Oligometastases: Characterizing the Role of Epigenetic Regulation of Epithelial-Mesenchymal Transition.
Rohan R KatipallySean P PitrodaRalph R WeichselbaumSamuel HellmanPublished in: Clinical cancer research : an official journal of the American Association for Cancer Research (2023)
The "oligometastasis" hypothesis proposes that metastases exist as a spectrum and are not always disseminated. According to this theory, a subset of patients with metastatic disease could benefit from aggressive local therapies. However, the identification of patients most likely to exhibit an oligometastatic phenotype remains challenging. Recent literature focusing on basic and translational studies has identified novel epigenetic regulators of epithelial-mesenchymal transition and the emergence of a spectrum of metastatic behavior. Herein, we review these scientific advances and suggest that the spectrum of metastatic virulence produced by these epigenetic mechanisms broadly contributes to the emergence of clinically evident "oligometastases". Epigenetic regulation of epithelial-mesenchymal transition programs can result in a spectrum of cell trajectories (e.g. quasi-mesenchymal and highly mesenchymal states) with differential propensity to develop metastases. We propose that quasi-mesenchymal cell states may be associated with a polymetastatic phenotype, while highly mesenchymal cell states may be associated with a more oligometastatic phenotype. The mechanisms governing epigenetic regulation of epithelial-mesenchymal transition and its array of intermediate states are multifaceted and may contribute to the development of the metastatic spectrum observed clinically. Within this context, translational studies that support the role of epithelial-mesenchymal transition and its epigenetic regulation are discussed. Continued translation of these mechanistic discoveries into novel biomarkers may help optimally select patients most likely to exhibit an oligometastatic phenotype and benefit from aggressive local therapies, such as surgery, radiotherapy, and other ablative procedures.
Keyphrases
- epithelial mesenchymal transition
- transforming growth factor
- end stage renal disease
- squamous cell carcinoma
- signaling pathway
- stem cells
- small cell lung cancer
- bone marrow
- ejection fraction
- single cell
- chronic kidney disease
- systematic review
- gene expression
- cell therapy
- staphylococcus aureus
- peritoneal dialysis
- public health
- coronary artery disease
- acute coronary syndrome
- patient reported outcomes
- pseudomonas aeruginosa
- antimicrobial resistance
- early stage
- biofilm formation
- high resolution
- rectal cancer
- atrial fibrillation
- coronary artery bypass