One of the first lines of defence
against infection is the innate immune system. This mounts a non-specific
response to infectious agents including bacteria and viruses. Recognition of bacterial
and viral components is accomplished by a family of receptors called Toll Like
Receptors (TLRs) found on the surface of innate immune cells. TLRs can also be
expressed by other cells such as cancer cells.
Previous studies have shown that
activation of TLRs can affect the levels of micro RNAs (miRNAs) in cells and
therefore regulate which proteins are expressed (I have mentioned the role of
miRNAs in cancer in previous posts). In this present study, Galli et al. found
that activation of TLR3 in prostate and breast cancer cells caused an increase
in four miRNAs. These miRNAs target a class of proteins called DNA methyltransferases,
resulting in the loss these proteins from the cancer cells. Without these DNA
methyltransferases a protein called retinoic acid receptor beta (RARβ) is produced by the cancer cells.
In a breakthrough, the group
showed that drugging tumours first with an activator of TLR3 followed by
retinoic acid (an activator of RARβ), caused tumours to be smaller compared to
control treated tumours. This study therefore presents promising pre-clinical
data for the treatment of breast and prostate cancer with this exciting
combination therapy.
Mentioned Articles
Galli R, Paone A,
Fabbri M, Zanesi N, Calore F, Cascione L, Acunzo M, Stoppacciaro A, Tubaro A,
Lovat F, Gasparini P, Fadda P, Alder H, Volinia S, Filippini A, Ziparo E,
Riccioli A, Croce CM.
Proc Natl Acad Sci U
S A. 2013 Jun 11;110(24):9812-7. doi: 10.1073/pnas.1304610110. Epub 2013 May
28.
Chen R, Alvero AB,
Silasi DA, Steffensen KD, Mor G.
Oncogene. 2008 Jan
7;27(2):225-33. doi: 10.1038/sj.onc.1210907.
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