Anticancer Therapy Research Articles

Exploring antitumor activity of novel imidazo[2,1-b]thiazole and imidazo[1,2-a]pyridine derivatives on MDA-MB-231 cell line: Targeting VEGFR-2 enzyme with computational insight

Our study explored the anticancer potential of novel heterocyclic compounds, specifically 6a-d, 8a-d, 12a-d, and 13a-d, which are derived from imidazo[2,1-b]thiazole and imidazo[1,2-a]pyridine and linked through a hydrazide moiety. These compounds were assessed for their anticancer activity toward the MDA-MB-231 breast cancer cell line to evaluate their effectiveness in inhibiting cancer cell proliferation. Among the compounds tested, 13c and 13d emerged as the most active, with IC50 values of 4.40 ± 2.87 µM and 4.69 ± 2.55 µM, respectively. These two compounds were further investigated for their effects on VEGFR-2 enzymatic activity, cell cycle progression, and apoptosis, then 13c and 13d were further evaluated for their impact on DNA fragmentation using the comet assay. Both compounds demonstrated a significant increase in DNA fragmentation, with levels of damage being twice as high as those observed in the untreated control cells. Molecular docking studies through VEGFR-2 demonstrated that compounds 13c and 13d bind to VEGFR-2 in a manner comparable to the co-crystallized ligand sunitinib I. Further analysis using density functional theory highlighted their favorable physical properties. Additionally, computational evaluations of ADME and drug-likeness suggest that these derivatives hold promise and merit further investigation. The ultimate goal is to develop effective, safe, and orally bioavailable VEGFR-2 inhibitors for potential use in anticancer therapy.

Emerging Trends in Quinoxaline‐based Analogs as Protein Kinase Inhibitors: Structural Developments and SAR Insights

Cancer remains a leading cause of mortality and has been recognized as a significant global health concern. Although numerous effective anticancer agents are available; most of the current drugs lack specificity, leading to common side‐effects associated with chemotherapy. Recent research, however, offers promise for developing more targeted and safer anticancer therapies through protein kinase inhibition. Quinoxaline derivatives represent a notable class of heterocyclic compounds. The extensive spectrum of biological activities demonstrated by quinoxalines has garnered substantial research interest. Quinoxaline and its derivatives have emerged as a novel class of chemotherapeutic agents with significant activity against various tumors through protein kinase inhibition. This review aims to elucidate recent advancements in the quinoxaline derivatives targeting protein kinase along with structural developments and structure‐activity relationships associated with these compounds.

Intralesional corticosteroid therapy for non-healing persistent radiation-induced oropharyngeal mucositis.

Oropharyngeal mucositis is a common complication of anticancer therapy. This study aimed to determine the effectiveness and safety of intralesional corticosteroid therapy (ICT) in the management of persistent mucositis. A retrospective chart review of patients who underwent ICT in the oral cavity to manage oral mucositis managed with basic oral care and preventive modalities and persisting at least 6 weeks after head and neck radiation or chemoradiation therapy completion between November 2017 and September 2023 was performed. Bio-demographic data, cancer and anticancer therapy characteristics, medical history, and mucositis-related variables were extracted from electronic medical records. Among the 34 participants, 22 (64.7%) were male. Twenty (58.8%) participants received radiotherapy; the rest received chemoradiation therapy. Before the ICT, the median mucositis lesion surface area was 225 mm2 (range 9-2025 mm2), and 22 (64.7%) patients had grade III mucositis. Post-intervention, the median size was reduced to 0 mm2 (range 0-1600 mm2). Clinically effective response (≥ 75% size and symptom reduction) was observed in 28 (82.4%) participants over a median of 26 days (7-60 days). Within this cohort, complete healing of the lesion was seen in 18 (64.3%) subjects. Overall, 25 (73.5%) participants experienced a downgradation in the mucositis stage. Local complications from injections were found in two (5.7%) participants. A correlation was found between clinically effective relief and absence of trismus (p = .03) and smaller pre-procedure surface area (p = .009). The ICT represents a viable option in managing non-healing, persistent radiation, and chemoradiation-induced oral mucositis. The modality was well tolerated and had no systemic complications.

Dysregulation of R-loop homeostasis shapes the immunosuppressive microenvironment and induces malignant progression in melanoma.

Dysregulated R-loop homeostasis leads to DNA replication stress and genomic instability, a major driver of cancer. However, the role of R-loops in melanoma development remains unclear. We established an R-loop scoring model based on a single-cell RNA sequencing dataset and evaluated the association between the R-loop score with the melanoma immune microenvironment and treatment response. We explored the role of CENPA-mediated changes in R-loop distribution during melanoma progression by DNA/RNA immunoprecipitation and sequencing and a series of functional experiments. We found that malignant cells with high R-loop scores may be involved in melanoma progression by modulating immune evasion, metabolic reprogramming, and cancer-related pathways. A cell communication analysis revealed that high-score R-loops play an important role in altering cell-cell interactions and limiting the CD8 + cytotoxic T cell response and T cell accumulation. CENPA silencing induced changes in R-loop distribution, upregulated Hippo signaling activity, and inhibited tumor cell proliferation and migration. Moreover, the R-loop score can predict the prognosis and immunotherapy effect of melanoma patients. Our work reveals the potential molecular mechanism by which abnormal R-loops promote melanoma progression, which may help develop anticancer therapies based on R-loops or R-loop regulators.

Ferroptosis meets microRNAs: a new frontier in anti-cancer therapy.

Ferroptosis is an iron-dependent lipid peroxidation-mediated cell death. It is distinct from other types of cellular death and is recognized as a potential target for cancer therapy. This review discusses the mechanisms of ferroptosis, including its induction and inhibition pathways, its role in lipid metabolism, and its connection to various signaling pathways. We also explored the relationship between microRNAs and ferroptosis, highlighting the potential role of miRNAs targeting genes involved in ferroptosis. Role of miRNAs in metabolic reprogramming during carcinogenesis is well documented. We have discussed the role of miRNAs regulating expression of genes involved in iron metabolism, lipid metabolism, and redox metabolism which are associated with regulation of ferroptosis. In conclusion, we addressed various opportunities and challenges identified in ferroptosis research and its clinical implementation stressing the necessity of customized treatment plans based on each patient's unique vulnerability to the disease. Our article provides a complete overview of microRNAs and ferroptosis, with possible implications for cancer therapy.

Understanding the Biology and Testing Techniques for Pharmacogenomics in Oncology: A Practical Guide for the Clinician.

Pharmacogenomic (PGx) testing is a growing area of personalized medicine with demonstrated clinical utility in improving patient outcomes in oncology. PGx testing of pharmacogenes affecting drug pharmacokinetics, pharmacodynamics, and response can help inform drug selection and dosing of several anticancer therapies and supportive care medications. Several PGx testing techniques exist including polymerase chain reaction (PCR), MassARRAY, microarray, and sequencing. This review article provides a clinician-friendly guide of these techniques. Understanding the advantages, limitations, ideal use, and potential clinical applications of each platform can help clinicians choose the appropriate PGx testing platform for specific use cases.

Luminescent Silver Nanoparticles Biosynthesis Using Couroupita guianensis Flower Extract: Antibacterial and Anticancer Potential

ABSTRACTGreen synthesis of nanoparticles has become a significant area of research, driven by the demand for sustainable, economical, and environmentally friendly processes, particularly in biomedical applications. In this study, silver nanoparticles (AgNPs) were produced using 10 g of Couroupita guianensis flower extract through a straightforward and environmentally friendly method. The biosynthesized AgNPs were characterized using UV–Vis spectroscopy, XRD, FTIR, SEM, and EDS techniques, confirming their successful formation and structural properties. The antibacterial efficacy of the AgNPs was assessed against Escherichia coli and Listeria monocytogenes, achieving 99.5% inactivation for E. coli and 99.3% inactivation for L. monocytogenes after 120 min of visible light exposure. Additionally, the AgNPs showed notable anticancer effects against breast cancer cells (MDA‐MB‐231), displaying a dose‐dependent decrease in cell viability, with reductions of 15%, 30%, 72%, and 86% observed at concentrations of 25, 50, 75, and 100 μg/mL, respectively. The spherical morphology of the synthesized AgNPs contributed to enhanced interactions with bacterial and cancer cells, underpinning their effectiveness. Furthermore, the mechanisms underlying these antibacterial and anticancer effects were analyzed, highlighting the unique phytochemical properties of the extract that assist in biosynthesis and activity enhancement. These findings suggest that green‐synthesized AgNPs derived from C. guianensis flower extract hold significant potential for use in biomedical applications, particularly in antibacterial and anticancer therapies.

Perceptions, Uses, and Information Sources of Medical Cannabis Among Patients with Cancer

Purpose: While medical cannabis (MC) has been shown to relieve cancer- and treatment-related symptoms, there is increasing misinformation regarding its anti-tumor efficacy. We aimed to identify opportunities for oncologists to communicate evidence-based guidance to patients regarding its use. Methods: Patients with cancer seen in radiation oncology clinic between June 2022 and July 2023 were surveyed with a questionnaire regarding their perceptions and information sources of MC. Associations between survey responses and demographic and disease variables were evaluated. Qualitative thematic analysis was performed on narrative responses in search of common themes. Results: Eighty-four patients (84% completion rate) were included in the analysis. Most (83.3%) strongly agreed or agreed that MC can provide symptom relief, while a subset of patients (15.5%) strongly agreed or agreed that MC can cure cancer. This latter subcohort was significantly more likely to identify as Hispanic/Latino (38.5% versus 9.9%, p= 0.009) and less likely to be up to date on COVID vaccinations (30.8% versus 8.5%, p= 0.044). Identifying as Hispanic/Latino remained significantly associated with strongly agreeing or agreeing that MC can cure cancer on bivariate analysis (odds ratio 6.528, 95% CI 1.477-28.715, p=0.012). Education level, other sociodemographic characteristics, and sources for information about MC were not significantly different between these patients. Thematic analysis revealed that patients hoped to learn more about MC from their oncologists but perceived them to be unknowledgeable on the subject. Conclusions: While most patients consider MC to be a valuable addition to conventional therapies for managing refractory symptoms, a subset believed it had potential as an anti-cancer therapy. Many patients rely on unregulated sources, highlighting the need for providers to address misinformation, bridge knowledge gaps, and clarify its use.

Assessing antioxidant responses in C6 and U-87 MG cell lines exposed to high copper levels

Copper excess has been tested as an anticancer therapy, due to its properties to generate oxidative stress resulting in tumoral cell death. Thus, this study aimed to evaluate the impact of copper excess on oxidative stress and antioxidant responses in glioma cells, establishing the antioxidant system as a target of copper toxicity in tumoral cells. C6 and U-87 MG cells were exposed to CuSO4 (0–600 μM) for 24-48 h. SOD, CAT, GPx, GR, and CK activities, protein and non-protein thiol levels (PSH and NPSH), and O2− production were assessed, alongside SOD1, GPx1, and GR gene expression. Results revealed a decrease in GPx, GR, and CAT activity after CuSO4 exposure in both cell lines over 24-48 h, while SOD activity initially increased, then declined after 48 h. CK activity was also decreased in C6 cells. NPSH and PSH levels dropped after 24 h, and O2− production was observed in all CuSO4 concentrations. GR mRNA was reduced in both cell lines, contrasting with increased GPx1 mRNA in C6. U-87 MG cells exhibited higher levels of SOD1 mRNA, while C6 cells displayed lower expression. Our findings suggest that copper excess limits antioxidant enzyme activity and thiol levels, particularly in the C6 cells, likely attributable to oxidative stress or direct copper-enzyme interactions. Moreover, our results imply differences in copper toxicity regarding the cell lineage used, highlighting the importance of analyzing high copper levels effects in different models. Moreover, it could be proposed that the antioxidant system is a target of copper toxicity, contributing to glioma cell death.

Widespread Adoption of Precision Anticancer Therapies After Implementation of Pathologist-Directed Comprehensive Genomic Profiling Across a Large US Health System.

Precision therapies and immunotherapies have revolutionized cancer care, with novel genomic biomarker-associated therapies being introduced into clinical practice rapidly, resulting in notable gains in patient survival. Despite this, there is significant variability in the utilization of tumor molecular profiling that spans the timing of test ordering, comprehensiveness of gene panels, and clinical decision support through therapy and trial recommendations. To standardize testing, we designed a pathologist-directed test ordering system at the time of diagnosis using a 523-gene DNA/RNA hybrid comprehensive genomic profiling (CGP) panel and extensive clinical decision support tools. To comprehensively characterize the clinical impact of this protocol, we developed a novel natural language processing (NLP)-based approach to extract clinical features from physician chart notes. We assessed test actionability rates, therapy choice, and outcomes across a set of 3,216 patients with advanced cancer. We observed 49% of patients had at least one actionable genomic biomarker-driven-approved and/or guideline-recommended targeted or immunotherapy (IO) and 53% of patients would have been eligible for a precision therapy clinical trial from three large basket trials. When assessing CGP versus an in silico 50-gene panel, 67% of tumors compared with 33% harbored actionable alterations including clinical trials. Among patients with 6 months or more of follow-up, over 52% received a targeted therapy (TT) or IO, versus 32% who received conventional chemotherapy alone. Furthermore, patients receiving TT had significantly improved overall survival compared with patients receiving chemotherapy alone (P < .001). Overall, these data represent a major shift in standard clinical practice toward molecularly guided treatments (targeted and immunotherapies) over conventional systemic chemotherapy. As guidelines continue to evolve and more precision therapeutics gain approval, we expect this gap to continue to widen.

An injectable dual-layer chitosan-alginate nano-hydrogel incorporated Cu(I)-isopolymolybdate-based metal-organic framework tailored for three-in-one anti-cancer nanotherapy

Designing potential agents and constructing hydrophilic nano-hydrogel platforms for biomedical and pharmaceutical applications, especially for polyoxometalate-based metal-organic frameworks (PMOF), present both great desirability and significant challenges. A unique open porous Cu(I)-isopolymolybdate-based metal-organic framework (CCUT) has been self-assembled through ionothermal processes for in vivo synergistic anti-cancer therapy. The periodicity of Drugs@CCUT-1 (nano-crystals of CCUT after cation exchange and anti-cancer drugs upload) has been investigated by synchrotron wide-angle X-ray scattering, confirming the lattice structure unchanged. To mitigate toxicity, enhance stimuli-responsive drug delivery, hydrophilicity, and biocompatibility, an injectable dual-layer chitosan//alginate-based nano-hydrogel is developed to incorporate Drugs@CCUT-1. Potential interactions between the chitosan layer and the surface of CCUT-1 have been analyzed by Density Functional Theory (DFT). Furthermore, the nanoparticles Drugs@CCUT-1@Gel exhibit efficient type I photodynamic therapy (PDT) and chemodynamic therapy (CDT) within the bio-window, effectively eradicating tumors in deep tissue. CCUT-1 generates a substantial amount of reactive oxygen species (ROS), stimulating the Keap1-Nrf2 signaling pathway and resulting in the expression of phase II enzymes, typically HO-1. CCUT-1@Gel not only demonstrates high capacity for anti-cancer drug upload and release, but also exhibits strong synergistic CDT/PDT in vivo anti-tumor efficacy. Hence, CCUT-1@Gel represents a promising in vivo nano-platform for synergistic chemotherapy (CT)/CDT/PDT three-in-one anti-cancer approach.

Xanthone-loaded niosomes as innovative potential delivery platform: formulation, characterization, and cytotoxic effect on human cancer cell lines

Cancer poses a perpetual threat to public health, presenting challenges in therapy due to the unregulated proliferation and intricate nature of tumors. Xanthone (Xan) exhibits anti-cancer activity, yet its therapeutic potential is hindered by its limited aqueous solubility and intestinal permeability. To address this issue, we attempted to formulate Xan into niosomes using a (21.41) full factorial design, investigating lipid amount and surfactant/stabilizer ratio impact on vesicle size (VS), entrapment efficiency percentage (EE%) and release efficacy percentage (RE%). The optimal formula was characterized for its ex-vivo permeation, morphology, and in-vitro cytotoxicity using a panel of eight human cancer cell lines. Cell cycle analysis was employed to determine the optimal formula's potential for inducing cell cycle arrest. Annexin V-FITC binding, Bax (BCL2-Associated X Protein), and Bcl-xl (B-cell lymphoma-extra-large) protein expression levels were assessed to determine the degree of apoptosis. Cell migration was assessed by the wound healing assay. The optimal formula (F1), with a desirability value of 0.924, demonstrated minimized VS (83.21±4.37 nm), maximized EE% (66.50±4.43%), and maximized RE% (77.05±1.19%). F1 exhibited enhanced ex-vivo permeation (by 4.96-fold compared to Xan suspension), and morphological integrity. F1 displayed notable antiproliferative effects, particularly in HepG2 and MCF-7 cells with IC50 values of 5.4±0.11 μM and 15.6±0.22 μM, respectively. The anticancer effect was further evidenced by its ability to inhibit cell migration, G1 phase cell cycle arrest, apoptosis induction, and increased Bax/Bcl-xl expression in HepG2 and MCF-7 cells. Accordingly, Xan-loaded niosomes exhibit encouraging potential as a potent anticancer therapy, warranting further exploration.

The Role of Fatty Acid Metabolism, the Related Potential Biomarkers, and Targeted Therapeutic Strategies in Gastrointestinal Cancers.

Gastrointestinal cancer has emerged as a significant global health concern due to its high incidence and mortality, limited effectiveness of early detection, suboptimal treatment outcomes, and poor prognosis. Metabolic reprogramming is a prominent feature of cancer, and fatty acid metabolism assumes a pivotal role in bridging glucose metabolism and lipid metabolism. Fatty acids play important roles in cellular structural composition, energy supply, signal transduction, and other lipid-related processes. Changes in the levels of fatty acid metabolite may indicate the malignant transformation of gastrointestinal cells, which have an impact on the prognosis of patients and can be used as a marker to monitor the efficacy of anticancer therapy. Therefore, targeting key enzymes involved in fatty acid metabolism, either as monotherapy or in combination with other agents, is a promising strategy for anticancer treatment. This article reviews the potential mechanisms of fatty acid metabolism disorders in the occurrence and development of gastrointestinal tumors, and summarizes the related potential biomarkers and anticancer strategies.

Jing-Si Herbal Tea attenuates oral cancer cell viability, migration, and invasion by regulating epithelial-to-mesenchymal transition and reactive oxygen species accumulation

Background/purposeOral cancer is the sixth most common cancer worldwide and can be life-threatening if not diagnosed and treated in its early stages. Jing-Si Herbal Tea (JSHT), containing eight traditional Chinese medicine-based herbs, is known to suppress the malignancy, growth, and metastasis of several tumor cells, including breast, lung, and colon cancer cells. However, the pharmacological effect of JSHT on oral cancer progression is still unclear. Materials and methodsIn this study, we evaluated the potential of JSHT to arrest the development of oral cancer via induction of cell death by reactive oxygen species (ROS) accumulation and inhibition of migration, invasion, and epithelial-to-mesenchymal transition (EMT). For this purpose, we employed the human tongue squamous cell carcinoma SAS cell line, which we treated with different JSHT concentrations for 24 h, and assessed cell viability, migration, and wound healing capabilities, together with western blotting for measuring expression levels of EMT markers. ResultsSurvival, migration/invasion ability, EMT, and ROS production in the SAS human tongue squamous carcinoma and FaDu human pharynx squamous cell carcinoma cell line were decreased by JSHT treatment via Lon protease-independent mechanisms. ConclusionThis study demonstrates that JSHT could be regarded as a candidate new supplement to existing anticancer therapies and an alternative, orally administered healthcare product for treating oral squamous cell carcinoma.

Synthesis, characterization and anticancer activity of zinc sulfide nanoparticle using heterocyclic Zn (II) thiosemicarbazone complex as a single source

The green synthesis of zinc sulphide nanoparticles (Zn S NPs) using Zn(II) complex as a single molecular precursor is gaining importance due to its simplicity, cost – effectiveness and pharmacologically active nature. Now – a- day’s nanobiotechnolgy is increasing at a fast rate due to its many possible applications in the biomedical and, pharmaceuticals fields. In this paper, we have reported the synthesis of Chalcogenide nanostructured pharmacologically active Zn S nanoparticles using Zn (II) Heterocyclic thiosemicarbazone Complex as a Single Source. Zn (II) complex was synthesized by the reaction between Schiff base ligand and Zinc acetate salt in 2:1 molar ratio. Thiosemicarbazone have a wide clinical antitumor spectrum with efficacy in various tumor types such as leukemia, pancreatic cancer, breast cancer, non- small cell lung cancer, cervical cancer, prostate cancer and bladder cancer. These compounds possessed significant antineoplastic activity when the carbonyl group attachment of the side chain was located at a position alpha to the heterocyclic nitrogen atom, whereas attachment of the side chain ꞵ or gamma to the heterocyclic nitrogen atom, resulted in inactive antitumor agents. In addition, replacement of the heterocyclic ring N with carbon also resulted in a biologically inactive compound suggesting that a conjugated N, N, S -tridentate donor set is essential for the biological activities of thiosemicarbazone ligands. In our study, for synthesis of Zn S nanoparticles, the synthesized Zn(II) complex of thiosemicarbazone ligand was treated with aqueous extract of Parmotrema perlatum flowers. The use of aqueous extract of Parmotrema perlatum flowers in the synthesis of ZnS particles plays a very important role in reducing reaction time, reducing minimum possibility of side reactions and conversion of metal complexes into its nanoparticles in a very less time. All synthesized compounds were characterized by various structural, morphological, electronic and vibrational spectroscopic techniques and also evaluate the pharmacological activities of compounds like antioxidant, anti-inflammatory and anticancer activities. The peaks at 3414.82 cm-1 in FT-IR spectra confirms the presence of –OH groups and other bioactive agents in the aqueous extract of Parmotrema perlatum flowers, which acts as a capping and stabilizing agents in the synthesis of Zn S nano particles. The effective results of anti-cancer activity of compounds showed that the ZnS nanoparticles shows good cytotoxic activity against human breast cancer cell lines (MCF-7) using MTT assay. In this study, normal human cell lines used as standard for comparison purpose. The CTC50 values of ZnS nanoparticles was found to be 49.375µg/ml respectively. Therefore, it could be concluded that this biogenic method is effective for synthesis of Zn S nanoparticles from Zn(II) complex with desirable properties for potential biomedical applications which can be consider as a good drug candidate for anti-cancer therapy

MAIN WAYS OF THE INITIATION OF CANCER CELL DORMANCY: TGFβ ROLE

The development of metastases even long after treatment is one of the most important problems of medicine. There are mechanisms helping cancer cells to survive at various steps of metastasis. The ability of cancer cells to turn into dormant state characterizing of reversible cell cycle blockage is one of such mechanisms. Dormancy is regulated by many factors including TGFβ. The aim of the review to summarize the information about the mechanisms of dormancy development in primary and secondary sites as well as about the role of TGFβ in cancer cell phenotype regulation and its cooperation with intra- and extracellular factors are supposed to promote dormancy development Material and methods. The materials are the results of the investigations on the theme of russian and foreign researchers and ours published data over the past 9 years, from 2015 till 2024. Results. Modern data about the roles of the factors produced by primary tumor and target organ cells in dormancy development are summarized in the article. Dormant phenotype induction can be initiated not only in primary tumor under the influence of hypoxia, pH alterations, inflammation and immune cells regulation etc., but also in the sites of metastasis as a result of the influence of factors produced by primary tumor as well as target organ cells. Modern data allow to suppose, that TGFβ influencing a number of complicated processes can prevent dormancy development and promote cancer cells to reenter cell cycle. Conclusion. Further investigation in this field allow a deeper understanding of the mechanisms of the TGFβ influence on dormant cells and will promote the creation of new strategies of anticancer therapy on the basis of TGFβ activity modulation

Exploring the Therapeutic Potential of Ginkgo biloba Polyphenols in Targeting Biomarkers of Colorectal Cancer: An In-silico Evaluation.

Colorectal cancer (CRC) is a major contributor to cancer-related deaths worldwide, driving the need for effective anticancer therapies with fewer side effects. The exploration of Ginkgo biloba, a natural source, offers a hopeful avenue for novel treatments targeting key colorectal biomarkers involved in CRC treatment. The aim of this study was to explore the binding affinity of natural molecules derived from G. biloba to essential biomarkers associated with CRC, including Kirsten rat sarcoma virus, neuroblastoma RAS mutations, serine/threonine-protein kinase B-Raf, phosphatidylinositol 3'-kinase, and deleted colorectal cancer, using molecular docking. The focus of this research was to evaluate how effectively these molecules bind to specified targets in order to identify potential inhibitors for the treatment of CRC. A total of 152 polyphenolic compounds from G. biloba were selected and subjected to molecular docking simulations to evaluate their interactions with CRC-related biomarkers. The docking results were analysed to identify ligands exhibiting strong affinities towards the targeted genes, suggesting potential inhibitory effects. Docking simulations unveiled the strong binding affinities between selected polyphenolic compounds derived from G. biloba and genes associated with CRC. The complex glycoside structures that are found in flavonols are of significant importance. These compounds, including derivatives with distinctive arrangements, exhibited promising docking scores, signifying substantial interactions with the targeted biomarkers. The study demonstrates the potential of G. biloba-derived molecules as effective anticancer agents for colorectal cancer. The identified ligands exhibit strong interactions with crucial CRC-related biomarkers, suggesting potential inhibition ability. Further in vitro and in vivo investigations are needed to validate and build upon these promising findings, advancing the development of novel and efficient CRC therapies.

The impact of the COVID-19 pandemic on the dispensing of systemic anti-cancer therapy (SACT) in Ireland: a population based study

ObjectivesThe COVID-19 pandemic had considerable implications for cancer related care. This study aimed to examine its impact on the dispensing of systemic anti-cancer therapy (SACT) in Ireland. Study designA repeated cross-sectional design was used which involved a quasi-experimental interrupted time series analysis (ITSA), and autoregressive integrated moving average (ARIMA) models. MethodsThis nationally representative study utilised monthly pharmacy claims (i.e. dispensing) data from community and hospital schemes. Dispensed items among individuals prescribed any SACT from January 2019 to April 2021 were included. ResultsDuring the study period, 641,273 SACT items were dispensed, including 57,199 chemotherapeutic agents (8.9%), 15,970 immunotherapeutic agents (2.5%), 87,813 targeted therapies (13.7%), and 480,291 (74.9%) endocrine therapies. There were on average 3.3 and 4.1 fewer immunotherapy and targeted therapy agents, respectively, dispensed per 100,000 population per month post-March 2020 (vs. expected), compared to the level prior to March 2020. For endocrine therapy, there was a significant slowing of the trend post-March 2020 compared to the pre-pandemic period (slope change = -1.72, 95% CI -2.9 to -0.5; p<0.01). ConclusionThere was a significant level decrease in the dispensing of immunotherapy and targeted therapy during the first year of the pandemic, and a slowing of the trend for endocrine therapies. However, no differences in the dispensing of other SACT were observed.

Role of relaxin signaling in Cancer: A review.

The investigation into relaxin (RLN), additional RLN-like proteins, and RLN family peptide receptors (RXFP) has demonstrated their role in modulating the extracellular matrix (ECM), immune cells, specifically macrophages, and angiogenesis, with recent evidence showing an effect on signaling pathways in tumor cells. These findings serve as the basis for our narrative review to collate pertinent studies in this field and provide our perspective on their clinical and investigational significance. In the article, we discuss findings from pertinent studies focusing on evaluating the expression or effect of RLN1, RLN2, or RXFP1 in various cancers. We also briefly discuss the potential role that other RLN family peptides and their receptors play in cancer. Specifically, we delve into questions regarding RLN signaling in terms of parity/pregnancy-associated protection from mammary tumors, expression in tumors, detection in serum in the setting of cancers, effect on tumor-adjacent cells, effect on tumorigenesis depending on endogenous expression or delivery, and last, but not the least, impact on the effectiveness of anti-cancer therapies. We expect that summarizing the available literature to answer these questions will allow readers to understand the role of RLN-receptor interaction in cancer as well as identify areas of uncertainty and avenues for future investigation.

Progresses and Pitfalls of Epigenetics in Solid Tumors Clinical Trials.

Epigenetic dysregulation has long been recognized as a significant contributor to tumorigenesis and tumor maintenance, impacting all recognized cancer hallmarks. Although some epigenetic drugs have received regulatory approval for certain hematological malignancies, their efficacy in treating solid tumors has so far been largely disappointing. However, recent advancements in developing new compounds and a deeper understanding of cancer biology have led to success in specific solid tumor subtypes through precision medicine approaches. Moreover, epigenetic drugs may play a crucial role in synergizing with other anticancer treatments, enhancing the sensitivity of cancer cells to various anticancer therapies, including chemotherapy, radiation therapy, hormone therapy, targeted therapy, and immunotherapy. In this review, we critically evaluate the evolution of epigenetic drugs, tracing their development from initial use as monotherapies to their current application in combination therapies. We explore the preclinical rationale, completed clinical studies, and ongoing clinical trials. Finally, we discuss trial design strategies and drug scheduling to optimize the development of possible combination therapies.