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Small-Molecule Targeted Therapies
Published in David E. Thurston, Ilona Pysz, Chemistry and Pharmacology of Anticancer Drugs, 2021
At the molecular level, nilotinib has been shown to inhibit kinases including Bcr-Abl, Kit, Lck, EPHA3, EPHA8, DDR1, DDR2, PDGFRB, MAPK11, and ZAK. However, it does not inhibit the Src kinase, a key regulator of other tyrosine kinase proteins that influence whether cells proliferate or die. The binding of nilotinib to its target Bcr-Abl protein is energetically more favorable than that of imatinib, and it has been shown to have an approximately 20-fold increase in potency compared to imatinib in in vitro kinase inhibition and cellular proliferation assays.
CBL Syndrome
Published in Dongyou Liu, Handbook of Tumor Syndromes, 2020
Mapped to chromosome 11q23.3, which is the long (q) arm of chromosome 11 at position 23.3, the Casitas B-lineage lymphoma (CBL) gene spans >110 kb with 16 exons and encodes a RING finger E3 ubiquitin ligase. As an adaptor protein with ubiquitin ligase activity, CBL mediates the conjugation of ubiquitin to activated receptor tyrosine kinases (RTK), such as KIT, FLT1, FGFR1, FGFR2, PDGFRA, PDGFRB, EGFR, CSF1R, EPHA8, and KDR. This conjugation is required for receptor internalization, endocytic sorting, and switching off signaling via receptor degradation or recycling. Besides involvement in signal transduction in hematopoietic cells, CBL plays an important role in the regulation of osteoblast differentiation and apoptosis [13,14].
The role of Eph receptors in cancer and how to target them: novel approaches in cancer treatment
Published in Expert Opinion on Investigational Drugs, 2020
Oscar J Buckens, Btissame El Hassouni, Elisa Giovannetti, Godefridus J Peters
In epithelial ovarian cancer, overexpression of EphA8 was associated with a higher level of metastasis and this receptor may be useful as a prognostic marker [81]. Similarly, in oral tongue squamous cell carcinoma, EphA8 promotes progression of the tumor. Liu et al. [81] showed that these effects might be due to the effect on invasion of the tumor but not on proliferation. However, more information about the mechanism underlying EphA8 function is warranted.