Glycan-based scaffolds and nanoparticles as drug delivery system in cancer therapy.

Glycan-based scaffolds are unique in their high specificity, versatility, low immunogenicity, and ability to mimic natural carbohydrates, making them attractive candidates for use in cancer treatment. These scaffolds are made up of glycans, which are biopolymers with well biocompatibility in the human body that can be used for drug delivery. The versatility of glycan-based scaffolds allows for the modulation of drug activity and targeted delivery to specific cells or tissues, which increases the potency of drugs and reduces side effects. Despite their promise, there are still technical challenges in the design and production of glycan-based scaffolds, as well as limitations in their therapeutic efficacy and specificity.

A real-world pharmacovigilance study of amivantamab-related cardiovascular adverse events based on the FDA adverse event reporting system (FAERS) database.

Amivantamab is the first dual-specificity antibody targeting EGFR and MET, which is approved for the treatment of locally advanced or metastatic non-small cell lung cancer (NSCLC) with EGFR exon 20 insertion mutations. Cardiovascular toxicities related to amivantamab have not been reported in the CHRYSALIS study. However, the occurrence of cardiovascular events in the real world is unknown. To comprehensively investigate the clinical characteristics, onset times, and outcomes of cardiovascular toxicities associated with amivantamab. The Food and Drug Administration Adverse Event Reporting System (FAERS) database from 1st quarter of 2019 to the 2nd quarter of 2023 was retrospectively queried to extract reports of cardiovascular adverse events (AEs) associated with amivantamab. To perform disproportionality analysis, the reporting odds ratios (RORs) and information components (ICs) were calculated with statistical shrinkage trans-formation formulas and a lower limit of the 95% confidence interval (CI) for ROR (ROR025) > 1 or IC (IC025) > 0 with at least 3 reports was considered statistically significant. A total of 20,270,918 eligible records were identified, among which 98 records were related to cardiovascular events associated with amivantamab. 4 categories of cardiovascular events exhibited positive signals: venous thrombotic diseases, abnormal blood pressure, arrhythmia, and pericardial effusion. Venous thrombotic diseases and abnormal blood pressure were the two most common signals. The median time to onset (TTO) for cardiovascular AEs was 33 days. The cumulative incidence within 90 days was 100% for cardiac failure, 75% for stroke, 63.16% for arrhythmia, 50% for sudden death, and 44.18% for venous thrombotic diseases. Death accounted for 16.3% of all cardiovascular AEs associated with amivantamab. The mortality rates for Major Adverse Cardiovascular Events (MACE) were up to 60%. This pharmacovigilance study systematically explored the cardiovascular adverse events of amivantamab and provided new safety signals based on past safety information. Early and intensified monitoring is crucial, and attention should be directed towards high-risk signals.

Literature review Analysis of the Current State of Targeted Therapy for Gastrointestinal Cancers.

Globally, more than one million new cases of gastric cancer are anticipated by 2024, representing a significant unmet clinical need. It is the fourth most prevalent cancer in men and the seventh most prevalent cancer in women. The pathogens Helicobacter pylori (H. pylori) and Epstein-Barr virus (EBV) have been linked to a significant number of cases of gastric cancer. On the other hand, the recorded results were not particularly impressive because the gastrointestinal tract (GI) is frequently diagnosed at a very advanced stage, traditional treatments are not very effective, and they have several adverse side effects. In the pursuit of improved systemic therapy, the use of targeted medications has greatly benefited GI care. Immunotherapies, vascular endothelial growth factor, epidermal growth factor receptor, and human epidermal growth factor receptor-2 obstruct the programmed death receptor 1/programmed death-ligand 1 pathway. Advanced gastrointestinal tract (GI) malignancies are increasingly treated at the molecular level. Extended gene RAS and BRAF testing were required to predict the efficacy of trastuzumab (HER2-targeted therapy) and pembrolizumab (anti-PD-1 therapy) for metastatic gastroesophageal (GEJ) malignancies. For metastatic colorectal malignancies, extensive RAS and BRAF testing is required to predict the efficacy of EGFR-targeted therapies. Mismatch repair (MMR) or microsatellite instability (MSI) testing must be performed on all advanced gastrointestinal (GI) malignancies to determine if pembrolizumab or nivolumab with or without ipilimumab will be effective. These advanced tumors are treated with targeted drugs for GI malignancies, and it is now common knowledge that patients must be identified through routine molecular profiling. This article provided a clinical summary of the most recent advances in targeted treatment for GEC and the supporting clinical data, such as their efficacy and safety profiles.

RIOK3 promotes mTORC1 activation by facilitating SLC7A2-mediated arginine uptake in pancreatic ductal adenocarcinoma.

Pancreatic ductal adenocarcinoma (PDAC) is a highly aggressive malignancy with a poor prognosis. Reprogramming of amino acid metabolism is one of the characteristics of PDAC, in which arginine metabolism is significantly altered in PDAC cells and is involved in important signaling pathways. Current studies have identified arginine deprivation as a potential strategy for PDAC treatment. In this study, we performed Liquid Chromatograph Mass Spectrometer (LC-MS)-based non-targeted metabolomic analysis on PDAC cell lines with stable Rio Kinase 3 (RIOK3) knockdown and PDAC tissues with different RIOK3 expressions and found that RIOK3 expression was significantly correlated with arginine metabolism in PDAC. Subsequent RNA sequencing (RNA-Seq) and Western blot analysis showed that RIOK3 knockdown significantly inhibited the expression of arginine transporter solute carrier family 7 member 2 (SLC7A2). Further studies revealed that RIOK3 promoted arginine uptake, mechanistic target of rapamycin complex 1 (mTORC1) activation, cell invasion, and metastasis in PDAC cells via SLC7A2. Finally, we found that patients with high expression of both RIOK3 and infiltrating Treg cells had a worse prognosis. Overall, our study found that RIOK3 in PDAC cells promotes arginine uptake and mTORC1 activation through upregulation of SLC7A2 expression, and also provides a new therapeutic target for therapeutic strategies targeting arginine metabolism.