AcGlcAs: A Novel P53-Targeting Arsenical with Potent Cellular Uptake and Cancer Cell Selectivity.

Arsenic trioxide (ATO) targets PML/RARα and leads to miraculous success in treating acute promyelocytic leukemia. Notably, ATO also targets p53, the most frequently mutated protein in cancers, through a similar binding mechanism. However, p53-targeting ATO trials are challenging due to the poor cellular uptake and cancer selectivity of ATO.

Discovery of MAO-B Inhibitor with Machine Learning, Topomer CoMFA, Molecular Docking and Multi-Spectroscopy Approaches.

Alzheimer's disease (AD) is the most common type of dementia and is a serious disruption to normal life. Monoamine oxidase-B (MAO-B) is an important target for the treatment of AD. In this study, machine learning approaches were applied to investigate the identification model of MAO-B inhibitors.

Carbohydrate-based drugs launched during 20002021.

Carbohydrates are fundamental molecules involved in nearly all aspects of lives, such as being involved in formating the genetic and energy materials, supporting the structure of organisms, constituting invasion and host defense systems, and forming antibiotics secondary metabolites. The naturally occurring carbohydrates and their derivatives have been extensively studied as therapeutic agents for the treatment of various diseases. During 2000 to 2021, totally 54 carbohydrate-based drugs which contain carbohydrate moities as the major structural units have been approved as drugs or diagnostic agents.

Synthetic Retinoid Kills Drug-Resistant Cancer Stem Cells via Inducing RARγ-Translocation-Mediated Tension Reduction and Chromatin Decondensation.

A recently developed synthetic retinoid abrogates proliferation and induces apoptosis of drug-resistant malignant-cancer-stem-cell-like cells. However, the underlying mechanisms of how the synthetic retinoid induces cancer-stem-cell-like cell tumor-repopulating cell (TRC) apoptosis are elusive. Here, it is shown that although the retinoid and conventional anticancer drugs cisplatin, all-trans retinoic acid, and tazarotene all inhibit cytoskeletal tension and decondense chromatin prior to inducing TRC apoptosis, half-maximal inhibitory concentration of the retinoid is 20-fold lower than those anticancer drugs.

Acquired resistance to third-generation EGFR-TKIs and emerging next-generation EGFR inhibitors.

The discovery that mutations in the gene are detected in up to 50% of lung adenocarcinoma patients, along with the development of highly efficacious epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs), has revolutionized the treatment of this frequently occurring lung malignancy. Indeed, the clinical success of these TKIs constitutes a critical milestone in targeted cancer therapy. Three generations of EGFR-TKIs are currently approved for the treatment of EGFR mutation-positive non-small cell lung cancer (NSCLC).

Sulfarotene, a synthetic retinoid, overcomes stemness and sorafenib resistance of hepatocellular carcinoma via suppressing SOS2-RAS pathway.

Background: Recurrent hepatocellular carcinoma (HCC) shows strong resistance to sorafenib, and the tumor-repopulating cells (TRCs) with cancer stem cell-like properties are considered a driver for its high recurrent rate and drug resistance.

Methods: Suppression of TRCs may thus be an effective therapeutic strategy for treating this fatal disease. We evaluated the pharmacology and mechanism of sulfarotene, a new type of synthetic retinoid, on the cancer stem cell-like properties of HCC TRCs, and assessed its preclinical efficacy in models of HCC patient-derived xenografts (PDXs).

Role of miR-221/222 in Tumor Development and the Underlying Mechanism.

MicroRNA-221/222 (miRNA-221/222, miR-221/222) is a noncoding microRNA which is widely distributed in eukaryotic organisms and deeply involved in the posttranscriptional regulation of gene expressions. According to recent studies, abnormal expressions of miR-221/222 are closely related to the occurrence and development of various kinds of malignant tumors. The role of miR-221/222 in tumor development and their potential molecular mechanism in various cancers, including liver cancer, colorectal cancer, cervical cancer, ovarian cancer, and endometrial carcinoma, are summarized and reviewed in this paper.

Towards the overcoming of anticancer drug resistance mediated by p53 mutations.

Cancer continues to be a leading threat to human health and life. Resistance to anti-cancer drugs is a major impediment towards efficacious cancer treatment. p53 mutations play an important role in cancer cell resistance to chemotherapeutic drugs.

Inhibition of cancer stem cell like cells by a synthetic retinoid.

Developing novel drugs that can abrogate the growth and metastasis of malignant tumors is a major challenge for cancer researchers. Here we describe a novel synthetic retinoid, namely WYC-209, which inhibits proliferation of malignant murine melanoma tumor-repopulating cells (TRCs), known to resist conventional drug treatment, with an IC of 0.19 μM in a dose-dependent manner.