Title:Epidermal Growth Factor Receptor (EGFR) and its Cross-Talks with Topoisomerases: Challenges and Opportunities for Multi-Target Anticancer Drugs
Volume: 22
Issue: 21
Author(s): Monika Chauhan, Gourav Sharma, Gaurav Joshi and Raj Kumar
Affiliation:
Keywords:
Cancer, epidermal growth factor receptor, topoisomerase, crosstalks, anticancer drug discovery.
Abstract: Background: The interactions of Epidermal Growth Factor Receptor (EGFR) and topoisomerases have
been seen in various cancer including brain, breast, ovarian, colorectal, gastric, etc. Methods: The studies in adenocarcinoma
patients, chromogenic in situ hybridization, western blotting, receptor binding assay and electromobility
shift assays, etc. threw light on the biophysical and biochemical features of EGFR and Topoisomerase
cross-talks. Results: It has been revealed that both the isomers of topoisomerase (Topo I and Topo II) interact via
different mechanisms with EGFR. Topo II and HER2 share the same location i.e. 17q12–21 regions which could
be a possible cause of predominant interactions seen between them. Topo I and EGFR interactions are mechanically
related to the nucleolar translocation of heparenase by EGF and c-Jun. Conclusion: We compiled literature
findings including the mechanistic interventions, signaling pathways, patents, in vitro and in vivo data of tested inhibitors
and combinations in clinical trials, which provide convincing confirmations for the interactions of EGFR and topoisomerases.
These interactions may be used for deriving a consistent route of mechanism, design and development of standard drug combinations and
dual or multi inhibitors.
