Are miRNAs Suitable Targets for Cancer Therapy? - Therapeutic Strategies in Cancer Biology and Pathology - page 8

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Are miRNAs Suitable Targets for
Cancer Therapy?

The potential of miRNAs in targeted therapy against cancer was recognised with
the finding that loss of certain miRNAs is associated with some forms of leukae-
mia and solid tumours, but equally miRNAs have been found to be overexpressed
in other human neoplasia. Some miRNAs are differentially expressed in tumours
and tumour derived cell lines. Possibly, miRNAs might be either suppressors or
promoters of tumour development, which would be dependent upon the function of
the target genes or proteins. Of this there are numerous examples, where miRNAs
participate in the promotion or suppression of tumour by influencing the basic pro-
cesses involved in tumour development and progression. Not infrequently, members
of the same family can exert markedly different and diametrically opposite effects.
MiRNAs are known to be able to target several genes that regulate biological pro-
cesses highly relevant in the pathogenesis of human diseases. However, it has been
recognised that even a single miRNA might target a multitude of genes (Bartel,
2009). According to Lal et al. (2011) miRNA-34a alone can regulate hundreds of
genes. This equation makes the process of evaluating their relative significance a for-
midable task despite the advances in technology.

A Resumé of mTOR Signalling

The mTOR (mammalian target of rapamycin) signalling pathway has now pre-
eminently associated with several cellular processes such as cell proliferation,
growth, apoptosis, angiogenesis, cell motility and invasion. So its aberrant activation
provides cancer cells with a huge proliferative and invasive advantage and in this
way contribute significantly to the process of cancer metastasis. Recent identification
of phosphoinositide 3 kinase (PI3K)/Akt pathway with mTOR signalling has brought
growth factors into the arena of its activity. The mTOR pathway integrates oestro-
gen receptor (ER), epidermal growth factor receptor (EGFR), vascular endothelial
growth factor (VEGF) and insulin-like growth factor receptor (IGFR) signalling and
could facilitate cross talk between growth factor signalling pathways. The postulated
regulation of mTOR by the versatile miRNAs by direct means or via PTEN, modula-
tion of cytoskeletal dynamics, its perceived integration with the function of tumour-
and metastasis-suppressor genes has contributed much to emphasise its potential as a
therapeutic target. Inhibitors of mTOR signalling might offer potential new devices
for the management of triple negative breast cancer (TNBC). With the coverage here
concentrating on the modulation of biological response of cancer cells, especially