One of the key areas of cancer research today is understanding how tumors suppress the immune response. In a recent study published in Cell Reports researchers have now identified one of the central players driving this mechanism: the DNMT3A gene. They showed that overexpression of DNMT3A downregulates various genes on monocytes turning these cells into so called Myeloid-Derived Suppressor Cells (MDSC) instead of dendritic cells.
This research is an important step forward in finding therapies that use body’s immune system to identify and attack tumors. An important question therefore is, to what extent DNMT3A could be a suitable target. Using Euretos Search, 57 differential expression experiments for DNMT3A found. All these appear to be in the area of cancer related research reinforcing the potential of DNMT3A as a specific target for neoplastic disorders.
Figure 1: Differential experiments for DNMT3A (source: Euretos Knowledge Platform)
Although the potential of DNMT3A especially in neoplastic disorders is very promising, it is very broadly expressed in all tissues, raising the risk of side effects if targeted:
Figure 2: DNMT3A Expression profile from HPA (represented in: Euretos Knowledge Platform)
In addition, DNMT3A physically interacts with 97 gene involved in over 100 significantly associated physiological processes and pathways making the potential of possible side-effects even larger.
Figure 3: Associated pathways with DNMT3A (source: Euretos Knowledge Platform)
A better way forward may be to target one the 27 genes that regulate the expression of DNMT3A:
Figure 4: Genes that control the expression of DNMT3A (source: Euretos Knowledge Platform)
By selecting from these 27 regulators those with protein expression in monocytes, a list of 9 potential additional targets are identified, which each can be assessed in terms of druggability in comparison to DNMT3A.
Figure 5: Potential additional targets for DNMT3A based therapy (source: Euretos Knowledge Platform)
The DNMT3A gene is, in principle, an interesting potential novel target for neutralising the immune response evasion by tumors. It is however highly expressed and is involved in many other gene interactions. Regulators of DNMT3A expression that are also expressed in monocytes are alternative targets that would be worth considering als alternative therapeutic strategies
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About this series - The purpose of the Euretos Research Note series is to provide a data analytics perspective on recent life sciences publications. The series focuses on two types of questions: (1) Did the available data already point in the direction of a discovery? (2) What further research angles does the available data suggest?