Cancer Therapy Research Articles

Innovative logic “AND” gate gene circuits for bladder cancer treatment: preclinical study

In the evolving field of precision oncology, the synthesis of gene circuits that specifically target cancer cells while preserving normal tissue marks a significant breakthrough. However, traditional approaches typically concentrate on single-gene targets, lacking the directed recognition and control among the intricate networks of signaling pathways. Our study presents a synthetic gene circuit, the Logic “AND” Gate Dual-Target Genetic Circuit (LAG-DTGC), which integrates multiple signals to achieve comprehensive reprogramming of various signaling pathways in bladder cancer (BC) cells. This circuit’s development hinged on detailed bioinformatics analysis, pinpointing more unique biomarkers with similar expression pattern in BC. LAG-DTGC is engineered to selectively activate in cells where these biomarkers are abnormally expressed. Its precision and the remodeling cell behavior capability are further enhanced by incorporating a logic “AND” gate, triggering the circuit only in the presence of these aberrant cancer-specific biomarkers. LAG-DTGC exhibits an extraordinary ability to reprogram cancer cell signaling pathways, turning the cells’ own mechanisms against them for therapeutic effect. This work highlights the potential of synthetic biology in developing precise, less toxic treatments for BC. The LAG-DTGC represents a promising new paradigm in cancer therapy.

Nanotechnology in Cancer Treatment: Innovative Approaches to Overcoming Drug Resistance in Tumors

Nanotechnology has emerged as a groundbreaking approach in oncology, offering innovative solutions to one of the most significant challenges in cancer treatment: drug resistance. This literature review explores the role of nanotechnology in overcoming multidrug resistance (MDR) in tumors, focusing on the use of nanoparticles for targeted drug delivery, gene therapy, and immunotherapy. By penetrating biological barriers and modulating the tumor microenvironment, nanocarriers enhance the efficacy of anticancer agents while minimizing side effects. Additionally, this review provides a comprehensive analysis of recent clinical trials, offering insights into the real-world effectiveness of nanotechnology-based treatments. Ethical, regulatory challenges, and nanotoxicity are discussed to ensure the safe translation of nanomedicine to clinical practice. The review concludes with future directions in personalized nanomedicine, highlighting nanotechnology’s transformative potential in revolutionizing cancer treatment and improving patient outcomes by addressing the pervasive issue of drug resistance.Keywords: nanotechnology, drug resistance, nanoparticles, targeted drug delivery, cancer therapy.

Size-dependent dose estimation applied to 177Lu and 90Y -DOTATATE using ICRP Phantoms Nuclear Science and Engineering

Purpose: radiolabeled peptide has attracted growing interests for neuroendocrine cancer therapy. We aim to calculate S-values of Lu-177, In-111 and Y-90 in different size of International commission of radiation protection (ICRP) male and female phantoms for pre-estimation of absorbed dose in critical target organs using Monte Carlo simulation to see the extent of difference. Materials and methods: We employed the most advanced hybrid ICRP phantom and used its different male and females BMIs to resemble reality. Twenty different size of ICRP male and female phantoms were generated. GATE code was used to perform dosimetry calculations. Spline, bladder, kidneys, and liver were chosen as the source organs and the S- values were calculated in interested target organs for twenty different body mass indexes (BMIs). Results: The S-values in both self-absorptions and target organs were dramatically lower for 177Lu -DOTATATE compared to 90Y-DOTATATE. The highest difference between the absorption in kidneys is for BMI of 24.3. The highest S-value in bladder from bladder is 0.01 mGy/MBq.s in BMI of 34.4 for 177Lu-DOTATATE, whereas it is 0.0049 mGy/MBq.s in BMIs of 34.4 for 90Y-DOTATATE. It was found that dose per unit cumulated activity had a tendency to decrease with BMI. Conclusion: Variability in 177Lu -DOTATATE and 90Y-DOTATATE dosimetry across morphometrically different patients are important in optimizing therapy protocols and research studies. Using size-dependent phantoms for dosimetry, estimations more accurate dose per cumulated activity relative to standard reference dosimetry. To prevent excessive dosage to patients, it is important to consider the relationship between body size and dose.

Mechanistic insights into the anticancer, anti-inflammatory, and antioxidant effects of yellowfin tuna collagen peptides using network pharmacology

Marine-derived collagen peptides have been acknowledged for their therapeutic potential, especially in cancer therapy and inflammation management. The aim of this study was to investigate the molecular mechanisms that contribute to the anticancer, anti-inflammatory and antioxidant properties of yellowfin tuna collagen peptides (YFTCP) utilizing a network pharmacology approach. The YFTCP was extracted from the bones of yellowfin tuna (Thunnus albacares) and subsequently hydrolyzed with trypsin. Seventeen peptides were discovered using liquid chromatography in conjunction with high-resolution mass spectrometry (LC-HRMS). A network pharmacology method was utilized to investigate the interactions between the discovered peptides and their biological targets. Additionally, gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses were performed to identify pertinent biological pathways involved in the anticancer, antioxidant, and anti-inflammatory effects of these peptides. GO analysis revealed key associations between YFTCP and critical cancer- and inflammation-related genes encoding proteins such as CCND1, SRC, AKT1, IL-1β, TNF, and PPARG, which exhibited significant interactions. These proteins are essential for the regulation of the cell cycle, the development of tumors, and the response to inflammatory stimuli. The KEGG analysis also revealed that YFTCP was involved in a number of critical pathways, such as endocrine resistance, cancer pathways, Kaposi sarcoma-associated herpesvirus infection, proteoglycans in cancer, and human cytomegalovirus infection. These findings highlight the potential use of YFTCP as a multifaceted therapeutic agent, indicating their role in regulating important biological pathways associated with cancer development and inflammation. This study provides new valuable insights into the pharmacological properties of YFTCP, paving the way for future studies and drug development focused on these bioactive peptides.

Design and application of ferritin-based nanomedicine for targeted cancer therapy.

Owing to its unique structure and favorable biocompatibility, ferritin has been widely studied as a promising drug carrier over the past two decades. Since the identification of its inherent tumor-targeting property due to unique recognition ablity of the transferrin receptor 1 (TfR1), ferritin-based nanomedicine has attracted widespread attention and triggered a research surge in the field of targeted cancer therapy. Along with progress in structure studies and modification technology, diverse strategies have been carried out to equip ferritin with on-demand functions, further improving the antitumor efficacy and in vivo safety of ferritin-based cancer therapy. In this review, we highlight the structure-based rational design of ferritin and summarize the design strategies in detail from two main perspectives: multifunctional modification and drug loading. In particular, the critical issues that need attention in the design are discussed in depth. Furthermore, we provide an overview of the latest advances in the application of ferritin-based nanomedicines in chemotherapy, phototherapy and immunotherapy, with particular emphasis on emerging therapeutic approaches among these therapies.

Stimulus-activated ribonuclease targeting chimeras for tumor microenvironment activated cancer therapy

RNA degradation using ribonuclease targeting chimeras (RiboTACs) is a promising approach for cancer therapy. However, potential off-target degradation is a serious issue. Here, a RiboTAC is designed for tumor microenvironment triggered activation. The tumor microenvironment activated RiboTAC (TaRiboTAC) incorporates two pre-miR-21 binders, a near-infrared fluorophore IR780, an RGD targeting peptide and a phenylboronic acid caged ribonuclease recruiter. The caged ribonuclease recruiter is embedded in the molecule and exposed in acidic pH, the phenylboronic acid cage is removed by H2O2 making the TaRiboTAC responsive to the acidic and high H2O2 levels in the tumor microenvironment. It is shown the TaRiboTAC targets tumor tissue and degrades pre-miR-21. The degradation of pre-miR-21 by TaRiboTACs significantly increases the radiotherapeutic susceptibility of cancer cells achieving efficient suppression of human lung adenocarcinoma A549 tumors in living mice.

Thiazolidinedione derivatives: emerging role in cancer therapy.

Cancer remains the leading cause of death worldwide, with the Globocan 2022 study reporting an estimated 9.7 million cancer deaths. Without the selectivity built for tumour cells, chemotherapeutic agents could be toxic to non-cancerous cells. Administration of such non-selective cytotoxic compounds causes severe side effects and could lead to death. Improved cancer treatments are required to overcome the limitations of the current cancer treatment. The potential of thiazolidinedione derivatives as anticancer drugs has recently drawn attention, despite their primary use as insulin sensitizers in the treatment of type 2 diabetes. The ability of thiazolidinedione derivatives to alter important molecular pathways implicated in carcinogenesis, such as cell proliferation, apoptosis, angiogenesis, Raf kinase, EGFR and HER-2 kinases, HDAC, COX-2 enzyme and metastasis, is highlighted in this review, which examines the growing relevance of these compounds in cancer treatment. Thiazolidinediones have anti-inflammatory, antioxidant, and antiproliferative properties in a variety of cancer types, including breast, colon, and prostate cancers, via activating the peroxisome proliferator-activated gamma receptor (PPARγ). In addition to examining the safety profile and difficulties in clinical translation, the paper looks at preclinical and clinical research that points to these medicines potential to improve the effectiveness of immunotherapy and chemotherapy. This review highlights the encouraging therapeutic possibilities and structure-activity relationship insight of TZDs for their anticancer activity and highlights the molecular level facets of the 'glitazone' pharmacophore for its anticancer activity.

Cardiac CT reveals high prevalence of coronary artery disease in esophageal cancer eligible for radiotherapy.

Assessment of cardiac disease before cancer therapy is crucial, as advancements in cancer treatment have led to prolonged survival and an increase in cardiovascular complications. Specifically, esophageal cancer and heart disease share common risk factors, such as smoking and obesity. Radiation therapy (RT) for esophageal cancer is associated with elevated cardiac radiation exposure. This study aimed to assess the prevalence of coronary artery disease (CAD) in patients with esophageal cancer who were eligible for RT. We examined the prevalence of coronary artery stenosis, abnormal myocardial perfusion, and late enhancement using pre-RT cardiac computed tomography (CT) data of 41 patients with thoracic esophageal cancer who were referred for RT between January 2017 and June 2023 and had no history of ischemic heart disease. The median age of the 41 patients was 71 years, with 40 patients being male. Cardiac CT identified significant coronary stenosis (≥50% luminal narrowing) in 18 patients (44%), among whom 9 (50%) had severe stenosis, multivessel disease, or myocardial ischemia. Significant stenosis was most frequently observed in the left anterior descending artery (16/18). Late enhancement, indicating myocardial infarction, was observed in seven patients (17%). Patients with esophageal cancer without a history of ischemic heart disease had a high prevalence (44%) of CAD, with half of them having severe stenosis, multivessel disease, or myocardial ischemia. Given the high prevalence of coronary stenosis, pre-treatment cardiac evaluation is crucial for patients with esophageal cancer. Incorporating cardiac CT findings into radiotherapy planning is recommended to optimize patient care.

Mucoadhesive Xanthan-Carrageenan Hydrogel: a Nanocomposite Dosage Form with Sesame Components Designed for Local Therapy of Cervical Cancer

Mucoadhesive Xanthan-Carrageenan Hydrogel: a Nanocomposite Dosage Form with Sesame Components Designed for Local Therapy of Cervical Cancer

Mechanistic Approach into 1,2,3-triazoles-based IIIM(S)-RS98 Mediated Apoptosis in Lung Cancer Cells.

Lung cancer is a major public health problem across the globe, since it is the second most frequent cancer and the leading cause of cancer fatalities. This necessitates careful assessment of current therapies for lung cancer and discovery of novel drug candidates. 1,2,3 triazole compounds have emerged as an important class of prospective chemotherapeutic drugs for the treatment of lung cancer, with promising anti-lung cancer activity shown via a variety of pathways. They may interact with a various enzymes and receptors in cancer cells, causing cell cycle arrest and the activation of apoptosis. The present study aims to investigate the cytotoxic potential of institutional molecule based on 1,2,3 triazole [IIIM(S)-RS98] on multiple cancer cell lines. The compound was found to be most active on A549 cells and displayed the selectivity index as 8.16 in normal cells (e.g. HEK293). The in vitro findings revealed that IIIM(S)-RS98 induced apoptosis, loss of mitochondrial membrane potential, enhanced ROS and nitric oxide levels, and arrest cells in the G1 phase of the cell cycle. It inhibits the cell migration and clonogenic potential of A549 cells. Additionally, the downregulation of PI3K and p-Akt pathway leads to the activation of pro-apoptotic proteins Bax, downregulation of bcl2, activation of caspase 9, cleaved caspase 3, and cleaved parp1 expression and finally contribute towards apoptosis. Furthermore, molecular docking analysis indicated the interactions of IIIM(S)-RS98 with the apoptotic target proteins. The results demonstrated the potential of IIIM(S)-RS98 in the therapy of lung cancer.

Development of a prognostic model based on four genes related to exhausted CD8+ T cell in triple-negative breast cancer patients: a comprehensive analysis integrating scRNA-seq and bulk RNA-seq.

Low immune infiltration is closely associated with poor clinical results and an unfavorable response to therapy in triple-negative breast cancer (TNBC). T-cell exhaustion (TEX) is a significant risk factor for tumor immunosuppression and invasion. Although improving TEX and enhancing effector function are promising strategies for strengthening immunotherapy, their role in the pathogenesis of TNBC remains unclear. This study's objective was to develop a prognostic model for TNBC based on exhausted CD8+ T-cell (CD8+ Tex)-related differentially expressed genes(DEGs) and to investigate its clinical and immune relevance. Initially, 398 CD8+ Tex-related genes were screened utilizing single-cell RNA sequencing (scRNA-seq) data from TNBC patients. Pseudotime analysis confirmed that CD8+ Tex mainly clustered at the end of the differentiation pathways, making them a critical subset in TNBC progression. By analyzing the TCGA cohort, ten CD8+ Tex-related DEGs were identified assignificantly correlated with overall survival (OS) in TNBC patients, and a prognostic model containing four biomarkers (GBP1, CTSD, ABHD14B, andHLA-A) was constructed. The model demonstrated robust predictive capability in both the TCGA cohort and an external cohort, with the low-risk group exhibiting elevated expression of immunological checkpoint molecules and immune cell infiltration, as well as better responses to immunotherapy and chemotherapy. Furthermore, these four biomarkers were found to be highly expressed on CD8+ Tex and were associated with cellular communication efficiency. Therefore, this model is expected to be a new method for forecasting TNBC patients' prognosis and effectiveness of treatment, providing new insights for clinical decision-making.

Claudin 18.2 Immunohistochemistry Expression in Gastric Cancer: A Systematic Review.

Claudin 18.2 is a transmembrane protein, part of the tight-junction complex, selectively expressed in gastric epithelium. It is showing promising results as a target in advanced gastric cancer in phase 3 clinical trials using a monoclonal antibody against claudin 18.2. A systematic review on expression of claudin 18.2 in gastric cancer was performed using the PubMed database. The following search expression was used: ("Stomach Neoplasms" [Mesh]) AND (("claudin-18[TIAB]") OR ("CLDN18[TIAB]")). A total of n=99 articles were retrieved. Of those, 17 preclinical studies about claudin 18.2 expression by immunohistochemistry were selected. The results of those studies showed great variability in the criteria used for defining the thresholds for positivity of the stain. The proportion of claudin 18.2 positive cases varied between 24% and 83%. In works using a positivity threshold set at >40% or >70% of cells with membranous/cytoplasmic staining at 2+/3+ intensity, the average rate of positive cases was 50% or 30%, respectively (similar with clones 43-14A and EPR19202). Positivity of claudin 18.2 was associated with advanced stage, diffuse phenotype and PD-L1 and EBV positivity in some of the studies. Variability in criteria used to define claudin 18.2 positivity, as well as methodological differences, could explain the variation in the proportion of positive cases described, as well as the inconsistency of the association with clinical, molecular, and survival variables. The upcoming anticlaudin 18.2 therapy in advanced gastric cancer should prompt pathology laboratories to adjust their staining protocols and evaluation criteria in their series of patients, to further establish the association of claudin expression with clinical and molecular variables.

Probiotic-Derived Metabolites from Lactiplantibacillus plantarum OC01 Reprogram Tumor-Associated Macrophages to an Inflammatory Anti-Tumoral Phenotype: Impact on Colorectal Cancer Cell Proliferation and Migration

Background: Tumor-associated macrophages (TAMs) are key players in the colorectal cancer (CRC) tumor microenvironment (TME), representing the most abundant immune cells within it. The interplay between the intestinal microbiota, macrophages, and cancer cells significantly impacts tumor progression by driving macrophage polarization. Particularly, the polarization into the pro-tumoral M2-like TAM phenotype promotes the extracellular matrix remodeling, cancer cell proliferation, metastasis, immune suppression, and therapy resistance. Probiotic metabolites can disrupt this crosstalk, possibly reverting the TAM polarization toward a pro-inflammatory anti-tumoral phenotype, thus potentially benefiting the intestinal mucosa and opposing CRC progression. Previously, we showed that Lactiplantibacillus plantarum OC01 metabolites counter interleukin (IL)-6-induced CRC proliferation and migration. Methods: Here, we explore how probiotics affect CRC secretome and how this influences TAM polarization, which then impacts CRC malignancy. Results: The conditioning medium (CM) from CRC cells indeed promoted the polarization of macrophage toward the M2-like phenotype, whereas the CM from CRC pre-treated with L. plantarum OC01 metabolites induced a pro-inflammatory macrophage phenotype, characterized by NLRP3 inflammasome activation and reactive oxygen species (ROS) production, and by decreased expression of the M2 phenotype markers CD206 and CD163. Consistently, the expression of tumor growth factor (TGF)-β, a promoter of M2 macrophage polarization, was reduced in CRC cells treated with L. plantarum OC01. The pro-inflammatory macrophages inhibited CRC proliferation and migration. Conclusions: Overall, our study highlights the potential of metabolites from L. plantarum OC01 to reprogram the metabolism in cancer cells and thus reshape the TME by shifting TAMs toward a more inflammatory and anti-tumoral phenotype, emphasizing the promise of probiotics in advancing novel therapeutic approaches for CRC.

Aggregation-Mediated Photoacoustic/NIR-II and Photodynamic Properties of pH-Reversible Thiopyrylium Agents: A Computational and Experimental Approach.

Aggregation profoundly influences the photophysical properties of molecules. Here, a new series of thiopyrylium-based hemicyanine near-infrared II (NIR-II) fluorophores is developed by meticulously adjusting their aggregation states. Notably, the star molecule HTPA exhibits a remarkable pH-responsive behavior and a significant increase in photoacoustic (PA) intensity when aggregated. Additionally, their behavior and pH reversibility during aggregation formation are systematically investigated, including computational optimization, femtosecond transient absorption spectroscopy, NMR analysis, and single crystal analysis. Finally, an innovative "off " nanoparticle specifically is designed for effective tumor-targeted PA/NIR-II dual-modal imaging and photodynamic therapy by utilizing a pH-responsive polymer. The signal-to-background ratio (SBR) of PA signals significantly increased to 169 in the region of interest (ROI) in the mouse model when irradiated at 1064nm. These findings not only provide a promising avenue for future studies of NIR-II small molecules but also pave the way for significant advances in the field of integrated cancer diagnosis and therapy.

Translational regulation of SND1 governs endothelial homeostasis during stress.

Translational control shapes the proteome and is particularly important in regulating gene expression under stress. A key source of endothelial stress is treatment with tyrosine kinase inhibitors (TKIs), which lowers cancer mortality but increases cardiovascular mortality. Using a human induced pluripotent stem cell-derived endothelial cell (hiPSC-EC) model of sunitinib-induced vascular dysfunction combined with ribosome profiling, we assessed the role of translational control in hiPSC-ECs in response to stress. We identified staphylococcal nuclease and tudor domain-containing protein 1 (SND1) as a sunitinib-dependent translationally repressed gene. SND1 translational repression was mediated by the mTORC1/4E-BP1 pathway. SND1 inhibition led to endothelial dysfunction, whereas SND1 OE protected against sunitinib-induced endothelial dysfunction. Mechanistically, SND1 transcriptionally regulated UBE2N, an E2-conjugating enzyme that mediates K63-linked ubiquitination. UBE2N along with the E3 ligases RNF8 and RNF168 regulated the DNA damage repair response pathway to mitigate the deleterious effects of sunitinib. In silico analysis of FDA-approved drugs led to the identification of an ACE inhibitor, ramipril, that protected against sunitinib-induced vascular dysfunction in vitro and in vivo, all while preserving the efficacy of cancer therapy. Our study established a central role for translational control of SND1 in sunitinib-induced endothelial dysfunction that could potentially be therapeutically targeted to reduce sunitinib-induced vascular toxicity.

Lactoferrin-Derived Peptide Chimera Induces Caspase-Independent Cell Death in Multiple Myeloma

Lactoferrin-derived peptide chimera is a synthetic peptide that mimics the functional unit of lactoferrin with antibacterial activity. Although LF has anticancer effects, to the best of our knowledge, its effects on multiple myeloma have not yet been studied. We explored the potential of a lactoferrin-derived chimera for multiple myeloma treatment, a malignant clonal plasma cell bone marrow disease. The lactoferrin-derived chimera effectively inhibited MM1S, MM1R, and RPMI8226 multiple myeloma cell growth, and induced the early and late phases of apoptosis, but not in normal peripheral blood mononuclear cells. Furthermore, the lactoferrin-derived chimera modulates the relative expression of genes involved in survival, apoptosis, and mitochondrial dysfunction at the transcriptional level. Mitochondrial analysis revealed that lactoferrin-derived chimera triggered oxidative stress in multiple myeloma cells, leading to reactive oxygen species generation and a decline in mitochondrial membrane potential, resulting in mitochondrial dysfunction. Although lactoferrin-derived chimera did not cause caspase-dependent cell death, it induced nuclear translocation of apoptosis-inducing factor and endonuclease G, indicating the initiation of caspase-independent apoptosis. Overall, the lactoferrin-derived chimera induces caspase-independent programmed cell death in multiple myeloma cell lines by increasing the nuclear translocation of apoptosis-inducing factor/endonuclease G. Therefore, it has potential for multiple myeloma cancer therapies.

Cellular Epigenetic Targets and Epidrugs in Breast Cancer Therapy: Mechanisms, Challenges, and Future Perspectives

Breast cancer is the most common malignancy affecting women, manifesting as a heterogeneous disease with diverse molecular characteristics and clinical presentations. Recent studies have elucidated the role of epigenetic modifications in the pathogenesis of breast cancer, including drug resistance and efflux characteristics, offering potential new diagnostic and prognostic markers, treatment efficacy predictors, and therapeutic agents. Key modifications include DNA cytosine methylation and the covalent modification of histone proteins. Unlike genetic mutations, reprogramming the epigenetic landscape of the cancer epigenome is a promising targeted therapy for the treatment and reversal of drug resistance. Epidrugs, which target DNA methylation and histone modifications, can provide novel options for the treatment of breast cancer by reversing the acquired resistance to treatment. Currently, the most promising approach involves combination therapies consisting of epidrugs with immune checkpoint inhibitors. This review examines the aberrant epigenetic regulation of breast cancer initiation and progression, focusing on modifications related to estrogen signaling, drug resistance, cancer progression, and the epithelial–mesenchymal transition (EMT). It examines existing epigenetic drugs for treating breast cancer, including agents that modify DNA, inhibitors of histone acetyltransferases, histone deacetylases, histone methyltransferases, and histone demethyltransferases. It also delves into ongoing studies on combining epidrugs with other therapies and addresses the upcoming obstacles in this field.

Machine learning-based screening and molecular simulations for discovering novel PARP-1 inhibitors targeting DNA repair mechanisms for breast cancer therapy.

Cancer remains one of the leading causes of death worldwide, with the rising incidence of breast cancer being a significant public health concern. Poly (ADP-ribose) polymerase-1 (PARP-1) has emerged as a promising therapeutic target for breast cancer treatment due to its crucial role in DNA repair. This study aimed to discover novel, targeted, and non-toxic PARP-1 inhibitors using an integrated approach that combines machine learning-based screening, molecular docking simulations, and quantum mechanical calculations. We trained a widely used machine learning models, Random Forest, using bioactivity data from known PARP-1 inhibitors. After evaluating the performance, it was used to screen an FDA-approved drug library, successfully identifying Atazanavir, Brexpiprazole, Raltegravir, and Nisoldipine as potential PARP-1 inhibitors. These compounds were further validated through molecular docking and all-atom molecular dynamics simulations, highlighting their potential for breast cancer therapy. The binding free energies indicated that Atazanavir at -41.86kJ/mol and Brexpiprazole at -45.44kJ/mol exhibited superior binding affinity compared to the control drug at -30.42kJ/mol, highlighting their promise as candidates for breast cancer therapy. Subsequent optimized geometries and electron density mappings of the two molecular structures revealed a Gibbs free energy of -2334.610 Ha for the first molecule and -1682.278316 Ha for the second, confirming enhanced stability compared to the standard drug. This study not only highlights the efficacy of machine learning in drug discovery but also underscores the importance of quantum mechanics in validating molecular stability, setting a robust foundation for future pharmacological explorations. Additionally, this approach could revolutionize the drug repurposing process by significantly reducing the time and cost associated with traditional drug development methods. Our results establish a promising basis for subsequent research aimed at optimizing these PARP-1 inhibitors for clinical use, potentially offering more effective treatment options for breast cancer patients.

Synthesis, biological evaluation, and molecular docking of ent-sauchinone-based amide derivatives with potential anti-invasion and anti-migration activities.

Ent-Sauchinone is a bioactive lignan isolated from Saururus chinensis (Lour.) Baill could suppress the migration and invasion of hepatocellular carcinoma (HCC) cells. The study involves the structural modification of ent-sauchinone to augment its inhibitory effect on HCC progression and to investigate the mechanisms involved. In this study, a series of ent-sauchinone based amide derivatives were synthesised and the anticancer activities were evaluated against two hepatoma cell lines. Among them, compound 3 exhibited excellent resistance to migration and invasion by reversing the epithelial-mesenchymal transition (EMT) and inhibiting the phosphorylation of signal transducer and activator of transcription 3 (STAT3) and the expression of matrix metalloproteinases (MMPs). Molecular docking results indicate that compound 3 may exert its inhibitory effect on the progression of liver cancer by acting on the DNA-binding domain of STAT3. These results suggested that compound 3 could be a potential anticancer agent, especially for metastatic cancer therapy.

Breaking barriers: Smart vaccine platforms for cancer immunomodulation.

Despite significant advancements in cancer treatment, current therapies often fail to completely eradicate malignant cells. This shortfall underscores the urgent need to explore alternative approaches such as cancer vaccines. Leveraging the immune system's natural ability to target and kill cancer cells holds great therapeutic potential. However, the development of cancer vaccines is hindered by several challenges, including low stability, inadequate immune response activation, and the immunosuppressive tumor microenvironment, which limit their efficacy. Recent progress in various fields, such as click chemistry, nanotechnology, exosome engineering, and neoantigen design, offer innovative solutions to these challenges. These achievements have led to the emergence of smart vaccine platforms (SVPs), which integrate protective carriers for messenger ribonucleic acid (mRNA) with functionalization strategies to optimize targeted delivery. Click chemistry further enhances SVP performance by improving the encapsulation of mRNA antigens and facilitating their precise delivery to target cells. This review highlights the latest developments in SVP technologies for cancer therapy, exploring both their opportunities and challenges in advancing these transformative approaches.