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Chemotherapy-induced peripheral neuropathy (CIPN) affects a significant majority of cancer patients, with up to 80% experiencing this severe and dose-limiting side effect while undergoing anti-cancer treatment. CIPN can be induced by a variety of drugs commonly employed in the management of both solid tumors and hematologic cancers. The inadequacies in comprehending the pharmacological interventions associated with CIPN and the subsequent signaling pathways have significantly contributed to the disappointing outcomes of several drugs in clinical trials. Recent investigations in pain research have demonstrated a growing inclination toward addressing neuro-inflammation as a strategy for managing chronic pain conditions. Notably, toll-like receptor-4 (TLR-4) has emerged as a key player in immune system activation and is undergoing extensive research. In this review, we emphasize the potential role of TLR-4 in neuropathic pain, highlighting its promise as a target for CIPN treatment. Furthermore, we explore and analyse the intricate interplay between TLR-4, diverse immune cells, downstream pathways, and receptors within the context of CIPN. A comprehensive exploration of these interactions provides valuable insights into the central role of TLR-4 in CIPN development, paving the way for potential ground-breaking therapeutic approaches to alleviate this debilitating condition. [ABSTRACT FROM AUTHOR]

Background: The release of extracellular vesicles (EVs) including exosomes from human mesenchymal stroma/stem-like cells (MSC) represents valuable cell-free carriers for the delivery of regenerative and medicinal compounds. Methods: EVs/exosomes were isolated by differential centrifugation from four individual MSC as controls and after treatment with a sub-lethal concentration of 10 mM taxol for 24 h, respectively. The isolated EVs/exosomes were characterized and quantified by nano-tracking-analysis and by Western blots. MicroRNAs (miRs) were isolated from the different EVs/exosome populations and expression levels were quantified by qPCR using 1246 miR templates. Cytotoxic effects of the different MSC-derived taxol-loaded EVs/exosomes were determined in five different GFP-transduced cancer cell lines and quantified by a fluoroscan assay with a GFP-detecting fluorimeter. The presence of stroma cell-derived factor 1 (SDF-1) in MSC-derived EVs/exosomes and its enhanced expression in the vesicles after taxol treatment of MSC was quantified by a specific ELISA. Results: EVs/exosomes isolated from four individual taxol-treated MSC displayed a larger size and higher yields as the control EVs/exosomes and were used as anti-tumor therapeutic vehicles. Application of each of the four MSC-derived taxol-loaded EVs/exosome populations revealed significant cytotoxic effects in cell lines of five different tumor entities (carcinomas of lung, breast, ovar, colon, astrocytoma) in a concentration-dependent manner. Expression analysis of 1246 miRs in these taxol-loaded EVs/exosomes as compared to the corresponding MSC-derived control EVs/exosomes unraveled a taxol-mediated up-regulation of 11 miRs with predominantly anti-tumorigenic properties. Moreover, various constitutively expressed protein levels were unanimously altered in the MSC cultures. Taxol treatment of the different MSC revealed an up-regulation of tetraspanins and a 2.2-fold to 5.4-fold increased expression of SDF-1 among others. Treatment of cancer cells with MSC-derived taxol-loaded EVs/exosomes in the presence of a neutralizing SDF-1 antibody significantly abolished the cytotoxic effects between 20.3% and 27%. Conclusions: These findings suggested a taxol-mediated increase of anti-cancer properties in MSC that enhance the tropism of derived EVs/exosomes to tumors, thereby specifically focusing the therapeutic effects of the delivered products. [ABSTRACT FROM AUTHOR]

Ral-binding/interacting protein (RLIP) acts as a transporter that responds to stress and provides protection, specifically against glutathione–electrophile conjugates and xenobiotic toxins. Its increased presence in malignant cells, especially in cancer, emphasizes its crucial antiapoptotic function. This is achieved by selectively regulating the cellular levels of proapoptotic oxidized lipid byproducts. Suppressing the progression of tumors in human xenografts can be achieved by effectively inhibiting RLIP, a transporter in the mercapturic acid pathway, without involving chemotherapy. Utilizing ovarian cancer (OC) cell lines (MDAH2774, OVCAR4, and OVCAR8), we observed that agents targeting RLIP, such as RLIP antisense and RLIP antibodies, not only substantially impeded the viability of OC cells but also remarkably increased their sensitivity to carboplatin. To delve further into the cytotoxic synergy between RLIP antisense, RLIP antibodies, and carboplatin, we conducted investigations in both cell culture and xenografts of OC cells. The outcomes revealed that RLIP depletion via phosphorothioate antisense led to rapid and sustained remissions in established subcutaneous human ovary xenografts. Furthermore, RLIP inhibition by RLIP antibodies exhibited comparable efficacy to antisense and enhanced the effectiveness of carboplatin in MDAH2774 OC xenografts. These investigations underscore RLIP as a central carrier crucial for supporting the survival of cancer cells, positioning it as a suitable focus for cancer treatment. [ABSTRACT FROM AUTHOR]

One of the most extensively used herbal medicines is chrysin, a naturally occurring flavone commonly detected in several natural products, including propolis and honey. Due to its various biological properties, such as antioxidant, anti-estrogenic, anti-inflammatory, anti-allergic, antibacterial and anticancer activities, chrysin has emerged as the leading contender for health benefits. Amongst the several pharmacological effects exhibited by chrysin, its anticancer activity is the most attractive. Several studies have demonstrated that chrysin suppresses tumor progression in cell lines and animal models by inducing apoptosis, disrupting the cell cycle and inhibiting migration without generating toxicity or undesired side-effects in normal cells. Furthermore, chrysin also inhibits multi-drug resistant proteins and is effective in combination therapy. The present review comprehensively discusses the research developments in the understanding of the potential of chrysin as a potent anticancer agent achieved by modulating various cell targets and signaling pathways involved in inflammation, cell survival, apoptosis, growth, angiogenesis, invasion and metastasis. [ABSTRACT FROM AUTHOR]

Abstract Background The release of extracellular vesicles (EVs) including exosomes from human mesenchymal stroma/stem-like cells (MSC) represents valuable cell-free carriers for the delivery of regenerative and medicinal compounds. Methods EVs/exosomes were isolated by differential centrifugation from four individual MSC as controls and after treatment with a sub-lethal concentration of 10 mM taxol for 24 h, respectively. The isolated EVs/exosomes were characterized and quantified by nano-tracking-analysis and by Western blots. MicroRNAs (miRs) were isolated from the different EVs/exosome populations and expression levels were quantified by qPCR using 1246 miR templates. Cytotoxic effects of the different MSC-derived taxol-loaded EVs/exosomes were determined in five different GFP-transduced cancer cell lines and quantified by a fluoroscan assay with a GFP-detecting fluorimeter. The presence of stroma cell-derived factor 1 (SDF-1) in MSC-derived EVs/exosomes and its enhanced expression in the vesicles after taxol treatment of MSC was quantified by a specific ELISA. Results EVs/exosomes isolated from four individual taxol-treated MSC displayed a larger size and higher yields as the control EVs/exosomes and were used as anti-tumor therapeutic vehicles. Application of each of the four MSC-derived taxol-loaded EVs/exosome populations revealed significant cytotoxic effects in cell lines of five different tumor entities (carcinomas of lung, breast, ovar, colon, astrocytoma) in a concentration-dependent manner. Expression analysis of 1246 miRs in these taxol-loaded EVs/exosomes as compared to the corresponding MSC-derived control EVs/exosomes unraveled a taxol-mediated up-regulation of 11 miRs with predominantly anti-tumorigenic properties. Moreover, various constitutively expressed protein levels were unanimously altered in the MSC cultures. Taxol treatment of the different MSC revealed an up-regulation of tetraspanins and a 2.2-fold to 5.4-fold increased expression of SDF-1 among others. Treatment of cancer cells with MSC-derived taxol-loaded EVs/exosomes in the presence of a neutralizing SDF-1 antibody significantly abolished the cytotoxic effects between 20.3% and 27%. Conclusions These findings suggested a taxol-mediated increase of anti-cancer properties in MSC that enhance the tropism of derived EVs/exosomes to tumors, thereby specifically focusing the therapeutic effects of the delivered products.

ADCs represent a transformative class of medicine that combines the specificity of monoclonal antibodies with the potency of highly cytotoxic agents through linkers, aiming to enhance the therapeutic index of cytotoxic drugs. Given the complex molecular structures of ADCs, combining the molecular characteristics of small-molecule drugs and those of large-molecule biotherapeutics, there are several unique considerations when designing nonclinical-to-clinical PK/PD translation strategies. This complexity also demands a thorough understanding of the ADC's components – antibody, linker, and payload – to the overall toxicological, PK/PD, and efficacy profile. ADC development is a multidisciplinary endeavour requiring a strategic integration of nonclinical safety, pharmacology, and PK/PD modelling to translate from bench to bedside successfully. The ADC development underscores the necessity for a robust scientific foundation, leveraging advanced analytical and modelling tools to predict human responses and optimise therapeutic outcomes. This review aims to provide an ADC translational PK/PD framework by discussing unique aspects of ADC nonclinical to clinical PK translation, starting dose determination, and leveraging PK/PD modelling for human efficacious dose prediction and potential safety mitigation. [ABSTRACT FROM AUTHOR]

The next generation of anticancer agents are emerging from rationally designed nanostructured materials. This work involved the synthesis and characterization of novel hollow DNA‐conjugated gold nanoparticles (DNA−AuNPs) for controlled drug delivery. Polyethyleneimine (PEI) was bound to AuNPs, forming polymer‐shell nanoparticles. Dissolution of the gold core via iodine formed hollow core polymeric nanoparticles (HCPNPs) and a high density (85 molecules/particle) of DNA intercalated with daunorubicin was conjugated. Particles were spherical with an average diameter of 105.7±17.3 nm and zeta potential of 20.4±3.54 mV. We hypothesize the DNA backbone electrostatically condensed to the primary amines on the surface of the particle toroidally, weaving itself within the polymer shell. During the DNA intercalation process, increasing the ionic concentration and decreasing the amine/phosphate ratio 10‐fold increased drug intercalation 64 % and 61 %, respectively, allowing us to determine the optimal method of particle synthesis. As intercalation sites increased with increasing DNA strand length, drug loading increased. An average of 874±40.1 daunorubicin molecules were loaded per HCPNP. HCPNPs with drug intercalated DNA have strong potential to be clinically efficacious drug delivery vehicles due to the versatility of DNA and high drug loading capacities. [ABSTRACT FROM AUTHOR]

Implantable drug delivery systems formed upon injection offer a host of advantages, including localized drug administration, sustained release, minimized side effects, and enhanced patient compliance. Among the various techniques utilized for the development of in situ forming drug implants, solvent-induced phase inversion emerges as a particularly promising approach. However, synthetic polymer-based implants have been associated with undesirable effects arising from polymer degradation. In response to this challenge, a novel category of drug delivery systems, known as phospholipids-based phase separation gels (PPSGs), has emerged. These gels, characterized by their low initial viscosity, exhibit injectability and undergo rapid transformation into in situ implants when exposed to an aqueous environment. A typical PPSG formulation comprises biodegradable components, such as phospholipids, pharmaceutical oil, and a minimal amount of ethanol. The minimized organic solvents in the composition show good biocompatibility. And the relatively simple composition holds promise for industrial-scale manufacturing. This comprehensive review provides an overview of the principles and advancements in PPSG systems, with specific emphasis on their suitability as drug delivery systems for a wide range of active pharmaceutical ingredients (APIs), spanning from small molecules to peptides and proteins. Additionally, we explore the critical parameters and underlying principles governing the formulation of PPSG-based drug delivery strategies, offering valuable insights on optimization strategies. [ABSTRACT FROM AUTHOR]

Despite progress in cancer treatments, it remains a leading cause of death worldwide. Current chemotherapy is often hampered by side effects, tissue damage, and drug resistance. To overcome these limitations, research is exploring new approaches to improve chemotherapy efficacy and reduce its side effects. A promising strategy involves combining chemotherapeutic drugs with phytochemicals, which are active compounds derived from plants. Nanotechnology plays a crucial role in delivering these often‐hydrophobic drugs, enhancing their bioavailability and solubility. This research area represents a significant convergence of nanotechnology with both conventional pharmaceuticals and botanical compounds. Global studies are increasingly demonstrating the potential of these combination therapies to inhibit cancer cell growth in laboratory and preclinical models. These studies suggest synergistic or additive effects that lead to improved treatment outcomes. This article focuses on recent advancements in nano‐drug delivery systems, specifically those designed for the simultaneous delivery of chemotherapeutic drugs and phytochemicals. It explores the selection of phytochemicals based on their anticancer properties, outlines the design considerations for nanocarriers, and discusses how physicochemical characteristics influence drug release kinetics. Additionally, the review examines nanoformulations that integrate synthetic drugs with natural components, highlighting the potential of herbal oils and medicines in cancer treatment. [ABSTRACT FROM AUTHOR]

Background: Vulvar squamous cell carcinoma (VSCC) is a rare disease with a poor prognosis. To date, there's no proper in vitro modeling system for VSCC to study its pathogenesis or for drug evaluation. Methods: We established healthy vulvar (HV)- and VSCC-like 3D full thickness models (FTMs) to observe the tumor-stroma interaction and their applicability for chemotherapeutic efficacy examination. VSCC-FTMs were developed by seeding VSCC tumor cell lines (A431 and HTB117) onto dermal matrices harboring two NF subtypes namely papillary fibroblasts (PFs) and reticular fibroblasts (RFs), or cancer-associated fibroblasts (CAFs) while HV-FTMs were constructed with primary keratinocytes and fibroblasts isolated from HV tissues. Results: HV-FTMs highly resembled HV tissues in terms of epidermal morphogenesis, basement membrane formation and collagen deposition. When the dermal compartment shifted from PFs to RFs or CAFs in VSCC-FTMs, tumor cells demonstrated more proliferation, EMT induction and stemness. In contrast to PFs, RFs started to lose their phenotype and express robust CAF-markers α-SMA and COL11A1 under tumor cell signaling induction, indicating a favored 'RF-to-CAF' transition in VSCC tumor microenvironment (TME). Additionally, chemotherapeutic treatment with carboplatin and paclitaxel resulted in a significant reduction in tumor-load and invasion in VSCC-FTMs. Conclusion: We successfully developed in vitro 3D vulvar models mimicking both healthy and tumorous conditions which serve as a promising tool for vulvar drug screening programs. Moreover, healthy fibroblasts demonstrate heterogeneity in terms of CAF-activation in VSCC TME which brings insights in the future development of novel CAF-based therapeutic strategies in VSCC. [ABSTRACT FROM AUTHOR]

Despite recent advancements in the diagnosis and treatment of breast cancer (BC), patient outcomes in terms of survival, recurrence, and disease progression remain suboptimal. A significant factor contributing to these challenges is the cellular heterogeneity within BC, particularly the presence of breast cancer stem cells (BCSCs). These cells are thought to serve as the clonogenic nexus for new tumor growth, owing to their hierarchical organization within the tumor. This descriptive review focuses on the evolving strategies to target BCSCs, which have become a pivotal aspect of therapeutic development. We explore a variety of approaches, including targeting specific tumor surface markers (CD133 and CD44), transporters, heat shock proteins, and critical signaling pathways like Notch, Akt, Hedgehog, KLF4, and Wnt/β-catenin. Additionally, we discuss the modulation of the tumor microenvironment through the CXCR-12/CXCR4 axis, manipulation of pH levels, and targeting hypoxia-inducible factors, vascular endothelial growth factor, and CXCR1/2 receptors. Further, this review focuses on the roles of microRNA expression, strategies to induce apoptosis and differentiation in BCSCs, dietary interventions, dendritic cell vaccination, oncolytic viruses, nanotechnology, immunotherapy, and gene therapy. We particularly focused on studies reporting identification of BCSCs, their unique properties and the efficacy of various therapeutic modalities in targeting these cells. By dissecting these approaches, we aim to provide insights into the complex landscape of BC treatment and the potential pathways for improving patient outcomes through targeted BCSC therapies. [ABSTRACT FROM AUTHOR]

Melanoma, an invasive class of skin cancer, originates from mutations in melanocytes, the pigment‐producing cells. Globally, approximately 132,000 new cases are reported each year, and in South Africa, the incidence stands at 2.7 per 100,000 people, signifying a worrisome surge in melanoma rates. Therefore, there is a need to explore treatment modalities that will target melanoma's signalling pathways. Melanoma metastasis is aided by ligand activity of transforming growth factor‐beta 1 (TGF‐β1), vascular endothelial growth factor‐C (VEGF‐C) and C‐X‐C chemokine ligand 12 (CXCL12) which bind to their receptors and promote tumour cell survival, lymphangiogenesis and chemotaxis. (3‐(4‐dimethylaminonaphthelen‐1‐ylmethylene)‐1,3‐dihydroindol‐2‐one) MAZ‐51 is an indolinone‐based molecule that inhibits VEGF‐C induced phosphorylation of vascular endothelial growth factor receptor 3 (VEGFR‐3). Despite the successful use of conventional cancer therapies, patients endure adverse side effects and cancer drug resistance. Moreover, conventional therapies are toxic to the environment and caregivers. The use of medicinal plants and their phytochemical constituents in cancer treatment strategies has become more widespread because of the rise in drug resistance and the development of unfavourable side effects. Zingerone, a phytochemical derived from ginger exhibits various pharmacological properties positioning it as a promising candidate for cancer treatment. This review provides an overview of melanoma biology and the intracellular signalling pathways promoting cell survival, proliferation and adhesion. There is a need to align health and environmental objectives within sustainable development goals 3 (good health and well‐being), 13 (climate action) and 15 (life on land) to promote early detection of skin cancer, enhance sun‐safe practices, mitigation of environmental factors and advancing the preservation of biodiversity, including medicinal plants. Thus, this review discusses the impact of cytostatic cancer drugs on patients and the environment and examines the potential use of phytochemicals as adjuvant therapy. Significance statement: Cytostatic drugs, despite being effective treatment agents, induce nontarget effects harming noncancerous cells.This review highlights the use of phytochemicals as adjuvant therapy in cancer treatment to combat the nontarget effects of cytostatic drugs.Additionally, phytochemicals as adjuvants decrease the environmental burden incurred by cytostatic drugs, promoting environmental sustainability. [ABSTRACT FROM AUTHOR]

BackgroundDrug hypersensitivity reactions (DHRs) have a significant impact on both, patient and their treating physicians; it is considered a public health concern. The history of allergy to drugs, limits therapeutic options and will lead to the use of more expensive and potentially less effective options. Drug desensitization (DD) is considered as a procedure with a positive impact on the prognosis of the patient's disease. The objective of this study is to describe the experience with a substantial number of drugs desensitization in a fourth level center in Cali, Colombia.MethodsAn observational, cross-sectional and descriptive study was conducted. Patients with DHRs who underwent a standardized institutional DD protocol, between March of 2012 and May of 2023, were included.ResultsTwo hundred forty-one patients were included. The median age was 47.8 years (4–88). One hundred fifty-six (64.7%) were women, including three who were pregnant. A total of 641 DDs were performed. The most frequent groups of drugs for which the desensitization was performed were monoclonal antibodies in 83 patients (34.4%), chemotherapeutic agents in 53 (21.6%), NSAIDs in 44 (18.2%), and antibiotics in 42 (17.4%). Eighty-seven patients (36.1%) experienced hypersensitivity to the culprit drug on first exposure, while 154 (63.9%) exhibited reactions during subsequent cycles. The main clinical presentation that gave rise to desensitization was anaphylaxis in 125 patients (51.8%), followed by cutaneous symptoms in 106 patients (44%). The predominant observed endophenotype was type 1 in 188 patients (78.3%), followed by mixed type in 46 patients (19.2%). Breakthrough reactions were observed in 50 patients (20.7%). Tolerance to DD was achieved in 636 of the procedures (99.2%), allowing the continuity of treatment of choice for the underlying disease.ConclusionsMost desensitized patients were women with type I reactions. Monoclonal antibodies were the most frequent culprit drugs. DD in patients with DHRs is a useful, safe and effective procedure. The administration of the implicated drug had a positive impact on the course of the disease in these patients.

Abstract Chemoresistance and severe toxicities represent major drawbacks of chemotherapy. Natural extracts, including the essential oils of Pistacia lentiscus (PLEO), exhibit substantial anticancer and anti-inflammatory activities where different cancers are reported to dramatically recess following targeting with PLEO. PLEO has promising antimicrobial, anticancer, and anti-inflammatory properties. However, the therapeutic properties of PLEO are restricted by limited stability, bioavailability, and targeting ability. PLEO nanoformulation can maximize their physicochemical and therapeutic properties, overcoming their shortcomings. Hence, PLEO was extracted and its chemical composition was determined by GC–MS. PLEO and 5-Fluorouracil (5FU) were electrospun into poly-ε-caprolactone nanofibers (PCL-NFs), of 290.71 nm to 680.95 nm diameter, to investigate their anticancer and potential synergistic activities against triple-negative breast cancer cells (MDA-MB-231), human adenocarcinoma breast cancer cells (MCF-7), and human skin melanoma cell line (A375). The prepared nanofibers (NFs) showed enhanced thermal stability and remarkable physical integrity and tensile strength. Biodegradability studies showed prolonged stability over 42 days, supporting the NFs use as a localized therapy of breast tissues (postmastectomy) or melanoma. Release studies revealed sustainable release behaviors over 168 h, with higher released amounts of 5FU and PLEO at pH 5.4, indicating higher targeting abilities towards cancer tissues. NFs loaded with PLEO showed strong antioxidant properties. Finally, NFs loaded with either PLEO or 5FU depicted greater anticancer activities compared to free compounds. The highest anticancer activities were observed with NFs co-loaded with PLEO and 5FU. The developed 5FU-PLEO-PCL-NFs hold potential as a local treatment of breast cancer tissues (post-mastectomy) and melanoma to minimize their possible recurrence. Graphical Abstract

Chemoresistance and severe toxicities represent major drawbacks of chemotherapy. Natural extracts, including the essential oils of Pistacia lentiscus (PLEO), exhibit substantial anticancer and anti-inflammatory activities where different cancers are reported to dramatically recess following targeting with PLEO. PLEO has promising antimicrobial, anticancer, and anti-inflammatory properties. However, the therapeutic properties of PLEO are restricted by limited stability, bioavailability, and targeting ability. PLEO nanoformulation can maximize their physicochemical and therapeutic properties, overcoming their shortcomings. Hence, PLEO was extracted and its chemical composition was determined by GC–MS. PLEO and 5-Fluorouracil (5FU) were electrospun into poly-ε-caprolactone nanofibers (PCL-NFs), of 290.71 nm to 680.95 nm diameter, to investigate their anticancer and potential synergistic activities against triple-negative breast cancer cells (MDA-MB-231), human adenocarcinoma breast cancer cells (MCF-7), and human skin melanoma cell line (A375). The prepared nanofibers (NFs) showed enhanced thermal stability and remarkable physical integrity and tensile strength. Biodegradability studies showed prolonged stability over 42 days, supporting the NFs use as a localized therapy of breast tissues (postmastectomy) or melanoma. Release studies revealed sustainable release behaviors over 168 h, with higher released amounts of 5FU and PLEO at pH 5.4, indicating higher targeting abilities towards cancer tissues. NFs loaded with PLEO showed strong antioxidant properties. Finally, NFs loaded with either PLEO or 5FU depicted greater anticancer activities compared to free compounds. The highest anticancer activities were observed with NFs co-loaded with PLEO and 5FU. The developed 5FU-PLEO-PCL-NFs hold potential as a local treatment of breast cancer tissues (post-mastectomy) and melanoma to minimize their possible recurrence. [ABSTRACT FROM AUTHOR]

Cancer is defined as the uncontrolled proliferation of heterogeneous cell cultures in the body that develop abnormalities and mutations, leading to their resistance to many forms of treatment. Left untreated, these abnormal cell growths can lead to detrimental and even fatal complications for patients. Radiation therapy is involved in around 50% of cancer treatment workflows; however, it presents significant recurrence rates and normal tissue toxicity, given the inevitable deposition of the dose to the surrounding healthy tissue. Chemotherapy is another treatment modality with excessive normal tissue toxicity that significantly affects patients' quality of life. To improve the therapeutic efficacy of radiotherapy and chemotherapy, multiple conjunctive modalities have been proposed, which include the targeting of components of the tumour microenvironment inhibiting tumour spread and anti-therapeutic pathways, increasing the oxygen content within the tumour to revert the hypoxic nature of the malignancy, improving the local dose deposition with metal nanoparticles, and the restriction of the cell cycle within radiosensitive phases. The tumour microenvironment is largely responsible for inhibiting nanoparticle capture within the tumour itself and improving resistance to various forms of cancer therapy. In this review, we discuss the current literature surrounding the administration of molecular and nanoparticle therapeutics, their pharmacokinetics, and contrasting mechanisms of action. The review aims to demonstrate the advancements in the field of conjugated nanomaterials and radiotherapeutics targeting, inhibiting, or bypassing the tumour microenvironment to promote further research that can improve treatment outcomes and toxicity rates. [ABSTRACT FROM AUTHOR]

Background: The role of CIA‐II has been clarified in several types of tumors; however, whether dysregulated CIA‐II expression is also involved in the pathophysiology of lower‐grade glioma (LGG) remains undisclosed. Methods: A comprehensive pan‐cancer analysis of the expression patterns and prognostic significance of CIA‐II in miscellaneous tumors was undertaken. Subsequently, a detailed bioinformatics analysis was executed to identify putative correlations between CIA‐II expression and clinical features, prognosis, biological functions, immunological characteristics, genomic alterations, and chemotherapeutics in LGG. In vitro studies were implemented to examine the potential roles of CIA‐II in LGG. Results: CIA‐II expression was found to be abnormally elevated in a variety of tumors, including LGG. Additionally, patients with LGG with higher CIA‐II expression owned worse prognosis. Importantly, the results declared that CIA‐II expression was an independent prognostic indicator for LGG. Moreover, the expression of CIA‐II was tightly interrelated with immune cell infiltration, gene mutations, and chemotherapeutics in LGG. In vitro studies revealed that CIA‐II was increased and strongly related to the cell proliferation in LGG. Conclusion: CIA‐II may be an independent prognostic factor and a serviceable therapeutic target in LGG. [ABSTRACT FROM AUTHOR]

Simple Summary: Despite the recent advancement in the treatment of ovarian cancer, it continues to be a largely incurable disease, plagued by de novo and acquired resistance to standard chemotherapeutics and novel second-line therapeutics. Therefore, identifying novel biomarkers and resistance mechanisms is critical to overcoming resistance, developing newer treatment strategies, and improving patient survival. In this study, we have demonstrated that low Caspase-8 expression correlates with poor prognosis in ovarian cancer patients. Moreover, the lack of Caspase-8 alters transcriptional regulation in ovarian cancer cells. In Caspase-8 knockout cells, increased BRD4 expression, increased CDK9 activity, and resistance to Carboplatin and Paclitaxel were observed. We have also shown that combining BRD4 inhibitors with Carboplatin, Paclitaxel, and CDK9 inhibitors synergistically sensitized these cells to undergo cell death. Ovarian cancer is one of the most lethal gynecological cancers worldwide, with approximately 70% of cases diagnosed in advanced stages. This late diagnosis results from the absence of early warning symptoms and is associated with an unfavorable prognosis. A standard treatment entails a combination of primary chemotherapy with platinum and taxane agents. Tumor recurrence following first-line chemotherapy with Carboplatin and Paclitaxel is detected in 80% of advanced ovarian cancer patients, with disease relapse occurring within 2 years of initial treatment. Platinum-resistant ovarian cancer is one of the biggest challenges in treating patients. Second-line treatments involve PARP or VEGF inhibitors. Identifying novel biomarkers and resistance mechanisms is critical to overcoming resistance, developing newer treatment strategies, and improving patient survival. In this study, we have determined that low Caspase-8 expression in ovarian cancer patients leads to poor prognosis. High-Grade Serous Ovarian Cancer (HGSOC) cells lacking Caspase-8 expression showed an altered composition of the RNA Polymerase II-containing transcriptional elongation complex leading to increased transcriptional activity. Caspase-8 knockout cells display increased BRD4 expression and CDK9 activity and reduced sensitivities to Carboplatin and Paclitaxel. Based on our work, we are proposing three potential therapeutic approaches to treat advanced ovarian cancer patients who exhibit low Caspase-8 expression and resistance to Carboplatin and/or Paclitaxel—combinations of (1) Carboplatin with small-molecule BRD4 inhibitors; (2) Paclitaxel with small-molecule BRD4 inhibitors, and (3) small-molecule BRD4 and CDK9 inhibitors. In addition, we are also proposing two predictive markers of chemoresistance—BRD4 and pCDK9. [ABSTRACT FROM AUTHOR]

Objective: This study aims to evaluate chemotherapy-related mania in cancer patients. Methods: The mania status of 153 cancer patients who received chemotherapy was compared by applying the Young Mania Rating Scale before starting chemotherapy and after one session of the chemotherapy regimen. Results: When the mania total scores before and after treatment were compared according to the chemotherapeutic agents, it was seen that the post-treatment mania total scores increased in those using Fluorouracil-Folinic Acid-Oxaliplatin (Folfox) (p=0.014) and paclitaxel (p=0.036) chemotherapy regimens. In 8 (5.2%) patients who received the Folfox regimen, the mild mania score exceeded 20 points. Conclusions: Although the blood-brain barrier protects the central nervous system from the toxicity of many drugs, it is known that the stress of cancer diagnosis and some chemotherapeutics used in treatment cause disorders such as acute confusion, depression, and mania. In our study, as in case-based publications in the literature, a statistically significant increase in the total mania score was found in the Folfox regimen due to 5-fluorouracil's ability to cross the blood-brain barrier easily. According to published case reports in the literature, the possibility of mania symptoms appearing in the second, third, and sometimes subsequent sessions should be taken into consideration due to cumulative or delayed side effects of the drugs. Keywords: Cancer patients, Mania, Chemotherapeutics, Risk. [ABSTRACT FROM AUTHOR]

Nanotechnology provides effective methods for precisely delivering chemotherapeutics to cancer cells, thereby improving efficacy and reducing off-target side effects. The targeted delivery of nanoscale chemotherapeutics is accomplished by two different approaches, namely the exploitation of leaky tumor vasculature (EPR effect) and the surface modification of nanoparticles (NPs) with various tumor-homing peptides, aptamers, oligonucleotides, and monoclonal antibodies (mAbs). Because of higher binding affinity and specificity, mAbs have received a lot of attention for the detection of selective cancer biomarkers and also for the treatment of various types of cancer. Antibody-conjugated nanoparticles (ACNPs) are an effective targeted therapy for the efficient delivery of chemotherapeutics specifically to the targeted cancer cells. ACNPs combine the benefits of NPs and mAbs to provide high drug loads at the tumor site with better selectivity and delivery efficiency. The mAbs on the NP surfaces recognize their specific receptors expressed on the target cells and release the chemotherapeutic agent in a controlled manner. Appropriately designed and synthesized ACNPs are essential to fully realize their therapeutic benefits. In blood stream, ACNPs instantly interact with biological molecules, and a protein corona is formed. Protein corona formation triggers an immune response and affects the targeting ability of the nanoformulation. In this review, we provide recent findings to highlight several antibody conjugation methods such as adsorption, covalent conjugation, and biotin–avidin interaction. This review also provides an overview of the many effects of the protein corona and the theranostic applications of ACNPs for the treatment of cancer.

Implantable drug delivery systems formed upon injection offer a host of advantages, including localized drug administration, sustained release, minimized side effects, and enhanced patient compliance. Among the various techniques utilized for the development of in situ forming drug implants, solvent-induced phase inversion emerges as a particularly promising approach. However, synthetic polymer-based implants have been associated with undesirable effects arising from polymer degradation. In response to this challenge, a novel category of drug delivery systems, known as phospholipids-based phase separation gels (PPSGs), has emerged. These gels, characterized by their low initial viscosity, exhibit injectability and undergo rapid transformation into in situ implants when exposed to an aqueous environment. A typical PPSG formulation comprises biodegradable components, such as phospholipids, pharmaceutical oil, and a minimal amount of ethanol. The minimized organic solvents in the composition show good biocompatibility. And the relatively simple composition holds promise for industrial-scale manufacturing. This comprehensive review provides an overview of the principles and advancements in PPSG systems, with specific emphasis on their suitability as drug delivery systems for a wide range of active pharmaceutical ingredients (APIs), spanning from small molecules to peptides and proteins. Additionally, we explore the critical parameters and underlying principles governing the formulation of PPSG-based drug delivery strategies, offering valuable insights on optimization strategies.

Abstract Cancer is a grievous disease whose treatment requires a more efficient, non-invasive therapy, associated with minimal side effects. Gold nanoparticles possessing greatly impressive optical properties have been a forerunner in bioengineered cancer therapy. This theranostic system has gained immense popularity and finds its application in the field of molecular detection, biological imaging, cancer cell targeting, etc. The photothermal property of nanoparticles, especially of gold nanorods, causes absorption of the light incident by the light source, and transforms it into heat, resulting in tumor cell destruction. This review describes the different optical features of gold nanoparticles and summarizes the advance research done for the application of gold nanoparticles and precisely gold nanorods for combating various cancers including breast, lung, colon, oral, prostate, and pancreatic cancer.

The treatment of central nervous system (CNS) tumors is complicated by high rates of recurrence and treatment resistance that contribute to high morbidity and mortality (Nat Rev Neurol. 2022;18:221–36. doi: 10.1038/s41582-022-00621-0). One of the challenges of treating these tumors is the limited permeability of the blood brain barrier (BBB). Early pharmacologic treatments worked to overcome the BBB by targeting vulnerabilities in the tumor cell replication process directly through alkylating agents like temozolomide. However, as advancements have been made options have expanded to include immunologic targets through the use of monoclonal antibodies. In the future, treatment will likely continue to focus on the use of immunotherapies, as well as emerging technology like the use of low-intensity focused ultrasound (LIFU). Ultimately, this paper serves as an introductory overview of current therapeutic options for post-resection primary brain tumors, as well as a look towards future work and emerging treatment options.

The green synthesis of gold nanoparticles (Au NPs) using extracts or active ingredients from traditional Chinese medicine presents a novel approach characterized by simplicity, environmental friendliness, and independence from specific conditions. This innovative method combines the photothermal conversion properties of Au NPs with the chemotherapeutic effects of traditional Chinese medicine components, significantly enhancing anticancer efficacy. Celastrol (Cel), an effective medicinal ingredient extracted from the traditional Chinese herb Tripterygium wilfordii Hook. f. (TW), exhibits outstanding anticancer properties. In this study, Cel was successfully employed for the novel green synthesis of gold nanoparticles, forming Cel-Au NPs with a particle size of 50[Formula: see text]nm. Cel-Au NPs demonstrated excellent photothermal responsiveness, thermostability, and biocompatibility. The cytotoxicity of Cel-Au NPs on A549 cells reached approximately 80% upon exposure to 808[Formula: see text]nm near-infrared (NIR) irradiation. The anticancer activity was attributed to the induction of apoptosis and necrosis, achieved by elevating intracellular reactive oxygen species (ROS) levels and modulating the expression of apoptosis-related proteins. In conclusion, our synthesized Cel-Au NPs exhibited exceptional capabilities in chemotherapy and photothermal therapy, demonstrating excellent therapeutic efficacy and safety for cancer treatment.

Two piano‐stool ruthenium(II) complexes Ru(η6‐p‐cymene)Cl2PPh2CH2OH (RuPOH) and Ru(η6‐p‐cymene)Cl2P(p‐OCH3Ph)2CH2OH (RuMPOH) and two half‐sandwich iridium(III) complexes Ir(η5‐Cp*)Cl2PPh2CH2OH (IrPOH) and Ir(η5‐Cp*)Cl2P(p‐OCH3Ph)2CH2OH (IrMPOH) have been studied in terms of potential anticancer activity on previously selected cell line (human lung adenocarcinoma). Based on experimental results obtained in monoculture in vitro model mechanistic considerations on the possible cellular modes of action have been carried out. ICP‐MS analysis revealed the higher cellular uptake for less hydrophobic Ir(III) complexes in comparison to the corresponding Ru(II) compounds. Cytometric analysis showed a predominance of apoptosis over the other types of cell death for all complexes. The apoptotic pathway was confirmed by a decrease in mitochondrial membrane potential and the activation of caspases‐3/9 for both Ru(II) and Ir(III) complexes. It was concluded that in the case of Ru(II) complexes the intense ROS generation is mainly responsible for the resulting cytotoxicity. The corresponding Ir(III) complexes trigger simultaneously at least three different cytotoxic pathways i. e., depletion of mitochondrial potential, activation of caspases‐dependent apoptosis, and ROS‐associated oxidation. Thus, it can be assumed that the final accumulation of toxic effects over time via parallel activation of different pathways results in the highest cytotoxicity in vitro exhibited by Ir(III) complexes when compared with Ru(II) complexes. [ABSTRACT FROM AUTHOR]

New heterometallic binuclear and trinuclear platinum(IV)–gold(I) compounds of the type [Pt(L)nCl2(OH){(OOC‐4‐C6H4‐PPh2)AuCl}x] (L=NH3, n=2; x=1, 2; L=diaminocyclohexane, DACH, n=1; x=2) are described. These compounds are cytotoxic and selective against a small panel of renal, bladder, ovarian, and breast cancer cell lines. We selected a trinuclear PtAu2 compound containing the PtIV core based on oxaliplatin, to further investigate its cell‐death pathway, cell and organelle uptake and anticancer effects against the triple‐negative breast cancer (TNBC) MDA‐MB‐231 cell line. This compound induces apoptosis and accumulates mainly in the nucleus and mitochondria. It also exerts remarkable antimigratory and antiangiogenic properties, and has a potent cytotoxic effect against TNBC 3D spheroids. Trinuclear compounds do not seem to display relevant interactions with calf thymus (CT) DNA and plasmid (pBR322) even in the presence of reducing agents, but inhibit pro‐angiogenic enzyme thioredoxin reductase (TrxR) in TNBC cells. [ABSTRACT FROM AUTHOR]

Aquaculture is a promising food sector to fulfil nutritional requirements of growing human population. Live weight aquaculture production reached up to 114.5 million tonnes in 2018 and it is further expected to grow by 32% by year 2030. Among total aquaculture production, major product harvested is finfish and its contribution has reached 46% in recent years. Frequent outbreaks of infectious diseases create obstacle in finfish production, result in economic losses to the farmers and threaten the sustainability of aquaculture industry itself. In spite of following the best management practices, the use of antibiotics, chemotherapeutics and phytochemicals often become the method of choice in finfish culture. Among these, phytochemicals have shown lesser effect in animal welfare while antibiotics and other chemotherapeutics have led to negative consequences like emergence of drug-resistant bacteria, and accumulation of residues in host and culture system, resulting in quality degradation of aqua products. Making use of probiotics as viable alternative has paved a way for sustainable aquaculture and minimise the use of antibiotics and other chemotherapeutics that pose adverse effect on host and culture system. This review paper elucidates the knowledge about antibiotics and other chemicals, compilation of probiotics and their effects on health status of finfish as well as overall culture environment. Besides, concoction of probiotics and prebiotics for simultaneous application has also been discussed briefly. [ABSTRACT FROM AUTHOR]

Supramolecular assemblies fabricated by peptide-photosensitizer conjugates have attracted increasing attentions in recent years as drug carriers for chemotherapeutics (CTs). However, these assemblies have been known to suffer from disintegration by serum components leading to off-target drug release, and thereby impairing antitumor effects and causing systemic toxicities. To address this problem, this study reports a nano-architectural self-assembly peptide-photosensitizer carrier (NSPC) fabricated by conjugating a phthalocyanine derivative (MCPZnPc) and ε-poly- l -lysine (EPL). By engineering the core and peripheral interactions, MCPZnPC-EPL (M−E) NSPC firmly encapsulated multiple CTs, creating CT@M−E NSPCs that were highly stable against disintegration in serum. More importantly, CT@M−E NSPCs exhibited controlled release of CTs in tumor tissues. The antitumor effects of CTs were further promoted by the synergism with the reactivated photodynamic effect. Furthermore, M−E NSPC-encapsulation optimized CTs' biodistribution reducing adverse effects in vivo. This study provides a serum-stable supramolecular drug delivery system with photodynamic effect, which is applicable for a broad-range of CTs to promote antitumor effects and ameliorate adverse effects. [ABSTRACT FROM AUTHOR]

Head and neck squamous cell carcinoma (HNSCC) is a type of cancer that arises from the epithelium lining of the oral cavity, hypopharynx, oropharynx, and larynx. Despite the advancement of current treatments, including surgery, chemotherapy, and radiotherapy, the overall survival rate of patients afflicted with HNSCC remains poor. The reasons for these poor outcomes are due to late diagnoses and patient-acquired resistance to treatment. Natural products have been extensively explored as a safer and more acceptable alternative therapy to the current treatments, with numerous studies displaying their potential against HNSCC. This review highlights preclinical studies in the past 5 years involving natural products against HNSCC and explores the signaling pathways altered by these products. This review also addresses challenges and future directions of natural products as chemotherapeutic and chemoprevention agents against HNSCC. [ABSTRACT FROM AUTHOR]

Abstract Background Choosing the most effective chemotherapeutic agent with safest side effect profile is a common challenge in cancer treatment. Although there are standardized chemotherapy protocols in place, protocol changes made after extensive clinical trials demonstrate significant improvement in the efficacy and tolerability of certain drugs. The pharmacokinetics, pharmacodynamics, and tolerance of anti‐cancer medications are all highly individualized. A driving force behind these differences lies within a person's genetic makeup. Recent findings Pharmacogenomics, the study of how an individual's genes impact the processing and action of a drug, can optimize drug responsiveness and reduce toxicities by creating a customized medication regimen. However, these differences are rarely considered in the initial determination of standardized chemotherapeutic protocols and treatment algorithms. Because pharmacoethnicity is influenced by both genetic and nongenetic variables, clinical data highlighting disparities in the frequency of polymorphisms between different ethnicities is steadily growing. Recent data suggests that ethnic variations in the expression of allelic variants may result in different pharmacokinetic properties of the anti‐cancer medication. In this article, the clinical outcomes of various chemotherapy classes in patients of different ethnicities were reviewed. Conclusion Genetic and nongenetic variables contribute to the interindividual variability in response to chemotherapeutic drugs. Considering pharmacoethnicity in the initial determination of standard chemotherapeutic protocols and treatment algorithms can lead to better clinical outcomes of patients of different ethnicities.

Intra‐tumor bacteria promote tumor growth and inactivate cancer‐chemotherapeutics, causing poor treatment prognoses. Combined administration of cancer‐chemotherapeutics and antibiotics may disturb the oral and intestinal microflora in critically‐ill patients. To establish intra‐tumor co‐delivery of cancer‐chemotherapeutics and antibiotics, gemcitabine and ciprofloxacin are loaded in so‐called "self‐targeting", highly blood‐compatible, synthetic DCPA‐H2O liposomes equipped with complexed water for pH‐responsiveness. Liposomal pH‐responsiveness can be maintained by in‐shell loading of gemcitabine and in‐core loading of ciprofloxacin. These dual‐loaded liposomes are stealthily transported in the blood circulation to accumulate in the acidic environment of an infected tumor. Upon tumor self‐targeting, liposomes are fused with tumor cells and infecting bacteria and are disassembled to simultaneously release gemcitabine and ciprofloxacin. Treatment of mice with these self‐targeting liposomes yields significantly higher responses of Escherichia coli infected tumors with respect to both infection and tumor volume than gemcitabine and ciprofloxacin co‐delivered from non‐self‐targeting liposomes or free gemcitabine with or without ciprofloxacin in solution. [ABSTRACT FROM AUTHOR]

Effective extravasation of therapeutic agents into solid tumors still faces huge challenges. Since the doubted effectiveness of enhanced penetration and retention effect, first-generation neutrophil cytopharmaceuticals with encapsulated drugs have been developed to improve the drug accumulation in tumors based on the active chemotaxis and extravasation of neutrophils. Herein, a new generation of neutrophil cytopharmaceuticals with enhanced tumor-specific extravasation is reported to satisfy more complex clinical demands. This neutrophil cytopharmaceutical is obtained by anchoring vascular endothelial growth factor receptor 2 (VEGFR2)-targeting peptide K237 on neutrophil membrane after endocytosis of chemotherapeutics by neutrophils. Leveraging the cytokine-mediated active migration of neutrophils, the specific-recognition of K237 peptide to tumor vascular endothelium expedites the migration and enhances tight adhesion of neutrophils to vascular endothelium, thus improving the extravasation of therapeutic agents to target sites. Moreover, anti-angiogenesis effect from VEGFR2-blocking by K237 peptide achieves a cooperative tumor destruction with cytotoxic effects from released chemotherapeutics. This study demonstrates the great potential of enhanced proactive extravasation of cytopharmaceuticals via a cell-anchoring technology, leading to expedited drug infiltration and boosted therapeutic effects, which can be applied in other cell therapies to improve efficacy. A more powerful neutrophil cytopharmaceuticals with enhanced extravasation is developed to exhibit an accelerated targeting and extensive extravasation from tumor vessels, thus achieving more highly-efficient drug delivery and tumor killing. [Display omitted] • The enhanced tumor-extravasation is necessary for neutrophils cytopharmaceuticals. • Membrane-anchored K237 peptide expedites the neutrophils extravasation into tumor. • Neutrophils cytopharmaceuticals K237-PNEs performs synergistic antitumor effect. • Membrane-anchoring technic constructs new-generation of cytopharmaceuticals. [ABSTRACT FROM AUTHOR]

Cancer is a grievous disease whose treatment requires a more efficient, non-invasive therapy, associated with minimal side effects. Gold nanoparticles possessing greatly impressive optical properties have been a forerunner in bioengineered cancer therapy. This theranostic system has gained immense popularity and finds its application in the field of molecular detection, biological imaging, cancer cell targeting, etc. The photothermal property of nanoparticles, especially of gold nanorods, causes absorption of the light incident by the light source, and transforms it into heat, resulting in tumor cell destruction. This review describes the different optical features of gold nanoparticles and summarizes the advance research done for the application of gold nanoparticles and precisely gold nanorods for combating various cancers including breast, lung, colon, oral, prostate, and pancreatic cancer. [ABSTRACT FROM AUTHOR]

(1) The treatment of metastatic or drug-resistant melanoma is still a significant therapeutic problem. The aim of this study was to evaluate the anticancer potential of daphnetin (7,8-dihydroxycoumarin) and its combinations with five different cytostatic drugs (mitoxantrone, docetaxel, vemurafenib, epirubicin and cisplatin). (2) The viability, proliferation and cytotoxicity of daphnetin against four human malignant melanoma cell lines were evaluated. The interactions were assessed using isobolographic analysis for the combinations of daphnetin with each of the five cytostatic drugs. (3) Daphnetin showed anticancer activity against malignant melanoma, with IC50 values ranging from 40.48 ± 10.90 µM to 183.97 ± 18.82 µM, depending on the cell line. The combination of daphnetin with either vemurafenib or epirubicin showed an antagonistic interaction. Moreover, additive interactions were observed for the combinations of daphnetin with cisplatin and docetaxel. The most desirable synergistic interactions for human melanoma metastatic cell lines were observed for the combination of daphnetin with mitoxantrone. (4) The obtained results suggest that daphnetin should not be combined with vemurafenib or epirubicin in the treatment of malignant melanoma due to the abolition of their anticancer effects. The combination of daphnetin with mitoxantrone is beneficial in the treatment of metastatic melanoma due to their synergistic interaction. [ABSTRACT FROM AUTHOR]

SARS-CoV-2 Main protease (Mpro) is pivotal in viral replication and transcription. Mpro mediates proteolysis of translated products of replicase genes ORF1a and ORF1ab. Surveying pre-clinical trial Mpro inhibitors suggests potential enhanced efficacy for some moieties. Concordant with promising in vitro and in silico data, the protease inhibitor GC376 was chosen as a lead. Modification of GC376 analogues yielded a series of promising Mpro inhibitors. Design optimization identified compound G59i as lead candidate, displaying a binding energy of − 10.54 kcal/mol for the complex. Robust interactivity was noted between G59i and Mpro. With commendable ADMET characteristics and enhanced potency, further G59i analysis may be advantageous; moreover, identified key Mpro residues could contribute to the design of neotenic inhibitors. Serial modifications to the SARS-2-CoV main protease (Mpro) inhibitor GC376 yielded promising analogues from which compound G59i was progressed. A more exothermic binding energy was predicted for Mpro ligation compared to GC376. With commendable ADMET characteristics and enhanced potency, further G59i analysis may be advantageous. [ABSTRACT FROM AUTHOR]

Abstract Although colorectal cancer (CRC) treatment has seen a remarkable improvement in the recent years, many patients will develop metastasis due to the resistance of cancer cells to chemotherapeutics. Targeting mechanisms driving the resistance of CRC cells to treatment would significantly reduce cases of metastasis and death. Induction of insulin‐like growth factor 2 mRNA‐binding protein 1 (IGF2BP1), a direct target of the Wnt/β‐catenin signaling pathway, might promote resistance of CRC cells to treatment via activation of anti‐apoptotic pathways and induction of the multidrug resistance (MDR1) membrane transporter that pumps drugs out of the cells. We hypothesized that inhibition of IGF2BP1 will sensitize CRC cells to chemotherapeutics. We used CRC cell lines with different status of activation of Wnt signaling to show that inhibition of IGF2BP1 potentiates the anti‐growth and anti‐proliferative effects of chemotherapeutics on CRC cells with activated Wnt/β‐catenin signaling pathway. We observed that the inhibition of IGF2BP1 significantly increases apoptosis in the same cells. A remarkable reduction in the migratory capability of those cells was noted as well. We found that inhibition of IGF2BP1 is sufficient to decrease the resistance of chemotherapy‐resistant cancer cells with activated Wnt/β‐catenin signaling pathway. These findings portray IGF2BP1 as a good candidate for CRC therapy.

Taxifolin is a flavonoid compound, originally isolated from the bark of Douglas fir trees, which is often found in foods such as onions and olive oil, and is also used in commercial preparations, and has attracted the interest of nutritionists and medicinal chemists due to its broad range of health-promoting effects. It is a powerful antioxidant with excellent antioxidant, anti-inflammatory, anti-microbial and other pharmacological activities. This review focuses on the breakthroughs in taxifolin for the treatment of diseases from 2019 to 2022 according to various systems of the human body, such as the nervous system, immune system, and digestive system, and on the basis of this review, we summarize the problems of current research and try to suggest solutions and future research directions. [ABSTRACT FROM AUTHOR]