Clinical implication intra-tumor heterogeneity
4 important questions on Clinical implication intra-tumor heterogeneity
Where are tumors resistant agains therapy?
- Chemotherapy
- Differentiation therapy - Retinoic acid
Which cells of the neuroblastoma are therapy-resistant?
- MES cells survive therapy better than ADRN
- MES cells - resistant to Retinoic acid (can be checked with marker PRRX1 presence)
Minimal residual disease (MRD) - monitoring
- MDR-markers are mainly expressed in ADRN cells
- MES cells hardly express these ADRN MRD markers
- MES cells may escape detection
- Tumor specific DNA translocation provide alternative MRD-markers
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How to develop new therapies?
- Also two cell types with different epigenetic regulation
- Combination of BM1 and EZH2 inhibition therapy cleared 100% of tumor cells in vitro and almost completely in vivo
Different drug with different marker for a specific cancer cell type line cure the tumor best! Eliminates both cell types
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