Molecular mechanisms underpinning sarcomas and implications for current and future therapy

Area of Science:

• Oncology
• Molecular Biology
• Cancer Research

Background:

• Sarcomas are heterogeneous mesenchymal neoplasms with poor prognoses and challenging clinical management.
• Current understanding of sarcoma molecular mechanisms and cell of origin is limited, though mesenchymal stromal/stem cells (MSCs) are implicated.
• Existing treatments are often ineffective due to sarcoma heterogeneity and insensitivity.

Purpose of the Study:

• To provide a comprehensive overview of sarcomagenesis molecular mechanisms.
• To explore the role of mesenchymal stromal/stem cells (MSCs) in modeling sarcomagenesis.
• To review novel aspects like EMT/MET plasticity, exosomes, and microRNAs in sarcoma development and discuss targeted therapeutic strategies.

Main Methods:

• Review of current literature on sarcomagenesis.
• Analysis of mesenchymal stromal/stem cell (MSC) models for in vitro and in vivo sarcomagenesis studies.
• Examination of pre-clinical and clinical studies on targeted sarcoma therapies.

Main Results:

• Sarcomagenesis involves complex molecular mechanisms, potentially unique to each subtype, with increasing evidence pointing to mesenchymal stromal/stem cells (MSCs) as cells of origin.
• Epithelial-to-mesenchymal-transition (EMT)/mesenchymal-to-epithelial-transition (MET) plasticity, exosomes, and microRNAs play significant roles in sarcomagenesis.
• Novel molecular pathways and key transcription factors are being identified for targeted therapy.

Conclusions:

• Understanding the molecular underpinnings of sarcomagenesis, particularly the role of MSCs and associated factors like EMT/MET, exosomes, and microRNAs, is crucial for developing effective targeted therapies.
• Recapitulating sarcomagenesis using MSC models aids in identifying novel therapeutic targets.
• Future research should focus on these molecular pathways and transcription factors to advance targeted sarcoma treatment options.