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Angiogenesis involves the development of new blood vessels from the pre-existing vasculature. In cancer, an inappropriate or pathological angiogenesis reinforces tumor growth by feeding with nutrient and oxygen. Central to the process of angiogenesis is vascular endothelial growth factor (VEGF) and its receptor (VEGFR), as they regulate angiogenesis and vascular permeability. To stop tumor angiogenesis by cutting off the blood supply, a multitude of angiogenesis inhibitors (antiangiogenic agents or anticancer drugs) have been developed. In pursuit of developing an effective angiogenesis inhibitor, a novel pyrimidine derivative, an inhibitor of VEGFR-2 kinase activity later known as "VOTRIENT (Pazopanib)" was developed by GlaxoSmithKline and approved by the FDA in October 2009 for treatment of advanced renal cell cancer. Later, it was also approved by the FDA for the treatment of advanced soft tissue sarcoma in April 2012. In the literature, there are multiple synthetic pathways reported and the present work reviews the literature related to the synthesis of Pazopanib emphasizing applicability at a commercial scale. The main purpose of this review paper is to provide a comprehensive overview of different existing routes of synthesis with relevant comparison, reported polymorphs, and suggesting further development. [ABSTRACT FROM AUTHOR]

The field of oncology has witnessed remarkable progress in personalized cancer therapy. Functional precision medicine has emerged as a promising avenue for achieving superior treatment outcomes by integrating omics profiling and sensitivity testing of patient-derived cancer cells. This review paper provides an in-depth analysis of the evolution of cancer-directed drugs, resistance mechanisms, and the role of functional precision medicine platforms in revolutionizing individualized treatment strategies. Using two-dimensional (2D) and three-dimensional (3D) cell cultures, patient-derived xenograft (PDX) models, and advanced functional assays has significantly improved our understanding of tumor behavior and drug response. This progress will lead to identifying more effective treatments for more patients. Considering the limited eligibility of patients based on a genome-targeted approach for receiving targeted therapy, functional precision medicine provides unprecedented opportunities for customizing medical interventions according to individual patient traits and individual drug responses. This review delineates the current landscape, explores limitations, and presents future perspectives to inspire ongoing advancements in functional precision medicine for personalized cancer therapy. [ABSTRACT FROM AUTHOR]

Lung cancer is the leading cause of cancer-related mortality worldwide, largely due to the limited efficacy of anticancer drugs, which is primarily attributed to insufficient doses reaching the lungs. Additionally, patients undergoing treatment experience severe systemic adverse effects due to the distribution of anticancer drugs to non-targeted sites. In light of these challenges, there has been a growing interest in pulmonary administration of drugs for the treatment of lung cancer. This route allows drugs to be delivered directly to the lungs, resulting in high local concentrations that can enhance antitumor efficacy while mitigating systemic toxic effects. However, pulmonary administration poses the challenge of overcoming the mechanical, chemical, and immunological defenses of the respiratory tract that prevent the inhaled drug from properly penetrating the lungs. To overcome these drawbacks, the use of nanoparticles in inhaler formulations may be a promising strategy. Nanoparticles can assist in minimizing drug clearance, increasing penetration into the lung epithelium, and enhancing cellular uptake. They can also facilitate increased drug stability, promote controlled drug release, and delivery to target sites, such as the tumor environment. Among them, chitosan-based nanoparticles demonstrate advantages over other polymeric nanocarriers due to their unique biological properties, including antitumor activity and mucoadhesive capacity. These properties have the potential to enhance the efficacy of the drug when administered via the pulmonary route. In view of the above, this paper provides an overview of the research conducted on the delivery of anticancer drug-loaded chitosan-based nanoparticles incorporated into inhaled drug delivery devices for the treatment of lung cancer. Furthermore, the article addresses the use of emerging technologies, such as siRNA (small interfering RNA), in the context of lung cancer therapy. Particularly, recent studies employing chitosan-based nanoparticles for siRNA delivery via the pulmonary route are described. [ABSTRACT FROM AUTHOR]

Cisplatin-based metallodrugs are traditionally utilized as anticancer agents. Nonetheless, these drugs have adverse effects on normal tissues since cisplatin eliminates the body amid cancerous growth cells by destroying the sequence of genomic DNA. As a result, the metallodrug structure demonstrated numerous antagonistic behaviours to the malignant tumour development system associated with nucleic acid G-quadruplex. This paper systematically explored the development of successful procedures and competent anticancer drugs that expressly collaborate, resolve, or divide G4 structures. In the therapeutic domain, we highlighted the cutting-edge G4-metallo-structures, their interface mechanisms, and the potential for use as anticancer medicines. Furthermore, this paper also describes the methodologies utilized to discriminate the binding capacity between G-quadruplex and metallo-structures. This review will help to create metallodrugs from the most significant electrical supplementary design specification to a progressively logical bio-science level. [ABSTRACT FROM AUTHOR]

Antimicrobial peptides (AMPs), commonly referred to as host defense peptides, are found in a wide range of organisms, including bacteria, plants, and both vertebrate and invertebrate animals. They function as an initial defense mechanism against pathogenic microorganisms, modulate immune responses, and in specific instances, confer protection against the onset of cancer. Pleurocidin (Ple) is a linear antimicrobial peptide with amphipathic a-helical conformation, isolated originally from the winter flounder (Pleuronectes americanus), notable for its wide-ranging effectiveness against both bacteria and fungi. While the majority of research on pleurocidin's biological characteristics has primarily focused on deciphering its mechanisms of interaction with the biological membranes of pathogenic bacteria and host cells, as well as investigating its modes of killing activities, there is a growing body of evidence suggesting that pleurocidin and pleurocidin-derived analogs might be effectively employed as anti-cancer agents against breast carcinoma and leukemia due to their potent cytotoxic properties and selectivity towards cancer cells. Notably, some characteristics of pleurocidin observed in microbiological investigations of this compound could be effectively applied in examining the anti-cancer capabilities of Ple-like derivatives. This review provides a comprehensive overview of the literature on the biological activities of pleurocidin, pleurocidin-derived peptides, pleurocidin-containing hybrid peptides, and nanosystems. The primary emphasis is on elucidating the range of activities exhibited by these compounds, evaluating their potential therapeutic applications, assessing their safety profile, and identifying any limits observed thus far. This paper will also discuss potential areas for further investigation into the anti-cancer effects of Ple and its derivatives, drawing insights from microbiological research. [ABSTRACT FROM AUTHOR]

Pt(IV) prodrugs have been extensively studied over the years with the aim of overcoming the limitations of traditional Pt(II) drugs. In this frame, two cisplatin-based Pt(IV) complexes bearing α-tocopherol succinate (α-TOS, a derivative of vitamin E) in the axial position (namely, [PtCl2(NH3)2(OEt)(α-TOS)] and [PtCl2(NH3)2(α-TOS)2] were reported in recent years and their cytotoxicity was evaluated. In particular, [PtCl2(NH3)2(OEt)(α-TOS)] was reported to be more cytotoxic than [PtCl2(NH3)2(α-TOS)2]. In the present comment paper, reasons for the different cytotoxicity of these complexes are discussed in detail and, more in general, a comprehensive elucidation of the mechanism of action of this class of anticancer Pt(IV) compounds is provided. Hopefully, these findings and the resulting improved knowledge of these drugs will help researchers design new and improved Pt(IV) anticancer drugs. [ABSTRACT FROM AUTHOR]

Background: The U.S. Food and Drug Administration (FDA) and European Medicines Agency (EMA) have published guidelines on the use of cancer treatments in young people of reproductive potential. However, no such guideline is available in Japan. Therefore, this project aimed to gather relevant data and draft a respective guidance paper. Methods: From April 2019 to March 2021, the Study Group for Providing Information on the Proper Use of Pharmaceuticals in Patients with Reproductive Potential at the Japan Agency for Medical Research and Development gathered opinions from experts in reproductive medicine, toxicology, and drug safety measures. The group considered these opinions, the FDA and EMA guidelines, and relevant Japanese guidelines and prepared a guidance paper, which they sent to 19 related organizations for comment. Results: By November 2020, the draft guidance paper was completed and sent to the related organizations, 17 of which provided a total of 156 comments. The study group finalized the guidance paper in March 2021. Conclusions: The "Guidance on the Need for Contraception Related to Use of Pharmaceuticals" (The report of the Study Group for Providing Information on the Proper Use of Pharmaceuticals in Patients with Reproductive Potential, Research on Regulatory Science of Pharmaceuticals and Medical Devices, Japan Agency for Medical Research and Development: JP20mk0101139) is expected to help Japanese healthcare professionals provide fertility-related care and advice to adolescents, and young adults with cancer and their families. [ABSTRACT FROM AUTHOR]

This article is an editorial that discusses the potential of natural products and nanoparticles in cancer treatment. It highlights the challenges faced in utilizing natural products for medicinal purposes, such as poor solubility and bioavailability. Nanoparticles, on the other hand, offer unique properties that allow for precise targeting of tumors and reduced impact on healthy tissues. The article also mentions specific studies that explore the application of nanoparticles in targeted therapy for different types of cancer. Overall, the article emphasizes the need for further research in this field to enhance the effectiveness of cancer treatments. [Extracted from the article]

Chitosan is a positively charged polysaccharide obtained through chitin deacetylation. It belongs to a group of biodegradable, bioavailable, and non-toxic materials of natural origin; thus, it is a promising matrix for creating delivery systems of different active agents. Recently, much attention has been paid to nanodelivery systems as carriers to enable better bioavailability, and thus higher efficiency of the loaded drug. The present review is focused on the progress in chitosan-based nanoparticles for the targeted delivery of antitumor drugs. The paper discusses literature reports from the last three years in which chitosan nanoparticles were applied as carriers for active substances used in antitumor therapy and potential new drugs with anticancer properties. Special attention was paid to the different treatments applied to increase the therapeutic effectiveness and minimize the side effects of a specific active substance. [ABSTRACT FROM AUTHOR]

Anticancer drugs are one of the most direct means of cancer therapy. However, the various cancer progressions hamper the development and discovery of anticancer drugs. In fact, the mechanical properties of the tumor cytoskeleton are extremely vital for any phase of cancer, especially in tumor invasion and metastasis. However, in the current category of anticancer drugs, the cytoskeleton-targeting drugs are limited and their role in tumor progression is unclear. Here, we present the mechanical characteristics of tumor stiffness that are tightly regulated by the cancer cytoskeleton, including actin filaments and microtubules during tumor initiation, growth and metastasis, and review the natural drugs that target the cancer cytoskeleton. We define cytoskeleton dynamics as target mechanisms for anticancer drugs and summarize the plant, microbial and marine sources of natural products. Furthermore, this paper also provides a material pathway to study active tumor mechanics, and introduces the unique advantages and future application potential of tumor cytoskeleton-targeting drugs in clinical use. The material approaches to active cancer mechanics are supplied in this review. We aim to promote the development of anticancer drugs that target tumor mechanics by using those material approaches and finding their pharmacological application. [ABSTRACT FROM AUTHOR]

For a simple graph with vertex set { v 1 , v 2 , ... , v n } with degree sequence d v i of vertex v i , i = 1 , 2 , ... , n , the inverse sum indeg matrix ( I S I -matrix) A I S I (G) = (a i j) n × n of G is defined by a i j = d v i d v j d v i + d v j , if v i is adjacent to v j , and zero, otherwise. The multiset of eigenvalues of A I S I (G) is the I S I -spectrum of G and the sum of their absolute values is the I S I -energy of G . In this paper, we modify the two results of (Li, Ye and Broersma, 2022), give the correct characterization of the extremal graphs and thereby obtain better bounds than the already known results. Moreover, we also discuss the QSPR analysis and carry the statistical modelling (linear, logarithmic and quadratic) of the physicochemical properties of anticancer drugs with the I S I -index (energy). [ABSTRACT FROM AUTHOR]

Graphene and its derivatives are frequently used in cancer therapy, and there has been widespread interest in improving the therapeutic efficiency of targeted drugs. In this paper, the geometrical structure and electronic effects of anastrozole(Anas), camptothecin(CPT), gefitinib (Gefi), and resveratrol (Res) on graphene and graphene oxide(GO) were investigated by density functional theory (DFT) calculations and molecular dynamics (MD) simulation. Meanwhile, we explored and compared the adsorption process between graphene/GO and four drug molecules, as well as the adsorption sites between carriers and payloads. In addition, we calculated the interaction forces between four drug molecules and graphene. We believe that this work will contribute to deepening the understanding of the loading behaviors of anticancer drugs onto nanomaterials and their interaction. [ABSTRACT FROM AUTHOR]

A wide range of new drugs emerge each year with the rapid development of the manufacture of medicines. Once the indicators of these drug molecular structures are calculated in view of defining the topological indices, these can be used to understand their medical properties. In this paper, based on the drug molecular structure analysis, we compute the multiplicative sum connectivity index, the multiplicative Randić index, the multiplicative atomic bond connectivity index, the multiplicative Geometric arithmetic index, the multiplicative Harmonic index and the multiplicative augmented Zagreb index for the molecular structure anticancer drugs SP[n]. Finally, we used Maple 15 to plot surfaces associated to compare our results. [ABSTRACT FROM AUTHOR]

Currently, cancer is the most rapidly growing life-threatening disease after cardiovascular in the world, posing a major threat to human life. Telomerase promotes tumorigenesis and development in most cancers and dyskerin plays a crucial role in telomere maintenance. Cancer molecules are being developed continuously as a result of continuous research. A series of novel anticancer agents have been developed using telomerase inhibitors with improved specificity and pharmacokinetics. As medicinal chemistry advances, heterocyclic-based drugs find increasing applications, including anticancer agents. These properties have led to the development of five-membered aromatic rings of oxadiazoles. In order to enhance their anticancer activity, oxadiazole scaffolds can be modified. In this review, we discuss the functions and mechanism of action of the telomerase enzyme. The paper also summarizes the interaction between 1,3,4-oxadiazole inhibitors and telomerase enzymes. [ABSTRACT FROM AUTHOR]

Actin is the structural protein of microfilaments, and it usually exists in two forms: monomer and polymer. Among them, monomer actin is a spherical molecule composed of a polypeptide chain, also known as spherical actin. The function of actin polymers is to produce actin filaments, so it is also called fibroactin. The actin cytoskeleton is considered to be an important subcellular filament system. It interacts with numerous relevant proteins and regulatory cells, regulating basic functions, from cell division and muscle contraction to cell movement and ensuring tissue integrity. The dynamic reorganization of the actin cytoskeleton has immense influence on the progression and metastasis of cancer as well. This paper explores the significance of the microfilament network, the dynamic changes of its structure and function in the presence of a tumor, the formation process around the actin system, and the relevant proteins that may be target molecules for anticancer drugs so as to provide support and reference for interlinked cancer treatment research in the future. [ABSTRACT FROM AUTHOR]

Background: Cancer is one of the diseases with high mortality rate recorded each year across the world. Its mainstay treatment is chemotherapy although they are largely toxic, causing severe adverse reactions including cardiotoxicity, nephrotoxicity and genotoxicity. Cardiotoxicity is unique to certain chemotherapeutic agents and occur via several mechanisms. It has been hypothesized that co-administration of natural products which may be cardioprotectant, together with chemotherapy can alleviate cardiotoxicity-induced by chemotherapy. Objectives: This review aimed to provide a brief information about the protective effect of natural products against chemotherapy-induced cardiotoxicity Methods: To complete this review, relevant literatures were searched from several scientific databases including Google, Google Scholar, Scopus, Web of Science and Pubmed. Results: In this paper, we have reviewed ten natural products (curcumin, mangiferin, naringenin, quercetin, 6-gingerol, lycopene, resveratrol, apigenin, proanthocyanidins and indole-3-carbinol), which have major influences in attenuating chemotherapy-drug induced cardiotoxicity. Apart from the cardioprotective effects, they tend to confer some synergistic effects with chemotherapeutic agents and therefore have the potential to be used as an adjunct. Conclusion: Though a panel of natural products demonstrate protective effects against cardiotoxicity in cells and animal models, their therapeutic potentials for clinical needs further investigation. [ABSTRACT FROM AUTHOR]

Taxol is one of the anticancer drugs synthesized naturally in the evergreen Taxus brevifolia forest tree belonging to the yew family (Taxaceae) growing on the Pacific. There are reportedly evidence for treating ovarian, breast and lung cancers through this drug given its unique structural and functional features. Extraction of this drug from yew trees bark is one of the most common ways of producing this drug, but 3000 trees are needed to obtain a kilogram of Taxol. Hence, further attention has recently been attracted to the metabolic engineering strategies, including, engineering cellular metabolism of microorganisms and their optimization. Accordingly, the present paper article was aimed to review recent advances in elevating the production and commercialization of Taxol through metabolic engineering techniques. [ABSTRACT FROM AUTHOR]

Background: Histone deacetylases (HDACs) are a class of proteins which catalyze the removal of acetyl groups from lysine residues from both histone and nonhistone proteins, playing a key role in gene transcriptions as well as in all biological processes involving chromatin. Apart from their catalytic activity, HDACs also control other cellular processes such as apoptosis, angiogenesis, or chaperone function. Several classes of HDACs inhibitors have been synthesized and assessed using in silico or in vitro methods. The interest in HDACs inhibitors synthesis is increasing due to their potential anticancer activity. Objective: The study aims to cover relevant published literature from the last years, focusing on the important discoveries of HDAC6 inhibitors. Material and methods: Using PubMed, Wiley, Springer, ScienceDirect, and Reaxys database, we have reviewed the most relevant papers covering HDAC6 inhibitors, as well as some in silico docking studies for different ligands to get the best fit for HDAC6 inhibitors. Results : Before 1996, fewer than 100 papers were published in the field of HDACs. Since then, the number of articles has increased dramatically, with over 10,000 papers published on the topic, including more then 700 papers addressing HDAC6 and their inhibitors by 2023 and 2024. Conclusions: However, despite significant interest for the topic, challenges remain in optimizing their efficacy and minimizing off-target effects. New inhibitors are being designed using rational algorithms and even AI platforms. Nonetheless, the cumulative data from the last 15 years underscore the potential of HDACs as valuable tools in both basic research and clinical applications, emphasizing the need for ongoing exploration and refinement of these compounds for improved therapeutic outcomes.Acknowledgements: This work was supported by the University of Medicine, Pharmacy, Science and Technology "George Emil Palade", Târgu Mureş, Research Grant number 293/14.01.2020 [ABSTRACT FROM AUTHOR]

The aim of this study is to develop 177Lu-5-Flourouracil as a potential cancer therapeutic radiopharmaceutical. 5-Flourouracil (5-FU) is widely accepted as an anticancer drug of broad spectrum fame. The labeling of 5-FU was carried out at different set of experimental conditions using high specific activity of 177LuCl3. The optimum conditions for maximum radiochemical yield was set: 5-FU (5 mg), 177LuCl3 (185 MBq), diethylenetriaminepentaacetic acid (10 µg), reaction volume (2 mL), pH (5.5), temperature (80°C), and reaction time (20 min). The radiochemical labeling was assessed with Whatman No. 2 paper, instant thin layer chromatographic, and radio-HPLC, which revealed >94% labeling results with sufficient stability up to 6 h. Serum stability study also showed 177Lu-5-FU promising stability. Biodistribution study in normal rats and rabbits showed liver, stomach, kidney, and heart as area of increased tracer accumulation just after injection, which decreased to 1.4%, 0.4%, 0.2%, and 0.39% ID/g, respectively, after 72 h. Glomerular filtration rate and cytotoxicity study results of 177Lu-5-FU showed it had no adverse effect on renal function and nontoxic to blood cells. The promising characteristics of 177Lu-5-FU, that is, clever elimination from kidney and nontoxic nature toward blood cells make it the radiopharmaceutical for further testing in patients for therapeutic purposes. [ABSTRACT FROM AUTHOR]

Drug development from medicinal plants constitutes an important strategy for finding natural anticancer therapies. While several plant secondary metabolites with potential antitumor activities have been identified, well-defined mechanisms of action remained uncovered. In fact, studies of medicinal plants have often focused on the genome, transcriptome, and proteome, dismissing the relevance of the metabolome for discovering effective plant-based drugs. Metabolomics has gained huge interest in cancer research as it facilitates the identification of potential anticancer metabolites and uncovers the metabolomic alterations that occur in cancer cells in response to treatment. This holds great promise for investigating the mode of action of target metabolites. Although metabolomics has made significant contributions to drug discovery, research in this area is still ongoing. In this review, we emphasize the significance of plant metabolomics in anticancer research, which continues to be a potential technique for the development of anticancer drugs in spite of all the challenges encountered. As well, we provide insights into the essential elements required for performing effective metabolomics analyses. [ABSTRACT FROM AUTHOR]

CIGB-300 is an antitumor peptide that inhibits the CK2-mediated phosphorylation by direct targeting of substrates. This paper aims to describe breakthroughs about the CIGB-300 antineoplastic mechanism related to the inhibition of CK2-mediated phosphorylation and the synergism with anticancer drugs. CK2 phosphorylation assays were performed with catalytic CK2α subunit or the CK2 holoenzyme in presence or not of CIGB-300. CIGB-300/CK2 interaction was verified by pull-down experiments, in situ colocalization and phosphoproteomic analysis of CIGB-300-treated lung cancer cells were also performed. Synergism of the peptide with anticancer drugs was evaluated in vitro and for Cisplatin; it was also tested in vivo. Besides, comparative proteomics of CIGB-300 combined with Cisplatin was conducted. CIGB-300 targeted the CK2α subunit and inhi-bited the enzymatic activity of the holoenzyme in different experimental settings. Likewise, phosphoproteomic and Western Blot analysis allowed for knowing the early CK2 inhibition profile elicited by CIGB-300 at 10 and 30 min of treatment. Moreover, CIGB-300 did synergize with chemotherapeutics and EGFR inhibitors, and molecular events that reportedly support such synergistic interactions were also known. CIGB-300 inhibits the CK2-mediated phosphorylation by using an alternative mechanism of direct interaction with the enzyme itself. Besides, CIGB-300 synergizes with chemotherapeutics and EGFR inhibitors by modulating different proteins related to drug resistance. [ABSTRACT FROM AUTHOR]

To review the available published data regarding the incidence, mechanisms of pathogenesis, clinical presentations and management of pneumonitis caused by anti-cancer treatments (radiotherapy (RT) and systemic agents) that are included in the guidelines of the treatment of breast cancer (BC) and address the issues on the current grading classification of pneumonitis. A literature search was performed between July and October 2013 using PubMed for papers published from January 1989 to October 2013. Any clinical trial, case report, case series, meta-analysis or systematic review that reported on pulmonary toxicity of any BC therapeutic modality was included (only papers published in English). Most of anticancer treatments currently used in the management of BC may induce some degree of pneumonitis that is estimated to have an incidence of 1-3 %. There is an obvious distinction between chemotherapy- and targeted treatment-related lung toxicity. Moreover, the current classification of pneumonitis needs to be modified as there is a clear diversity in grade 2. As pneumonitis is relatively common and reported as side effect of new anticancer agents, physicians need to be aware of the clinical and radiological manifestations of drug- and RT-induced toxicities in patients with BC. A key recommendation is the subdivision of grade 2 cases to two subgroups. We provide an algorithm, along with real life cases as managed in the breast Unit of Royal Marsden Hospital, with the aim to guide physicians in managing all possible eventualities that may come across in clinical practise. [ABSTRACT FROM AUTHOR]

Conventional pharmaceuticals generally display the inability to transport active ingredients directly to specific regions of the body, amongst some of their main limitations. The distribution of the drugs in the circulatory system may lead to undesired toxicity, and therefore, adverse reactions. To address this situation, a selective transport of drugs is required, that is, releasing drugs specifically to the site of action in appropriate concentrations and in the right time. To achieve this goal, it is necessary to develop delivery systems that respond to several features, such as low toxicity, optimum properties for the transport and release of the drug, as well as a long half-life in the body. This feature paper critically provides an overview of different strategies of controlled drug release for two model antineoplasic drugs, i.e. doxorubicin (DOX) and 5-fluorouracil (5-FU). Any of the presented strategies for drug release possess advantages and disadvantages, and the selection of the strategy used will depend on the targeted tissue and nature of the drug. [ABSTRACT FROM AUTHOR]

Abstract: Matrix metalloproteinase 2 (MMP-2) is a well-known anticancer target belonging to the MMP family. Because of the bilateral role of MMPs in cancer, developing highly selective MMP-2 inhibitors is a current challenge. In this paper, we investigated the binding modes of green tea polyphenols epigallocatechin gallate and epicatechin into the active site of the MMP-2 enzyme. The structure-based analysis allowed the optimization of these hits and hence led to a better lead candidate. Moreover, using a pharmacophore model, we screened FooDB compounds and selected food components as potential MMP-2 inhibitors. The search for food-derived compounds that target this enzyme may represent a strategy to identify new lead molecules with improved safety profiles and provide indications about possible functional foods.Graphical abstract: [ABSTRACT FROM AUTHOR]

This article reports changes to the authorship of two papers by Vinci & Chateigner [(2022). Acta Cryst. B78, 835–841; (2023). Acta Cryst. B79, 213–219], as well as providing additional literature citations. [ABSTRACT FROM AUTHOR]

Globally, cancer is a serious health problem. It is unfortunate that current anti-cancer strategies are insufficiently specific and damage the normal tissues. There's urgent need for development of new anti-cancer strategies. More recently, increasing attention has been paid to the new application of ferroptosis and nano materials in cancer research. Ferroptosis, a condition characterized by excessive reactive oxygen species-induced lipid peroxidation, as a new programmed cell death mode, exists in the process of a number of diseases, including cancers, neurodegenerative disease, cerebral hemorrhage, liver disease, and renal failure. There is growing evidence that inducing ferroptosis has proven to be an effective strategy against a variety of chemo-resistant cancer cells. Nano-drug delivery system based on nanotechnology provides a highly promising platform with the benefits of precise control of drug release and reduced toxicity and side effects. This paper reviews the latest advances of combination therapy strategies based on biomedical nanotechnology induced ferroptosis for cancer therapeutics. Given the new chances and challenges in this emerging area, we need more attention to the combination of nanotechnology and ferroptosis in the treatment of cancer in the future. [Display omitted] • Current anti-cancer strategies are lack of specificity and damage normal tissues. • Ferroptosis is an effective strategy against chemo-resistant cancer cells. • Nanotechnology provides of precise control of drug release and reduced toxicity. • Combination therapy based on ferroptosis-induced nano-DDS brings enhanced antitumor effect and has satisfactory safety. [ABSTRACT FROM AUTHOR]

Simple Summary: Despite recent advances in treatment options, such as chemotherapy, cancer continues to be the second-leading cause of death worldwide. Significant hurdles in the success of chemotherapy regimens include severe adverse effects, as well as drug resistance. As such, there is a strong requirement for novel pharmacological interventions in the treatment of cancer. Natural products, such as monosaccharides, are a promising potential treatment option for cancer due to their low toxicity, high solubility, and high specificity for tumour cells. Several naturally occurring and synthetically modified sugars have displayed toxicity in a variety of cancer and tumour cells. A major hallmark of cancer is the reprogramming of cellular metabolism from oxidative phosphorylation (OXPHOS) to glycolysis, a phenomenon known as the Warburg effect. To sustain high rates of glycolysis, cancer cells overexpress GLUT transporters and glycolytic enzymes, allowing for the enhanced uptake and consumption of glucose. The Warburg effect may be exploited in the treatment of cancer; certain epimers and derivatives of glucose can enter cancer cells and inhibit glycolytic enzymes, stunting metabolism and causing cell death. These include common dietary monosaccharides (ᴅ-mannose, ᴅ-galactose, ᴅ-glucosamine, ʟ-fucose), as well as some rare monosaccharides (xylitol, ᴅ-allose, ʟ-sorbose, ʟ-rhamnose). This article reviews the literature on these sugars in in vitro and in vivo models of cancer, discussing their mechanisms of cytotoxicity. In addition to this, the anticancer potential of some synthetically modified monosaccharides, such as 2-deoxy-ᴅ-glucose and its acetylated and halogenated derivatives, is reviewed. Further, this article reviews how certain monosaccharides can be used in combination with anticancer drugs to potentiate conventional chemotherapies and to help overcome chemoresistance. Finally, the limitations of administering two separate agents, a sugar and a chemotherapeutic drug, are discussed. The potential of the glycoconjugation of classical or repurposed chemotherapy drugs as a solution to these limitations is reviewed. [ABSTRACT FROM AUTHOR]

Glioblastoma (GBM) is a severe form of brain tumor that has a high fatality rate. It grows aggressively and most of the time results in resistance to traditional treatments like chemo- and radiotherapy and surgery. Biodiversity, beyond representing a big resource for human well-being, provides several natural compounds that have shown great potential as anticancer drugs. Many of them are being extensively researched and significantly slow GBM progression by reducing the proliferation rate, migration, and inflammation and also by modulating oxidative stress. Here, the use of some natural compounds, such as Allium lusitanicum, Succisa pratensis, and Dianthus superbus, was explored to tackle GBM; they showed their impact on cell number reduction, which was partially given by cell cycle quiescence. Furthermore, a reduced cell migration ability was reported, accomplished by morphological cytoskeleton changes, which even highlighted a mesenchymal–epithelial transition. Furthermore, metabolic studies showed an induced cell oxidative stress modulation and a massive metabolic rearrangement. Therefore, a new therapeutic option was suggested to overcome the limitations of conventional treatments and thereby improve patient outcomes. [ABSTRACT FROM AUTHOR]

While drug combination therapies are of great importance, particularly in cancer treatment, identifying novel synergistic drug combinations has been a challenging venture. Computational methods have emerged in this context as a promising tool for prioritizing drug combinations for further evaluation, though they have presented limited performance, utility, and interpretability. Here, we propose a novel predictive tool, piscesCSM, that leverages graph-based representations to model small molecule chemical structures to accurately predict drug combinations with favourable anticancer synergistic effects against one or multiple cancer cell lines. Leveraging these insights, we developed a general supervised machine learning model to guide the prediction of anticancer synergistic drug combinations in over 30 cell lines. It achieved an area under the receiver operating characteristic curve (AUROC) of up to 0.89 on independent non-redundant blind tests, outperforming state-of-the-art approaches on both large-scale oncology screening data and an independent test set generated by AstraZeneca (with more than a 16% improvement in predictive accuracy). Moreover, by exploring the interpretability of our approach, we found that simple physicochemical properties and graph-based signatures are predictive of chemotherapy synergism. To provide a simple and integrated platform to rapidly screen potential candidate pairs with favourable synergistic anticancer effects, we made piscesCSM freely available online at https://biosig.lab.uq.edu.au/piscescsm/ as a web server and API. We believe that our predictive tool will provide a valuable resource for optimizing and augmenting combinatorial screening libraries to identify effective and safe synergistic anticancer drug combinations. Scientific contribution: This work proposes piscesCSM, a machine-learning-based framework that relies on well-established graph-based representations of small molecules to identify and provide better predictive accuracy of syngenetic drug combinations. Our model, piscesCSM, shows that combining physiochemical properties with graph-based signatures can outperform current architectures on classification prediction tasks. Furthermore, implementing our tool as a web server offers a user-friendly platform for researchers to screen for potential synergistic drug combinations with favorable anticancer effects against one or multiple cancer cell lines. [ABSTRACT FROM AUTHOR]