Efficacy Of Cancer Treatment Research Articles

Computational Exploration of a Diverse Flavonoid Library for Targeted Allosteric Inhibition of AKT1 in Cancer Therapy.

AKT serine/threonine kinase 1 (AKT1) is an established therapeutic target in cancer therapy due to its role in promoting cell survival and proliferation. This study aimed to identify potential allosteric inhibitors of AKT1 from a large flavonoid library using computational methods. A computational screening of a comprehensive flavonoid library to identify novel allosteric inhibitors targeting the AKT1 allosteric site was performed. Molecular docking identified compounds with favorable binding interactions and the top 10 were selected for binding pose analysis. Molecular dynamics simulations for 200 ns were further employed to assess the stability of the highest-ranked compound. The study proposed 10 flavonoids as potential allosteric AKT1 inhibitors. The docking analysis highlighted critical interactions between the 10 flavonoids and AKT1, with residues such as Trp-80, Ile-84, Tyr-272, Arg-273 and Asp-292 playing significant roles in binding stability. Trp-80 emerged as a pivotal residue, consistently forming the highest number of non-bonding contacts across most compounds, corresponding with prior studies that identified it as essential for allosteric inhibition. The highest-ranked flavonoid, CID 108790283, demonstrated the strongest binding affinity, with a binding energy of -10.64 kcal/mol, 56 non-bonding contacts, and a hydrogen bond. Molecular dynamics simulations further confirmed the stability of this flavonoid within the allosteric site, exhibiting minimal conformational fluctuation throughout the 200-ns simulation. This computational investigation identified 10 flavonoids with strong interaction profiles and stable binding within the allosteric site of AKT1, suggesting their potential as novel AKT1 inhibitors. These findings provide a basis for further experimental studies to validate their efficacy in cancer treatment.

Microbial molecules, metabolites, and malignancy.

Research elucidating the role of the microbiome in carcinogenesis has grown exponentially over the past decade. Initially isolated to associative studies on colon cancer development, the field has expanded to encompass nearly every solid and liquid malignancy that may afflict the human body. Investigations are rapidly progressing from association to causation and one particular area of causal effect relates to microbial metabolites and how they influence cancer development, progression, and treatment response. These metabolites can be produced de novo from individual members of the microbiome, whether that be bacteria, fungi, archaea, or other microbial organisms, or they can be through metabolic processing of dietary compounds or even host-derived molecules. In this review, contemporary research elucidating mechanisms whereby microbial-derived molecules and metabolites impact carcinogenesis and cancer treatment efficacy will be presented. While many of the examples focus on bacterial metabolites in colon carcinogenesis, this simply illustrates the accelerated nature of these investigations that occurred early in microbiome research but provides an opportunity for growth in other cancer areas. Indeed, research into the interaction of microbiome-derived metabolites in other malignancies is growing as well as investigations that involve non-bacterial metabolites. This review will provide the reader a framework to expand their knowledge regarding this complex and exciting field of cancer research.

Preliminary result of a phase Ib study: Efficacy and safety of FG-M108 plus gemcitabine/nab-paclitaxel as first-line (1L) treatment in patients with Claudin18.2-positive locally advanced unresectable or metastatic (LA/m) pancreatic cancer.

729 Background: FG-M108, an ADCC-enhanced anti-CLDN18.2 monoclonal antibody, showed significant efficacy in 1L treatment of gastric cancer. Herein, we report the safety and efficacy results of FG-M108 in 1L treatment of pancreatic cancer (cohort C2&D2). Methods: In this open-label, multicenter phase I/II study patients received FG-M108 (cohort C2: 300mg/m 2 or cohort D2: 600mg/m 2 Q3W) plus gemcitabine (1000mg/m 2 , d1, d8, Q3W) and nab-paclitaxel (125mg/m 2 , d1, d8, Q3W). Eligible patients were those with CLDN18.2 positive (IHC 1+/2+/3+≥10%) previously untreated LA/m pancreatic cancer. The primary endpoint were the incidence of adverse events (AEs) and preliminary clinical efficacy (ORR, DCR, DOR, PFS, and OS). Results: As of Sep 5 2024, 50 patients were enrolled and received FG-M108+gemcitabine/nab-paclitaxel treatment (39 patients in cohort C2, 11 patients in cohort D2). The median age was 61 (range 30-72). 47 (94%) patients were with CLDN18.2 moderate-high expression (IHC 2+/3+≥40%). Out of 50 patients, 44 patients had at least one tumor assessment after baseline and included in the efficacy analysis set. The results of ORR and DCR in cohort C2 were 32.4% and 100.0%, while that in cohort D2 were 30.0% and 90.0%, respectively. In cohort C2, the median PFS and median DOR were 6.8 months and 9.8 months, respectively. In the subgroup patients with CLDN18.2 moderate-high expression, the median PFS and median DOR were 7.6 months and 9.8 months, respectively. The median OS has not been reached. FG-M108 related AEs were observed in all patients, with 39 patients (78%) having Grade 3/4 AEs and no FG-M108 related fatal AE was observed. The most common FG-M108 related AEs in cohort C2 & D2 were anemia (56.2% vs 63.6%), nausea (56.4% vs 36.4%), vomiting (48.7% vs 45.5%), and hypoalbuminemia (46.2% vs 54.5%). Conclusions: The combined therapy of FG-M108 plus chemotherapy as 1L treatment for patients with CLDN18.2 positive pancreatic cancer was well tolerated with encouraging survival especially in patients with CLDN18.2 moderate-high expression, deserving further investigation. Clinical trial information: NCT04894825 .

Synthetic approaches and clinical applications of representative HDAC inhibitors for cancer therapy: A review.

Histone deacetylase (HDAC) inhibitors are a promising class of epigenetic modulators in cancer therapy. This review provides a comprehensive analysis of recent synthetic strategies and clinical applications of key HDAC inhibitors for oncology. HDACs play a critical role in modulating chromatin structure and gene expression by removing acetyl groups from histone proteins, leading to transcriptional repression of tumor suppressor genes. By inhibiting HDAC activity, HDAC inhibitors restore normal acetylation patterns, reactivating silenced tumor suppressor genes and inducing cell cycle arrest, apoptosis, and autophagy in cancer cells. The review explores synthetic approaches to developing representative HDAC inhibitors that have been approved or in various clinical trials. Through an integrated perspective on the synthesis, mechanism of action, and clinical advancements of HDAC inhibitors, this review aims to guide future research toward next-generation HDAC inhibitors that could enhance cancer treatment efficacy while minimizing toxicity, offering insights for chemists and clinicians in the field of oncology.

Exercise medicine as adjunct therapy during RADIation for CAncer of the prostaTE to improve treatment efficacy – protocol for the ERADICATE study: a phase II randomised controlled trial

BackgroundTumour hypoxia resulting from inadequate perfusion is common in many solid tumours, including prostate cancer, and constitutes a major limiting factor in radiation therapy that contributes to treatment resistance. Emerging research in preclinical animal models indicates that exercise has the potential to enhance the efficacy of cancer treatment by modulating tumour perfusion and reducing hypoxia; however, evidence from randomised controlled trials is currently lacking. The ‘Exercise medicine as adjunct therapy during RADIation for CAncer of the prostaTE’ (ERADICATE) study is designed to investigate the impact of exercise on treatment response, tumour physiology, and adverse effects of treatment in prostate cancer patients undergoing external beam radiation therapy (EBRT).MethodsThe ERADICATE study is a two-arm, parallel group, phase II randomised controlled trial. Fifty patients diagnosed with prostate cancer will be randomised (1:1) to either an exercise intervention group (EBRT + exercise) or a usual care control group (EBRT only) for the duration of treatment (i.e., 2 to 8 weeks of EBRT). The exercise intervention will be clinic-based and supervised by exercise physiologists. Exercise sessions will include moderate- to vigorous-intensity aerobic and resistance exercise conducted two to three times per week for 60 min per session. Treatment response (primary outcome) will be assessed by change in tumour apparent diffusion coefficient derived from magnetic resonance imaging. Secondary outcomes will include acute and chronic changes in tumour perfusion and hypoxia, treatment-related toxicity, body composition, physical function, and quality of life. Survival outcomes will be assessed as exploratory endpoints. Study measurements will be conducted at baseline (i.e., prior to commencing EBRT), immediately after completion of EBRT, and during follow-up at 3 months as well as 2 years and 5 years post treatment. The study was approved by the Human Research Ethics Committee at Edith Cowan University.DiscussionThe ERADICATE study will investigate exercise as a novel therapeutic approach for sensitising prostate cancer to EBRT by targeting a known mechanism of treatment resistance. Improving treatment efficacy of EBRT with exercise may result in better patient outcomes clinically, while also addressing adverse effects of treatment and quality of life in prostate cancer patients.Trial registrationThe study was registered on the Australian New Zealand Clinical Trials Registry (ACTRN12624000786594) on 26/06/2024.

Smart self-transforming nano-systems for overcoming biological barrier and enhancing tumor treatment efficacy.

Nanomedicines need to overcome multiple biological barriers in the body to reach the target area. However, traditional nanomedicines with constant physicochemical properties are not sufficient to meet the diverse and sometimes conflicting requirements during in vivo transport, making it difficult to penetrate various biological barriers, resulting in suboptimal drug delivery efficiency. Smart self-transforming nano-systems (SSTNs), capable of altering their own physicochemical properties (including size, charge, hydrophobicity, stiffness, morphology, etc.) under different physiological conditions, hold the potential to break through multiple biological barriers, thereby improving drug delivery efficiency and the efficacy of cancer treatment. In this review, we first summarize the design strategies of five most popular SSTNs (such as size-, charge-, hydrophilicity-, stiffness-, and morphology-self-transforming nano-systems), and then delve into their biomedical applications in enhancing circulation time, tissue penetration, and cellular uptake. Finally, we discuss the opportunities and challenges that SSTNs face in the future for cancer treatment and diagnosis.

Radiosensitization of Rare-Earth Nanoparticles Based on the Consistency Between Its K-Edge and the X-Ray Bremsstrahlung Peak

Nanoparticle-based X-ray radiosensitization strategies have garnered significant attention in recent years. However, the underlying mechanisms of radiosensitization remain incompletely understood. In this work, we explore the influence of the K-edge effect in the X-ray absorption of nanomaterials on sensitization. Due to the alignment of the K-edge of thulium (Tm) with the Bremsstrahlung peak in the energy spectrum of medical X-ray accelerators, the following four different rare-earth nanomaterials with varying Tm percentages were designed: NaTmF4, NaTm0.6Lu0.4F4, NaTm0.4Lu0.6F4, and NaLuF4. We evaluated the X-ray absorption and the ability to generate secondary electrons and reactive oxygen species (ROS) of these nanoparticles. The radiosensitizing effect was evaluated through clonogenic assays. Our results showed that the K-edge effect affected secondary electron generation but did not significantly change ROS production. Nonetheless, NaTmF4 induced marginally more DNA damage in the U87 cells than the other cell types. NaTmF4 also exhibited superior radiosensitization efficacy against the U87 tumor cells. This shows that secondary electrons and ROS play pivotal roles in radiosensitization, which might be crucial to improving cancer treatment efficacy through enhanced radiation therapy outcomes.

Targeted internalization and activation of glycosidic switch liposomes by a biological macromolecule mPEG×EphA2 increases therapeutic efficacy against lung cancer.

Glycosidic switch liposome (GSL) technology efficiently encapsulates and stabilizes potent anticancer drugs in liposomes using a reversible glucuronide ester. Enzymatic hydrolysis of the glucuronide switch in target cell lysosomes produces parental drug. Our study examined the potential of a bispecific macromolecule, a polyethylene glycol (PEG) engager (mPEG×EphA2), generated by fusing a humanized anti-methoxy PEG (mPEG) Fab with an anti-EphA2 single-chain antibody, to increase GSL uptake into cancer cells and boost the anticancer activity by targeting PEG on GSL and an internalizing tumor antigen. Combining GSL with the PEG engager creates αEphA2/GSL, targeting cancer cells to generate topoisomerase I poison 9-aminocamptothecin (9AC) for cell killing. Targeted liposomes can bind CL1-5 human lung adenocarcinoma cells and increase GSL internalization from 0% to 62.4% in 60min. αEphA2/GSL showed slightly higher cellular cytotoxicity than non-targeted GSL, but targeted GSL increased 9AC intratumoral concentrations by 8.4 fold at 24h. The 9AC tumor/blood ratio of αEphA2/GSL was nearly 6-fold higher than αDNS/GSL (control engager GSL). Using targeted GSL, five of seven mice with solid CL1-5 tumors were cured. The mPEG×EphA2 engager can enhance GSL drug uptake and generation, boosting lung cancer treatment efficacy, suggesting that αEphA2/GSL is a promising treatment for tumors overexpressing EphA2.

Ketogenic diet and cancer: multidimensional exploration and research.

The ketogenic diet (KD) has attracted attention in recent years for its potential anticancer effects. KD is a dietary structure of high fat, moderate protein, and extremely low carbohydrate content. Originally introduced as a treatment for epilepsy, KD has been widely applied in weight loss programs and the management of metabolic diseases. Previous studies have shown that KD can potentially inhibit the growth and spread of cancer by limiting energy supply to tumor cells, thereby inhibiting tumor angiogenesis, reducing oxidative stress in normal cells, and affecting cancer cell signaling and other processes. Moreover, KD has been shown to influence T-cell-mediated immune responses and inflammation by modulating the gut microbiota, enhance the efficacy of standard cancer treatments, and mitigate the complications of chemotherapy. However, controversies and uncertainties remain regarding the specific mechanisms and clinical effects of KD as an adjunctive therapy for cancer. Therefore, this review summarizes the existing research and explores the intricate relationships between KD and cancer treatment.

Effect of ultrasound combined with microbubbles therapy on tumor hypoxic microenvironment.

Tumor tissues exhibit significantly lower oxygen partial pressure compared to normal tissues, leading to hypoxia in the tumor microenvironment and result in resistance to tumor treatments. Strategies to mitigate hypoxia include enhancing blood perfusion and oxygen supply, for example,by decomposing hydrogen peroxide within the tumor. Improving hypoxia in the tumor microenvironment could potentially improve the efficacy of cancer treatments. Previous studies have demonstrated that ultrasound of appropriate intensity when combined with microbubbles, can improve tumor blood perfusion. However, its effects on tumor hypoxia remain unclear. This study aimed to assess the effects of low-frequency non-focused ultrasound combined with microbubbles at different intensities on tumor microenvironment hypoxia and to identify the optimal ultrasound parameters for alleviating tumor hypoxia. Rabbits with VX2 tumors received ultrasound and microbubble treatments at different acoustic pressures and pulse repetition frequencies. The changes in tumor tissue blood perfusion before and after treatment were observed by contrast enhanced ultrasound (CEUS). The changes in tumor tissue hypoxia before and after treatment were observed by measuring oxygen partial pressure directly with in tumor tissue and immunohistochemical staining for hypoxia-inducible factor-1α (HIF-1α). Results indicated that low frequency, non-focused ultrasound at 0.5MPa/20Hz and 0.5MPa/40Hz, when combined with microbubbles, could increase tumor tissue blood perfusion and improve the hypoxia in tumor tissues. This study provides a new method for improving hypoxia in the tumor microenvironment (TME) which could potentially improve the cancer treatments resistance.

Exploring the Potential of SGLT-2 Inhibitors in Cancer Treatment: Mechanisms, Preclinical Findings, and Clinical Implications

IntroductionSodium-glucose co-transporter 2 (SGLT-2) inhibitors, originally developed for the treatment of type 2 diabetes, have recently attracted attention for their potential applications in oncology. Their potential to modulate tumor metabolism and enhance responses to cancer therapies is an area of increasing interest. Aim of the studyThis review aims to explore the emerging role of SGLT-2 inhibitors in cancer treatment, focusing on their mechanisms of action, preclinical findings, and early clinical evidence. By understanding the potential of these agents to alter tumor metabolism and the immune microenvironment, we can evaluate their therapeutic value in cancer management. Material and MethodsData were gathered from peer-reviewed articles, clinical trials, and ongoing research on the use of SGLT-2 inhibitors in combination with chemotherapy, immunotherapy, and other cancer treatments. Description of the state of knowledgePreclinical studies suggest that SGLT-2 inhibitors can alter cancer cell metabolism by limiting glucose availability, potentially impeding tumor growth. These agents have demonstrated promise in models of breast, prostate, and pancreatic cancers, reducing cell proliferation and enhancing the efficacy of standard cancer treatments. ConclusionsSGLT-2 inhibitors represent a novel therapeutic strategy in oncology, with potential to improve outcomes in combination with traditional therapies. However, more extensive clinical trials are required to validate their effectiveness, optimize treatment regimens, and better understand their safety profiles in cancer patients.

Nanozyme-based synergistic therapeutic strategies against tumors.

Cancer remains a global health threat, with traditional treatments limited by adverse effects and drug resistance. Nanozyme-based catalytic therapy with high stability and controllable activity provides targeted and specific in situ tumor treatment to address these challenges. More intriguingly, the tremendous advances in nanotechnology have enabled nanozymes to rival the catalytic activity of natural enzymes, presenting an exciting opportunity for innovating antitumor nanodrugs. This review systematically summarizes the latest progresses in nanozyme-based anticancer catalytic therapy, with a particular focus on various synergistic antitumor strategies, including other functional enzymes, drugs, exogenous stimuli and radiotherapy. These combinations not only enhance the efficacy of cancer treatment and reduce systemic toxicity but also offer insights into the development of potent antitumor nanodrugs.

Harnessing HDAC-targeted oleanolic acid derivatives for combined anti-cancer and hepatoprotective effects.

The development of anti-tumor drugs with hepatoprotective properties has always been highly valued due to their dual capabilities of safeguarding the liver and combating tumors. Moreover, when used in conjunction with specific chemotherapy drugs, they can enhance the efficacy of cancer treatment while simultaneously reducing liver damage caused by chemotherapeutic agents. Our research focused on oleanolic acid (OA), a natural compound known for its liver-protective effects. By incorporating an HDAC-targeting pharmacophore at the 28-COOH site of OA, we aimed to identify compounds that offer dual benefits of liver protection and anti-tumor activity. Compound 2c demonstrated significant inhibitory effects on the growth of RS4;11, K562, and RPMI8226 cells, showed cytotoxicity against HepG2 liver cancer cells, and exhibited favorable selectivity towards normal liver cells. Moreover, compound 2c induced apoptosis in HepG2 cells and arrested cell cycle progression at the G2 phase. Further investigations revealed that compound 2c could alleviate cisplatin-induced liver cell damage and animal liver injury by activating the NRF2/HO-1 pathway. In a HepG2 xenograft model, intravenous administration of compound 2c effectively suppressed tumor growth without eliciting adverse reactions, while enhanced NRF2 and HO-1 expression was observed in the liver tissues of mice treated with compound 2c. Besides, co-administration of cisplatin with compound 2c could significantly enhance the anti-tumor efficacy of cisplatin but minimize liver injury caused by the treatment of cisplatin. Our study provides a lead compound possessing hepatoprotective and antitumor activity, offering a novel strategy to avoid pharmacological liver injury.

Polysaccharide-based drug delivery targeted approach for colon cancer treatment: A comprehensive review.

Colon cancer is a leading cause of cancer-related morbidity and mortality worldwide, necessitating advancements in therapeutic strategies to improve outcomes. Current treatment modalities, including surgery, chemotherapy, and radiation, are limited by systemic toxicity, low drug utilization rates, and off-target effects. Colon-targeted drug delivery systems (CDDS) offer a promising alternative by leveraging the colon's unique physiology, such as near-neutral pH and extended transit time, to achieve localized and controlled drug release. Polysaccharide-based CDDS, utilizing natural polymers like chitosan, cyclodextrin, pectin, guar gum, alginate, hyaluronic acid, dextran, chondroitin sulfate, and inulin, have emerged as innovative approaches for improving the specificity and efficacy of colon cancer treatments. These biocompatible and biodegradable polymers enable site-specific drug delivery, enhance tumor apoptosis, reduce systemic side effects, and improve patient compliance. This review evaluates recent advancements in polysaccharide-based CDDS, detailing their drug release mechanisms, therapeutic potential, and challenges in overcoming gastrointestinal transit and pH variability. Studies highlight the successful formulation of nanoparticles, microspheres, and other delivery systems, demonstrating targeted drug delivery, improved bioavailability, and enhanced cytotoxicity against colon cancer cells in-vitro and in-vivo. The review underscores the need for continued research on polysaccharide-based CDDS for colon cancer treatment, offering a path toward more effective, patient-centered oncological care.

Therapeutic Efficacy Studies on the Monoterpenoid Hinokitiol in the Treatment of Different Types of Cancer.

Hinokitiol (HK), a monoterpenoid that naturally occurs in plants belonging to the Cupressaceae family, possesses important biological activities, including an anticancer effect. This review summarizes its anticancer potential and draws possible molecular interventions. In addition, it evaluates the biopharmaceutical, toxicological properties, and clinical application of HK to establish its viability for future advancement as a dependable anticancer medication. The assessment is based on the most recent information available from various databases. Findings demonstrate that HK possesses substantial therapeutic advantages against diverse types of cancer (colon, cervical, breast, bone, endometrial, liver, prostate, oral, and skin) through various molecular mechanisms. HK induces oxidative stress, cytotoxicity, apoptosis, cell-cycle arrest at the G and S phases, and autophagy through modulation of phosphatidylinositol 3-kinase (PI3K)/Akt/mammalian target of rapamycin (mTOR), p38/ERK/MAPK, nuclear factor kappa B, and c-Jun N-terminal kinase signaling pathways. Furthermore, this compound exhibits good oral bioavailability with excellent plasma clearance. Clinical uses of HK demonstrate therapeutic advantages without any significant negative effects. A thorough study of the pertinent data suggests that HK may serve as a viable candidate for developing novel cancer therapies. Consequently, more extensive studies are necessary to evaluate its cancer treatment efficacy, safety, and possible long-term hazards.

Dual Targeting of MEK1 and Akt Kinase Identified SBL-027 as a Promising Lead Candidate to Control Cell Proliferations in Gastric Cancer.

Dual inhibition of Akt and MEK1 pathways offers a promising strategy to enhance treatment efficacy in gastric cancer. In this study, we employed computational approaches followed by in vitro validations. Our results demonstrate that SBL-027 exhibits robust and enduring interactions with Akt and MEK1 kinases, as evidenced by atomistic molecular dynamics simulations and molecular mechanics Poisson-Boltzmann surface area (MM-PBSA) based binding free energy estimates. The predicted Gibbs binding free energies indicate highly favorable interactions between SBL-027 and both Akt and MEK1 kinases. In vitro, SBL-027 displayed an IC50 value of 195.20nM against Akt and 239.10nM against MEK1 enzymes. The compound exhibited potent inhibition of cell proliferation in KATOIII and SNU-5 cells, with GI50 values of 490.70 and 615.14nM, respectively. Moreover, SBL-027 induced an increase in the sub G0/G1 population during the cell cycle of KATOIII and SNU-5 cells, while facilitating early and late-phase apoptosis in these cell lines. Notably, the compound significantly reduced the percentage of dual-positive cells expressing both MEK1 and Akt in gastric cancer cells. The strong binding affinity, stability, and favorable thermodynamics of SBL-027 along with the established in vitro efficacy highlight its potential as a lead compound for further preclinical and clinical development.

Advances in Pure Drug Self-Assembled Nanosystems: A Novel Strategy for Combined Cancer Therapy.

Nanoparticle-based drug delivery systems hold great promise for improving the effectiveness of anti-tumor therapies. However, their clinical translation remains hindered by several significant challenges, including intricate preparation processes, limited drug loading capacity, and concerns regarding potential toxicity. In this context, pure drug-assembled nanosystems (PDANSs) have emerged as a promising alternative, attracting extensive research interest due to their simple preparation methods, high drug loading efficiency, and suitability for large-scale industrial production. This innovative approach presents new opportunities to enhance both the safety and therapeutic efficacy of cancer treatments. This review comprehensively explores recent progress in the application of PDANSs for cancer therapy. It begins by detailing the self-assembly mechanisms and fundamental principles underlying PDANS formation. The discussion then advances to strategies for assembling single pure drug nanoparticles, as well as the co-assembly of multiple drugs. Subsequently, the review addresses the therapeutic potential of PDANSs in combination treatment modalities, encompassing diagnostic and therapeutic applications. These include combinations of chemotherapeutic agents, phototherapeutic approaches, the integration of chemotherapy with phototherapy, and the synergistic use of immunotherapy with other treatment methods. Finally, the review highlights the potential of PDANSs in advancing tumor therapy and their prospects for clinical application, providing key insights for future research aimed at optimizing this technology and broadening its utility in cancer treatment.

SNP rs9364554 Modulates Androgen Receptor Binding and Drug Response in Prostate Cancer.

(1) Background: Prostate cancer treatment efficacy is significantly influenced by androgen receptor (AR) signaling pathways. SLC22A3, a membrane transporter, has been linked to SNP rs9364554 risk loci for drug efficacy in prostate cancer. (2) Methods: We examined the location of SNP rs9364554 in the genome and utilized TCGA and other publicly available datasets to analyze the association of this SNP with SLC22A3 transcription levels. We verified onco-mining findings in prostate cancer cell lines using quantitative PCR and Western blots. Additionally, we employed electrophoretic mobility shift assay (EMSA) to detect the binding affinity of transcription factors to this SNP. The ChIP-Seq was used to analyze the enrichment of H3K27ac on the SLC22A3 promoter. (3) Results: In this study, we revealed that SNP rs9364554 resides in the SLC22A3 gene and affects its transcription. The downregulation of SLC22A3 is associated with drug resistance. More importantly, we found that this SNP has different binding affinities with transcription factors, specifically FOXA1 and AR, which significantly affects their regulation of SLC22A3 transcription. (4) Conclusions: Our findings highlight the potential of using this SNP as a biomarker for predicting chemotherapeutic outcomes and uncover possible mechanisms underlying drug resistance in advanced prostate cancers. More importantly, it provides a clinical foundation for targeting FOXA1 to enhance drug efficacy in prostate cancer patients.

Graphene/carbohydrate polymer composites as emerging hybrid materials in tumor therapy and diagnosis.

Despite the introduction of various types of treatments for cancer control, cancer therapy faces several challenges such as aggressive behavior, heterogeneous characteristics, and the development of resistance. In contrast, the methods have depended on the creation and formulation of nanoparticles to impede tumor growth. Carbon nanoparticles have attracted considerable attention for cancer therapy, with graphene nanoparticles emerging as promising vehicles for delivering drugs and genes. Moreover, graphene composites can enhance immunotherapy, phototherapy, and combination therapies. Nonetheless, the biocompatibility and toxicity of graphene composites present difficulties. Consequently, this manuscript assesses the alteration of graphene nanocomposites using carbohydrate polymers. Altering graphene composites with carbohydrate polymers such as chitosan, hyaluronic acid, cellulose, and starch can enhance their efficacy in cancer treatment. Furthermore, graphene composites functionalized with carbohydrate polymers for tumor ablation induced by phototherapy. Graphene oxide and graphene quantum dots have been modified with carbohydrate polymers to enhance their therapeutic and diagnostic uses. These nanoparticles can transport gene therapy techniques like siRNA in the treatment of cancer. Despite the breakdown of these nanoparticles within the body, they maintain excellent biosafety and biocompatibility.

Comprehensive Investigation of Proteoglycan Gene Expression in Breast Cancer: Discovery of a Unique Proteoglycan Gene Signature Linked to the Malignant Phenotype

ABSTRACTSolid tumors present a formidable challenge in oncology, necessitating innovative approaches to improve therapeutic outcomes. Proteoglycans, multifaceted molecules within the tumor microenvironment, have garnered attention due to their diverse roles in cancer progression. Their unique ability to interact with specific membrane receptors, growth factors, and cytokines provides a promising avenue for the development of recombinant proteoglycan‐based therapies that could enhance the precision and efficacy of cancer treatment. In this study, we performed a comprehensive analysis of the proteoglycan gene landscape in human breast carcinomas. Leveraging the available wealth of genomic and clinical data regarding gene expression in breast carcinoma and using a machine learning model, we identified a unique gene expression signature composed of five proteoglycans differentially modulated in the tumor tissue: Syndecan‐1 and asporin (upregulated) and decorin, PRELP and podocan (downregulated). Additional query of the breast carcinoma data revealed that serglycin, previously shown to be increased in breast carcinoma patients and mouse models and to correlate with a poor prognosis, was indeed decreased in the vast majority of breast cancer patients and its levels inversely correlated with tumor progression and invasion. This proteoglycan gene signature could provide novel diagnostic capabilities in breast cancer biology and highlights the need for further utilization of publicly available datasets for the clinical validation of preclinical experimental results.