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Review
. 2023 Mar 9;24(6):5276.
doi: 10.3390/ijms24065276.

Kinase Inhibitors in Genetic Diseases

Lucia D'Antona  1   2 , Rosario Amato  1   2 , Carolina Brescia  1 , Valentina Rocca  2   3 , Emma Colao  2 , Rodolfo Iuliano  1   2 , Bonnie L Blazer-Yost  4 , Nicola Perrotti  1   2
Affiliations
Review

Kinase Inhibitors in Genetic Diseases

Lucia D'Antona et al. Int J Mol Sci. .

Abstract

Over the years, several studies have shown that kinase-regulated signaling pathways are involved in the development of rare genetic diseases. The study of the mechanisms underlying the onset of these diseases has opened a possible way for the development of targeted therapies using particular kinase inhibitors. Some of these are currently used to treat other diseases, such as cancer. This review aims to describe the possibilities of using kinase inhibitors in genetic pathologies such as tuberous sclerosis, RASopathies, and ciliopathies, describing the various pathways involved and the possible targets already identified or currently under study.

Keywords: RAS pathway; Wnt pathway; genetics; kinase inhibitors; mTOR pathway.

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Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1
Figure 1
The figure shows how the mTORC1 pathway is involved in the development of TSC. The figure shows the genes involved in the development of TSC and the pathway activated by different proteins. In particular, mTORC1 may contribute to the symptoms of TSC when hyperactivated by the malfunction of the TBC1D7 tuberin and hamartin complex. Two of the FDA-approved kinase inhibitors for the treatment of TSC are also shown in the figure.
Figure 2
Figure 2
The pathway of RAS/MAPK in RASopathies. The figure shows how the various genes of the Ras/MAPK pathway are involved in the development of the different syndromes associated with RASopathies. Shown are some of the MERK1/2 kinase inhibitors used to treat RASopathies, some of which are FDA-approved.
Figure 3
Figure 3
Canonical and non-canonical Wnt pathways. The canonical and noncanonical Wnt pathways are depicted in the figure with the various genes and mechanisms that are activated. In ciliopathies, several studies have shown that this pathway plays an essential role in their onset. Si113 is indicated; an SGK1 kinase inhibitor appears to have an effect on hydrocephalus caused by some ciliopathies.
Figure 4
Figure 4
Schematic representation of the composition of a cilium and the various mutated genes in ciliopathies. In the photo it is possible to observe how a cilium is structured in its various components. The different genes mutated in ciliopathies, and their location are represented.
See this image and copyright information in PMC

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