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Epidermal Growth Factor Receptor (EGFR) and its Cross-Talks with Topoisomerases: Challenges and Opportunities for

Monika Chauhan, Gourav Sharma, Gaurav Joshi

  • 1Centre for Pharmaceutical Sciences and Natural Products, School of Basic and Applied Sciences, Central University of Punjab, Bathinda 151 001, India. raj.khunger@gmail.com.

Current Pharmaceutical Design
|February 25, 2016
PubMed
Abstract

Insights

Epidermal Growth Factor Receptor (EGFR) and topoisomerase interactions are implicated in many cancers. Understanding these cross-talks informs new therapeutic strategies and drug development.

Area of Science:

  • Oncology
  • Molecular Biology
  • Biochemistry

Background:

  • Epidermal Growth Factor Receptor (EGFR) and topoisomerase interactions are observed across diverse cancers, including brain, breast, ovarian, colorectal, and gastric malignancies.
  • These interactions play a significant role in cancer progression and development.

Purpose of the Study:

  • To elucidate the biophysical and biochemical mechanisms underlying the cross-talk between EGFR and topoisomerases.
  • To compile and analyze existing literature on these interactions for therapeutic implications.

Main Methods:

  • Literature review of mechanistic interventions, signaling pathways, and preclinical/clinical data.
  • Analysis of in vitro and in vivo studies on inhibitors and drug combinations.
  • Examination of patents related to EGFR and topoisomerase interactions.

Main Results:

  • Both Topoisomerase I (Topo I) and Topoisomerase II (Topo II) isomers interact with EGFR through distinct mechanisms.
  • Topo II and HER2 share chromosomal region 17q12-21, potentially explaining their frequent interactions.
  • Topo I interactions with EGFR are linked to EGF- and c-Jun-mediated nucleolar translocation of heparanase.

Conclusions:

  • Confirmed interactions between EGFR and topoisomerases through compiled literature findings.
  • These interactions provide a basis for developing targeted therapies, including dual or multi-target inhibitors and standard drug combinations.
  • Further research into these mechanisms can guide the design of novel anti-cancer drugs.

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