The EMT spectrum and therapeutic opportunities

Area of Science:

• Oncology
• Molecular Biology
• Epigenetics

Background:

• Carcinomas exhibit phenotypic plasticity along an epithelial-mesenchymal transition (EMT) spectrum.
• EMT is implicated in the acquisition of chemoresistance through altered growth factor signaling pathways.
• Epigenetic mechanisms are increasingly recognized as key mediators linking EMT and drug resistance.

Purpose of the Study:

• To review current therapeutic strategies targeting cancer-associated EMT.
• To assess the strengths and weaknesses of existing anti-EMT approaches.
• To propose a novel therapeutic strategy focused on epigenetic reprogramming.

Main Methods:

• Literature review of current therapeutic approaches against cancer-associated EMT.
• Analysis of the relationship between EMT, chemoresistance, and epigenetic mechanisms.
• Hypothesis generation based on the comparison of EMT and cellular reprogramming pathways.

Main Results:

• EMT is closely linked to chemoresistance, particularly concerning targeted therapeutics.
• Epigenetic mechanisms play a crucial role in connecting EMT and drug resistance.
• Carcinoma-associated EMT shares epigenetic pathways with cellular plasticity observed in tissue repair.

Conclusions:

• EMT in carcinoma represents a pathological adaptation of the intrinsic cellular plasticity program essential for tissue homeostasis.
• Targeting the epigenetic mechanisms underlying pathogenic EMT could provide a universal therapeutic approach to arrest cellular plasticity.
• This revised strategy aims to be independent of specific upstream cancer-driving mutations.