Metastasis of extragenital malignancies to the female genital tract, particularly the uterus, is exceedingly rare. Invasive lobular carcinoma (ILC) is the most common histological type of breast carcinoma that metastasizes to gynecologic organs.

Although current treatment strategies for nasopharyngeal carcinoma (NPC) have improved, the prognosis for a subset of patients remains poor, largely due to distant metastasis. Resistance to cisplatin is one of the key factors contributing to this unfavorable clinical outcome. This study investigated whether human umbilical cord mesenchymal stem cells-derived exosomes (hUC MSC-Exos) exhibit intrinsic anticancer activity and whether they can enhance the cytotoxic effects of cisplatin in NPC cells.

Oral cancer is a major global public health concern. Despite advancements in treatment, the 5-year survival rate for patients with oral cancer remains low. Developing new therapies or drugs is essential for improving patient outcomes. This study aimed to evaluate the anticancer effects of bis-type triaziquone (BTZQ), a synthesized chemical compound, in an oral cancer cell line.

Failure of radiotherapy is a major factor leading to poor prognosis in colorectal cancer. This study investigated the anticancer effects of a novel curcumin derivative, 4,4-diallyl curcumin bis(2,2-hydroxymethyl)propanoate (35e), on radio-resistant colorectal cancer cells (HT29/RR).

This study aims to elucidate whether Macranthoside B (MB) intensifies paclitaxel (PTX)-induced apoptosis in human cervical adenocarcinoma HeLa cells as well as the underlying mechanisms.

Despite advances in cancer therapy, the incidence and death rates of patients with colorectal cancer are still high, underscoring the need for new treatment strategies. Damnacanthal, an anthraquinone found in Morinda citrifolia L. (common name noni), is known to induce apoptosis and inhibit cell growth in various types of cancer cells. This study aimed to elucidate the anticancer mechanism of damnacanthal in colorectal cancer.

Doxorubicin (DOX) is the most impactful drug developed for osteosarcoma. However, despite its therapeutic effects, it also causes serious side effects, such as cardiotoxicity and hemotoxicity. To address this, we developed a novel DOX prodrug that exhibits high antitumor activity specifically in hypoxic regions while demonstrating low toxicity in normal organs. Based on these properties, we evaluated its efficacy against osteosarcoma with the aim of significantly reducing side effects while maintaining therapeutic efficacy.

Enzymatic anticancer therapies are actively investigated as they can selectively deprive cancer cells of essential nutrients. L-lysine-α-oxidases of different origins have been reported as potential anticancer enzymes with a significant antitumor potency. This study aimed to evaluate the cytotoxic and antitumor activity of L-lysine-α-oxidase obtained from the domestic strain of Trichoderma harzianum Rifai VKPM F-180.

Osteosarcoma is a primary malignant bone tumor with poor prognosis due to frequent metastasis and limited response to standard therapies.

The epithelial-to-mesenchymal transition (EMT) plays an essential role in lung cancer metastasis. This study aimed to explore the EMT inhibitory effect of the new compound 6,6'-(butylazanediyl) bis (methylene) bis (2,4-dimethylphenol) (2,4-diMBD).

Cordyceps militaris, a medicinal fungus, is renowned for its anticancer properties. To maximize its therapeutic efficacy, this study aimed to optimize the extraction and preparation methods of Cordyceps militaris and evaluate its effects on non-small cell lung cancer (NSCLC). Additionally, the study explored the potential of natural products as novel therapeutic agents.

Acute myeloid leukemia (AML) is an aggressive hematologic malignancy. Hsp90 inhibitors, like SNX-2112, are promising anti-cancer agents. However, SNX-2112's clinical use is limited by poor solubility and side effects. This study aimed to improve tetrahydroindazolone-substituted benzamide compounds and to investigate its mechanism of action against AML cells.

Drug-related problems (DRPs) associated with oral anticancer drugs are frequent and require a new healthcare organisation to manage them on an outpatient basis. The aim of this article is to present the study protocol of the Drug Related problems in Oncology Practice (DROP) randomised controlled trial (RCT), endorsed by the French Society for Oncology Pharmacy. The main objective of the DROP RCT is to measure the impact at 6 months of the DROP community/hospital pharmaceutical intervention programme, compared with usual treatment, on the mean number of DRP (ie, adverse effects, drug-drug interactions, medication errors) related to oral anticancer drugs in at-risk outpatients.

Emergence of resistance in acute monocytic leukemia cells (AMoL, AML-M5) to the action of antitumor agents is one of the main reasons for the extremely low survival and curability of the patients diagnosed with AMoL. It is well known that the AML cells have an "inflammatory" phenotype and form a unique pro-inflammatory microenvironment. Previously, we identified increase in the resistance of the THP-1 human AML-M5 cells to the action of DNA topoisomerase I and II inhibitors (topotecan, etoposide, doxorubicin) in the in vitro model simulating conditions of pro-inflammatory microenvironment - a three-dimensional long-term high-density cell culture. In this research, we investigated the mechanisms of this phenomenon using fluorescence microscopy and spectrophotometry, DNA comet assay, Western blot analysis, differential gene expression analysis, and flow cytometry. The results showed that the increase in resistance to the action of DNA topoisomerase inhibitors, in particular etoposide, in the THP-1 AML-M5 cells in a hypercellular proinflammatory microenvironment is realized through reduced accumulation of the single- and double-strand DNA breaks and, accordingly, reduced response to DNA damage. It may also be due to the pronounced activation of the signaling pathways of interferon types 1 and 2, NF-κB/STAT-dependent signaling pathways, occurring against the background of a significant suppression of the activity of transcription factors of the Myc and E2F families. The results of this work provide new ideas about the role of pro-inflammatory activation in the increased resistance of AML cells to the death induced by the action of DNA topoisomerase inhibitors.

Despite recent advances, the regulation of anticancer and antimicrobial bioactive compound (AABC) production by leukocytes remains poorly understood. Here, we demonstrate that inactivation of the DNA- and RNA-based Teazeled receptors of the Universal Receptive System in human leukocytes generated so called "Leukocyte-Tells," which showed enhanced AABC production. Comprehensive analysis of the AABCs produced by Leukocyte-Tells based on LC/MS identified 707 unique or differentially produced peptide or nonpeptide metabolites. Functional testing demonstrated that many of these metabolites exhibited increased antibacterial, antifungal, and anticancer activities. The AABCs produced by the Leukocyte-Tells were effective against different multidrug-resistant clinical isolates of fungi and gram-positive and gram-negative bacteria (including their biofilms), as well as various cancer cell lines, with >100,000-fold activity than AABCs derived from control leukocytes. Notably, the AABCs produced by the Leukocyte-Tells exhibited greater stability under adverse environmental conditions. Our findings highlight the important role of the Universal Receptive System in regulating AABC production through a process named here as cell genome-memory management, offering new insights into immune functions and suggesting potential therapeutic applications.

Histone lysine-specific demethylase 5B (KDM5B) is frequently overexpressed in a wide range of tumors and is regarded as a promising target for drug development. Current drugs targeting KDM5B are primarily small-molecule inhibitors, which suffer from limitations such as poor selectivity and insufficient pharmacological efficacy. Targeted protein degradation (TPD) technology as an emerging drug development strategy has received extensive attention in recent years, that enables the catalytic elimination of the entire protein of interest, thereby disrupting both the enzymatic and non-enzymatic functions. Herein, we investigated a series of novel KDM5B degraders by tethering the KDM5B inhibitor GSK467 to various recruiters that tried to mediate protein degradation via the ubiquitin-proteasome or autophagy-lysosome pathway. Among these, the representative compound YTHu78 effectively induced KDM5B degradation through the ubiquitin-proteasome system and triggered lytic apoptosis in MV-4-11 and MM.1S cell lines. Moreover, YTHu78 demonstrated notable antiproliferative activities against several hematologic malignancy cell lines. In contrast, the KDM5B inhibitor GSK467 neither showed antiproliferative activities in the tested hematologic malignancy cell lines nor induced cell apoptosis. These findings underscore the distinct biological functional differences between the KDM5B degrader and inhibitor. YTHu78 serves as a valuable chemical tool for further exploration of KDM5B's biological roles, and the development of KDM5B-targeted degraders may represent a promising therapeutic strategy for hematologic malignancies in the future.

A series of novel 2,4-diarylaminopyrimidine derivatives incorporating a 3-sulfamoylbenzamide moiety were designed and synthesized as potent focal adhesion kinase (FAK) inhibitors. Three compounds (5f, 10b, and 10c) demonstrated FAK inhibitory activities comparable to the reference inhibitor TAE226. In cellular assays, most analogues exhibited significant antiproliferative effects against four FAK-overexpressing tumor cell lines (HCT116, HeLa, MDA-MB-231, and A375), with IC50 values below 1 μM. Notably, compound 10c displayed superior potency, showing IC50 values ranging from 0.08 to 0.31 μM across the tested cell lines, and exhibited approximately 2-fold enhanced activity over TAE226 in inhibiting HCT116, MDA-MB-231, and A375 cell proliferation. Further mechanistic studies revealed that 10c effectively suppressed colony formation, migration, and adhesion of HCT116 cells, while inducing apoptosis via ROS elevation. Molecular docking analysis suggested that the enhanced activity of 10c may arise from an additional hydrogen bond interaction with the Arg426 residue of FAK, leading to stronger binding affinity compared to TAE226. In vivo, 10c showed good oral bioavailability and significantly inhibited HCT116 xenograft tumor growth (TGI = 62.22 % at 50 mg/kg), outperforming TAE226 (50.98 %) without inducing weight loss or hepatorenal toxicity. These results highlight 10c as a promising FAK-targeted candidate worthy of further preclinical investigation.

Fms-like tyrosine kinase 3 (FLT3) is a type III receptor tyrosine kinase expressed in hematopoietic progenitor cells and in most AML cell lines. Pharmacological inhibition of FLT3 enzymatic function is now a well-established strategy for the treatment of patients with these malignancies. Herein, we report the discovery and characterization of a FLT3 degrader A2. By design, A2 also mediates the degradation of transcription factors GSPT1 and IKZF1/3 through molecular glue interactions with the cereblon E3 ubiquitin ligase complex. Importantly, A2 exhibited significantly enhanced antiproliferative activity against drug-resistant AML cells compared to Gilteritinib (MV-4-11: IC50 = 1.67 ± 0.14 nM vs IC50 = 6.52 ± 1.20 nM). Furthermore, A2 with the rigid linker demonstrated improved some pharmacokinetic properties such as half-life (T1/2), which were achieved through rational design. Overall, A2 achieves concurrent degradation of these proteins by functioning as both PROTAC and molecular glue.

A new series of ortho-phenolic Mannich ciprofloxacin-chalcone hybrids 5a-j were synthesized and evaluated against the NCI-60 cancer cell lines, unveiling their promising potential as cytotoxic agents. Notably, compounds 5a, 5d and 5j exhibited notable anti-proliferative efficacy against both LOX IMVI and HCT 116 cell lines, indicating promising cytotoxic potential, with IC50 = 2.53, 2.01, 17.36, 12.23 and 3.1 μM for HCT-116 cells, respectively and IC50 = 0.73, 0.64, 3.32, 13.72 and 1.17 μM for leukemia SR cells, respectively. Mannich base 5j achieved excellent inhibitory effect on Topo IIβ in both LOX IMVI and HCT-116 cell lines with inhibition value of 75.51 % and 76.39 %. Cell cycle analysis and expression analysis of Bax, Bcl2, P53 and P21 genes were performed on LOX IMVI and HCT-116 cell lines with compound 5j and also on caspase 3 actifundation in HCT-116 and LOX- IMIV cell lines. The docking outcomes aligned with the biological screening revealed higher affinity of the most active compound 5j against topoisomerase-I and topoisomerase-II biotargets, serving it as promising antineoplastic agent. Besides, using atomistic standard 100 ns dynamic simulation consideration, the stability of the formed complexes between compound 5j and the topoisomerase-1 and topoisomerase-2 active sites was considered under dynamic behavior. Hence, Mannich base 5j is considered a promising antineoplastic candidate that requires further in vivo investigation.

A small library of novel potential multi-kinase inhibitors was designed by integrating structure- and ligand-based design approaches through terms of hybridization and fragment-based design tools. The required key pharmacophoric features for the individual kinases' inhibition were fused to achieve the desired inhibitory activity against PI3Kα and CDK2, relying on our previously studied strategy of the structure- and ligand-based design approaches' expansion. Thus, all the synthesized compounds were evaluated for their inhibitory activity against PI3Kα and CDK2/cyclin A2, in addition to CDK8/cyclin C. The newly synthesized compounds exhibited a promising activity at sub-micromolar concentrations toward the three enzymes, indicating the efficacy of the adopted strategies utilized in the current design. Additionally, all the new derivatives were evaluated for their antiproliferative activity at 10 μM against the full NCI-60 cell panel. Compounds 3d, 10b and 11e revealed the highest mean growth inhibition (78.10, 67.41and 73.22 %, respectively). Compounds 3d, 10b and 11e were selected for five-dose assay, where the results indicated higher activity against leukemia (MG-MID = 2.87, 2.65 and 2.74 μM, respectively), and breast cancer (MG-MID = 3.79, 3.29 and 3.34 μM, respectively). Compound 10b displayed a potential activity against Leukemia SR cell line with GI50 of 0.47 μM. In vitro normal Vero cell line cytotoxicity was conducted as well indicating non-significant cytotoxic effect. Modeling studies were achieved for the newly synthesized compounds within the crystal structures of PI3Kα and CDK2, along with CDK8, which augment the biological screening and insightfully validated the utilized design approach.