In 1980, tamoxifen was introduced as an effective adjuvant endocrine therapy for breast cancer, resulting in a significant increase in overall survival. Nevertheless, the development of acquired resistance limited the efficacy of tamoxifen therapy. Several molecular mechanisms have been proposed to explain the probable process of tamoxifen resistance. In vitro studies have suggested that alterations in the expression of cytoplasmic growth cascades such as insulin-like growth factor receptor (IGFR) and epidermal growth factor receptor (EGFR) along with associated downstream signaling pathways such as ERK1, ERK2, and ERK6 are the main cause of resistance to tamoxifen. In this review, we investigated the role of estrogen receptor-α,(ER-α, ), EGFR, IGFR, and their downstream signaling pathways in tamoxifen resistance. The present study attempted to find out possible culprits of tamoxifen resistance to improve treatment efficacy in breast cancer patients.

Xanthone derivatives, known for their bioactive properties, have garnered significant attention in recent years owing to their potential therapeutic applications. In this study, we isolated three xanthone derivatives, α-mangostin (1), β-mangostin (2), and 2,8-diisoprenyl-1,3-dihydroxy-6,7-dimethoxyxanthone (3), from the ethyl acetate fraction of Garcinia mangostana twigs. Structural identification of these compounds was confirmed by UV, IR, NMR, and MS analyses. Notably, compound 3 was isolated from twigs of G. mangostana for the first time. The inhibitory activity of the isolated compounds was evaluated against several receptor tyrosine kinases (RTKs), including the Epidermal Growth Factor Receptor (EGFR), HER2, HER4, IGFR, InsR, KDR, PDGFRα, and PDGFRβ. Compounds 1-3 exhibited moderate EGFR inhibition, with inhibitory effects ranging from 29-30%. Molecular docking studies revealed that these compounds interacted with EGFR through hydrogen bonding and hydrophobic interactions, with binding energies of -8.4, -8.2, and -8.2 kcal/mol, respectively. This study highlights the potential of xanthone derivatives as selective inhibitors of specific RTKs, offering insights for developing targeted cancer therapies. In particular, the selective activity of compound 2 against EGFR suggests promising therapeutic applications for EGFR-related conditions, including certain cancers and provides a foundation for future research on drug development.