Targeting RTK Signaling Pathways in Cancer

Abstract

The RAS/MAP kinase and the RAS/PI3K/AKT pathways play a key role in the regulation of proliferation, differentiation and survival. The induction of these pathways depends on Receptor Tyrosine Kinases (RTKs) that are activated upon ligand binding. In cancer, constitutive and aberrant activations of components of those pathways result in increased proliferation, survival and metastasis. For instance, mutations affecting RTKs, Ras, B-Raf, PI3K and AKT are common in perpetuating the malignancy of several types of cancers and from different tissue origins. Therefore, these signaling pathways became prime targets for cancer therapy. This review aims to provide an overview about the most frequently encountered mutations, the pathogenesis that results from such mutations and the known therapeutic strategies developed to counteract their aberrant functions.

Comprehensive review on cardio-oncology: Role of multimodality imaging

“…Small-molecule tyrosine kinase inhibitors (TKI) targeting both EGFR and HER2 receptors include lapatinib (Tykerb) and afatinib; sunitinib and soratinib block both PDGFR and VEGFR to inhibit angiogenesis. 32 HF and LV dysfunction have been reported with several small-molecule tyrosine kinase inhibitors, including dasatinib, lapatinib, imatinib, and sunitinib. 31 Sunitinib-associated LV systolic dysfunction and HF appear to be reversible and generally respond to medical therapy.…”

“…These receptors include several sub-families, such as epidermal growth factor receptors (EGFRs), vascular endothelial growth factor receptors (VEGFRs), fibroblast growth factor receptors (FGFRs), insulin and insulin-like growth factor receptors (IR and IGFR), platelet-derived growth factor receptors (PDGFRs), proto-oncogene c-KIT, and hepatocyte growth factor receptors (HGFRs), which are targeted by tyrosine kinase inhibitors in the treatment of cancer. 32 VEGF receptors play a crucial role in vasculogenesis and angiogenesis. VEGFR inhibitors, blocking angiogenesis and lymphangiogenesis, are clinically useful for minimizing the risk of tumor growth and metastasis.…”

Green Tea Catechins for Prostate Cancer Prevention: Present Achievements and Future Challenges

“…The binding of a growth factor or a cytokine to the extracellular domain of RTKs induces the dimerization and autophosphorylation of the RTKs on specific tyrosine residues and activation of downstream intracellular signaling that include Ras/ERK/MAPK and PI3K/Akt. Ras/ERK/MAPK and PI3K/Akt activation triggers a cascade of molecular events involving enzymes, proteins and transcription factors that have been extensively reviewed in [66]. The activation of cell surface RTKs controls many key important processes in normal cells such as cell proliferation, differentiation, survival and migration.…”

“…The activation of cell surface RTKs controls many key important processes in normal cells such as cell proliferation, differentiation, survival and migration. These receptor-associated pathways have been found altered in tumors cells, including PCa [55,[66][67][68][69]. The RTKs family comprises epidermal growth factor receptors (EGFRs), fibroblast growth factor receptors (FGFRs), insulin-like growth factor receptors (IGF-R), platelet-derived growth factor receptors (PDGFRs), vascular endothelial growth factor receptors (VEGFRs), hepatocyte growth factor receptors (HGFRs) also known as Met.…”

Identification of Subsets of Genetic Alterations in KRAS-mutant Lung Cancer using Association Rule Mining

“…Rearrangement of ALK and ROS1 genes are targeted with crizotinib and ceritinib [7]. Progress has also been made in targeting mutations in the other RTKs [3,8]. However, for tumors containing alterations in KRAS, there are no FDA approved drugs.…”