 cells was determined via MTT. The active compounds and potential targets were screened in silico. The prostate cancer-associated targets were collected from the GeneCards database. The herb-compound-target-disease (H-C-T-D) and PPI networks were constructed to predict key targets. The molecular docking analysis of the active compounds with key targets was conducted using Autodock Vina 1.1.2. Western blot analysis was performed to evaluate the protein expression.

LC-MS results demonstrated that EH water extract is a rich source of phenolics and flavonoids. EH water extract inhibited the viability of 22RV1 cells in a time-and dose-dependent manner. Moreover, the in silico screening results identified 17 active compounds from EH with 518 prostate cancer-related key genes. Moreover, an H-C-T-D network analysis combined with the PPI network results effectively identified seven chemical compounds, oestrogen receptor 1, and androgen receptor (AR) to be highly related to prostate cancer. Furthermore, molecular docking results showed that 4′,5-dihydroxyflavone, ensaculin, luteolin, hypolaetin, quercetin, and kaempferol had a strong binding affinity with AR. Finally, Western blot results demonstrated that EH water extract, quercetin, kaempferol, and luteolin significantly down-regulated the AR protein expression in 22RV1 cells.

These results suggest that EH may provide a new promising therapeutic for prostate cancer treatment.

This study aims to explore the potential mechanisms by which Raddeanoside R13 (R13) inhibits the proliferation, invasion, and metastasis of gastric cancer (GC) cells through network pharmacology analysis and experimental validation.

First, network pharmacology was used to explore the potential mechanisms of R13 in treating GC. The effects of R13 on GC cell proliferation were assessed using CCK-8 and colony formation assays. Apoptosis was measured by flow cytometry, while the effects of R13 on invasion and metastasis were evaluated through wound healing and Transwell invasion assays. Finally, Western blotting was performed to investigate the impact of R13 on the expression of epithelial-to-mesenchymal transition (EMT) markers, PI3K/AKT signaling pathway proteins, and apoptosis-related proteins in GC cells.

A total of 58 potential targets of R13 in the treatment of GC were identified. R13 was found to affect the development of GC by regulating pathways, such as NFKB1, mTOR, apoptosis, and the PI3K-AKT signaling pathway. In vitro experiments confirmed that R13 inhibited the proliferation, invasion, and metastasis of GC cells while promoting apoptosis. Additionally, we found that R13 suppressed the EMT of GC cells and reduced the phosphorylation levels of PI3K, AKT, and mTOR. When this pathway was activated, it partially reversed these effects.

R13 inhibited the proliferation, invasion, and metastasis of GC cells while inducing apoptosis. Furthermore, R13 may suppress the EMT process in GC cells by inhibiting the PI3K/AKT/mTOR signaling pathway. These findings provide a foundation for the potential use of R13 as a therapeutic strategy for GC.

Hepatocellular carcinoma (HCC) is a kind of fatal cancer with a variety of risk factors. However, a pan-etiology molecular characterization of HCC has not been explored.

The objective of this study is to explore etiology-specific features of HCC and improve our understanding of tumorigenesis, thereby revealing potential therapeutic targets.

RNA-seq, genetic alteration, copy number alteration, and clinicopathological data of The Cancer Genome Atlas -Liver Hepatocellular Carcinoma cohort were downloaded and explored. Immune-related features and single-cell and spatial transcriptomic data were adopted and analyzed.

Etiology-based analyses revealed that HCC with different etiologies showed different clinical features, including gender composition, ethnic composition, clinical stage distribution, and survival. In addition, distinct genetic alterations, copy number alterations, and tumor microenvironment were observed in HCC patients with different etiologies. Significantly enhanced expression of squalene epoxidase (SQLE) was observed in viral hepatitis-related HCC and was associated with poor tumor grade and overall survival. Correlation analysis revealed a negative relationship between SQLE expression and anti-tumor immunity. Single-cell and spatial transcriptomics demonstrated that SQLE contributed to reduced T cell and NK cell infiltration while increasing macrophage and monocyte infiltration.

The current study demonstrated that HCC has etiology-specific clinical features, genetic alteration, copy number alteration, and tumor microenvironment. Overexpression of SQLE in viral hepatitis-related HCC correlate with poor clinical outcome and may contribute to reduce T cell and NK cell infiltration while increased macrophage and monocyte infiltration, which lead to immunosuppressive microenvironment and can be an actionable target.

Cholangiocarcinoma (CC) is a rare, aggressive cancer of the bile ducts with limited treatment advancements over recent decades. The five-year survival rate for CC remains low, around 10%, and even lower for advanced cases.

This case report discusses a 46-year-old woman with metastatic CC who achieved remarkable progression-free survival with regorafenib, a multikinase inhibitor typically used in other cancers. After multiple lines of treatment, regorafenib was given as a 7th-line therapy. Despite initial intolerance requiring dose reduction, the patient achieved 22 months of progression-free survival (PFS) with stable disease and partial regression in some areas. Her response to regorafenib significantly exceeded typical outcomes in the literature, where PFS generally ranges from 3 to 4 months. This improvement may be attributed to an FGFR2 mutation identified via next-generation sequencing, which regorafenib may effectively target.

This case suggests that patients with FGFR2 mutations might benefit from regorafenib, warranting further studies to explore this associationAs can be applied as a promising target gene to develop drug resistance and remedial efficacy.

Gastric cancer is the third most lethal malignancy worldwide. While cisplatin has shown remarkable efficacy at a low cost, it is also associated with severe side effects. Exosomes play a key role in mediating the bystander effect of radiation and have the capacity to deliver apoptosis signals for targeted destruction of tumor cell. However, there remains a paucity of research on exosome-mediated bystander effects in the context of chemotherapeutic drugs.

This study aims to investigate the ability of cisplatin-induced exosomes to deliver apoptosis signals to gastric cancer cells, with the aim of mitigating the adverse effects associated with chemotherapy.

Differential ultracentrifugation was used to isolate apoptotic exosomes secreted by cisplatin-induced gastric cancer MKN-28 cells. Characterization and identification of these exosomes were performed by transmission electron microscopy, particle size analyzer, flow cytometry, and Western blotting. The transduction efficiency of the exosomes was confirmed through immunefluorescence. The effects of apoptotic exosomes on the proliferation, apoptosis, migration, cycle, senescence, and tumor formation of MKN-28 cells in vitro and in vivo were investigated by live cell workstation, flow cytometry, HE staining, and tumorigenicity assays.

Cisplatin-induced apoptotic exosomes, termed DDP-EXO, exhibited a significantly enhanced inhibitory effect on the proliferation of MKN-28 cells compared to gastric epithelial GES-1 cells. Moreover, DDP-EXO was able to deliver apoptotic signals to MKN-28 cells, leading to an increase in the apoptotic population in recipient cells, possibly through the involvement of Caspase-9. Furthermore, DDP-EXO showed limited impacts on cell migration, cell cycle, or cell senescence. In vivo, DDP-EXO effectively suppressed tumorigenesis in a subcutaneous tumor model without causing detectable pathological changes in main organs and blood samples, suggesting a favorable safety profile.

In summary, this study provides new perspectives on the potential application of exosomes as an innovative therapeutic approach for gastric cancer.