AI Article Synopsis
- Receptor tyrosine kinases (RTKs) play a crucial role in cell signaling related to growth, survival, and migration, but cancer can lead to their overactivation.
- Cancerous cells can create fusion proteins via RTK translocations, activating these kinases constantly and changing their normal functions.
- While RTK translocations are uncommon in blood cancers, targeted inhibitors show promise in treating patients with these specific genetic changes.
Article Abstract
Receptor tyrosine kinases (RTKs) activate various signaling pathways and regulate cellular proliferation, survival, migration, and angiogenesis. Malignant neoplasms often circumvent or subjugate these pathways by promoting RTK overactivation through mutation or chromosomal translocation. RTK translocations create a fusion protein containing a dimerizing partner fused to an RTK kinase domain, resulting in constitutive kinase domain activation, altered RTK cellular localization, upregulation of downstream signaling, and novel pathway activation. While RTK translocations in hematological malignancies are relatively rare, clinical evidence suggests that patients with these genetic abnormalities benefit from RTK-targeted inhibitors. Here, we present a timely review of an exciting field by examining RTK chromosomal translocations in hematological cancers, such as Anaplastic Lymphoma Kinase (ALK), Fibroblast Growth Factor Receptor (FGFR), Platelet-Derived Growth Factor Receptor (PDGFR), REarranged during Transfection (RET), Colony Stimulating Factor 1 Receptor (CSF1R), and Neurotrophic Tyrosine Kinase Receptor Type 3 (NTRK3) fusions, and discuss current therapeutic options.
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| http://dx.doi.org/10.1016/j.molmed.2016.11.002 | DOI Listing |
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