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Developing anticancer drugs from preclinical to clinical takes approximately a decade in a cutting-edge biomedical lab and still 97% of most fail at clinical trials. Cell line usage is critical in expediting the advancement of anticancer therapies. Yet developing appropriate cell lines has been challenging and overcoming these obstacles whilst implementing a systematic approach of utilizing 3D models that recapitulate the tumour microenvironment is prudent. Using a robust and continuous supply of cell lines representing all ethnic groups from all locales is necessary to capture the evolving tumour landscape in culture. Next, the conversion of these models to systems on a chip that can by way of high throughput cytotoxic assays identify drug leads for clinical trials should fast-track drug development while markedly improving success rates. In this review, we describe the challenges that have hindered the progression of cell line models over seven decades and methods to overcome this. We outline the gaps in breast and prostate cancer cell line pathology and racial representation alongside their involvement in relevant drug development.

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INTRODUCTION: The third-generation of aromatase inhibitors (AIs)-Exemestane (Exe), Letrozole (Let), and Anastrozole (Ana)-is the main therapeutic approach applied for estrogen receptor-positive (ER+) breast cancer (BC), the most common neoplasm in women worldwide. Despite their success, the development of resistance limits their efficacy. Genistein (G), a phytoestrogen present in soybean, has promising anticancer properties in ER+ BC cells, even when combined with anticancer drugs. Thus, the potential beneficial effects of combining G with AIs were investigated in sensitive (MCF7-aro) and resistant (LTEDaro) BC cells. METHODS: The effects on cell proliferation and expression of aromatase, ERα/ERß, and AR receptors were evaluated. RESULTS: Unlike the combination of G with Ana or Let, which negatively affects the Ais' therapeutic efficacy, G enhanced the anticancer properties of the steroidal AI Exe, increasing the antiproliferative effect and apoptosis relative to Exe. The hormone targets studied were not affected by this combination when compared with Exe. CONCLUSIONS: This is the first in vitro study that highlights the potential benefit of G as an adjuvant therapy with Exe, emphasizing, however, that soy derivatives widely used in the diet or applied as auxiliary medicines may increase the risk of adverse interactions with nonsteroidal AIs used in therapy.

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Cancer is one of the main public health problems globally, there is a public demand for better drugs. Rational strategies or approaches are used to improve the success of drug discovery. Our strategy was to the repurposing of well-known antifungal agents as potential anticancer drugs, such as Clotrimazole (CTZ) and Ketoconazole (KTZ). We prepared the respective iodide imidazolium salt L1: (CTZ-Me)I and L2: (KTZ-Me)I to be the intermediates toward the synthesis of its respective NHC ligand and achieve the respective silver(I)-monoNHC and silver(I)-bisNHC derivatives: [Ag(L1)I] (1), [AgI(L2)] (2) [Ag(L1)2]I. (3), [Ag(L2)2]I. (4), as well as their corresponding coordination compounds [Ag(CTZ)2]NO3 (5) and [Ag(KTZ)2]NO3 (6) where these ligands (CTZ and KTZ) coordinate to silver through the N-imidazole atom. These compounds (L1, L2 and complexes 1-6) exhibited significant activity against the tested cancer cell lines (B16-F1, murine melanoma strains and CT26WT, murine colon carcinoma). The silver(I) complexes were more active than the free ligands, complexes 2 and 4 being the most selective in B16-F1 cancer cell line. Two possibles biological targets such as DNA and albumin were examined for the observed anticancer activity. Results show that DNA is not the main target, however, the interactions with albumin suggest it can transport/delivery the metal complexes.

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BACKGROUND: In the last decade, cancer has been a leading cause of death worldwide. Despite the impressive progress in cancer therapy, firsthand treatments are not selective to cancer cells and cause serious toxicity. Thus, the design and development of selective and innovative small molecule drugs is of great interest, particularly through in silico tools. OBJECTIVE: The aim of this review is to analyze different subsections of computer-aided drug design (CADD) in the process of discovering anticancer drugs. METHODS: Articles from the 2008-2021 timeframe were analyzed and based on the relevance of the information and the JCR of its journal of precedence, were selected to be included in this review. RESULTS: The information collected in this study highlights the main traditional and novel CADD approaches used in anticancer drug discovery, its sub-segments, and some applied examples. Throughout this review, the potential use of CADD in drug research and discovery, particularly in the field of oncology, is evident due to the many advantages it presents. CONCLUSION: CADD approaches play a significant role in the drug development process since they allow a better administration of resources with successful results and a promising future market and clinical wise.

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Nature is the largest pharmacy in the world. Doxorubicin (DOX) and paclitaxel (PTX) are two examples of natural-product-derived drugs employed as first-line treatment of various cancer types due to their broad mechanisms of action. These drugs are marketed as conventional and nanotechnology-based formulations, which is quite curious since the research and development (R&D) course of nanoformulations are even more expensive and prone to failure than the conventional ones. Nonetheless, nanosystems are cost-effective and represent both novel and safer dosage forms with fewer side effects due to modification of pharmacokinetic properties and tissue targeting. In addition, nanotechnology-based drugs can contribute to dose modulation, reversion of multidrug resistance, and protection from degradation and early clearance; can influence the mechanism of action; and can enable drug administration by alternative routes and co-encapsulation of multiple active agents for combined chemotherapy. In this review, we discuss the contribution of nanotechnology as an enabling technology taking the clinical use of DOX and PTX as examples. We also present other nanoformulations approved for clinical practice containing different anticancer natural-product-derived drugs.

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The present study investigates the use of UV light and the ozone process for doxorubicin, daunorubicin, epirubicin, and irinotecan degradation. The process was carried out using different pH values in hospital wastewater. The use of UV radiation reduces the concentration of anticancer drugs, but in all cases, this technology was not able enough to remove on the whole these contaminants from hospital wastewater. The best condition was achieved when using pH 9 for most of the analytes. Doxorubicin, daunorubicin, and epirubicin were degraded at 97.3%, 88.3%, and 99.0%, respectively. Irinotecan showed the lowest degradation, just 55.6%; a slightly higher degradation (63.8%) was obtained when pH 5 was used. Complete removal of doxorubicin, daunorubicin, epirubicin, and irinotecan was achieved when ozone treatment was used for all the pH studied. The results indicated that UV light and the ozone process can be used as a tertiary treatment to reduce the concentration of anticancer drugs in the effluents. Ozonation, therefore, proved to be more efficient than the photolysis process, when considering the percentual degradation of the original compounds in shorter timespans.

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Polymersomes are biomimetic cell membrane-like model structures that are self-assembled stepwise from amphiphilic copolymers. These polymeric (nano)carriers have gained the scientific community's attention due to their biocompatibility, versatility, and higher stability than liposomes. Their tunable properties, such as composition, size, shape, and surface functional groups, extend encapsulation possibilities to either hydrophilic or hydrophobic cargoes (or both) and their site-specific delivery. Besides, polymersomes can disassemble in response to different stimuli, including light, for controlling the "on-demand" release of cargo that may also respond to light as photosensitizers and plasmonic nanostructures. Thus, polymersomes can be spatiotemporally stimulated by light of a wide wavelength range, whose exogenous response may activate light-stimulable moieties, enhance the drug efficacy, decrease side effects, and, thus, be broadly employed in photoinduced therapy. This review describes current light-responsive polymersomes evaluated for anticancer therapy. It includes light-activable moieties' features and polymersomes' composition and release behavior, focusing on recent advances and applications in cancer therapy, current trends, and photosensitive polymersomes' perspectives.

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Microorganisms are remarkable producers of a wide diversity of natural products that significantly improve human health and well-being. Currently, these natural products comprise half of all the pharmaceuticals on the market. After the discovery of penicillin by Alexander Fleming 85 years ago, the search for and study of antibiotics began to gain relevance as drugs. Since then, antibiotics have played a valuable role in treating infectious diseases and have saved many human lives. New molecules with anticancer, hypocholesterolemic, and immunosuppressive activity have now been introduced to treat other relevant diseases. Smaller biotechnology companies and academic laboratories generate novel antibiotics and other secondary metabolites that big pharmaceutical companies no longer develop. The purpose of this review is to illustrate some of the recent developments and to show the potential that some modern technologies like metagenomics and genome mining offer for the discovery and development of new molecules, with different functions like therapeutic alternatives needed to overcome current severe problems, such as the SARS-CoV-2 pandemic, antibiotic resistance, and other emerging diseases. KEY POINTS: • Novel alternatives for the treatment of infections caused by bacteria, fungi, and viruses. • Second wave of efforts of microbial origin against SARS-CoV-2 and related variants. • Microbial drugs used in clinical practice as hypocholesterolemic agents, immunosuppressants, and anticancer therapy.

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Colorectal cancer (CRC) ranks second in the number of cancer deaths worldwide, mainly due to late diagnoses, which restrict treatment in the potentially curable stages and decrease patient survival. The treatment of CRC involves surgery to remove the tumor tissue, in addition to radiotherapy and systemic chemotherapy sessions. However, almost half of patients are resistant to these treatments, especially in metastatic cases, where the 5-year survival rate is only 12%. This factor may be related to the intratumoral heterogeneity, tumor microenvironment (TME), and the presence of cancer stem cells (CSCs), which is impossible to resolve with the standard approaches currently available in clinical practice. CSCs are APC-deficient, and the search for alternative therapeutic agents such as small molecules from natural sources is a promising strategy, as these substances have several antitumor properties. Many of those interfere with the regulation of signaling pathways at the central core of CRC development, such as the Wnt/ß-catenin, which plays a crucial role in the cell proliferation and stemness in the tumor. This review will discuss the use of naturally occurring small molecules inhibiting the Wnt/ß-catenin pathway in experimental CRC models over the past decade, highlighting the molecular targets in the Wnt/ß-catenin pathway and the mechanisms through which these molecules perform their antitumor activities.