Class IA PI3K, the most important member of the PI3K complex, is composed of a heterodimer with a p85 regulatory subunit and a p110 catalytic subunit (PIK3CA), residing downstream of multiple receptor kinase families including ErbB RTK family (EGFR, HER2, HER3, HER4) and transducing signals originating from them [ 12, 13].
Sorafenib 1 is an FDA-approved drug for certain kidney and liver cancers that is known to inhibit multiple receptor tyrosine kinases and serine/threonine kinases.
This is consistent with the notion that the Src family Kinases cooperate with multiple receptor tyrosine Kinases to modulate signaling cross talk and promoting proliferation, adhesion, migration and invasion.
Dok family proteins are adaptor proteins that act as substrates of multiple receptor tyrosine kinases and non-receptor tyrosine kinases [ 5, 6].
BAK1 (BRI1-ASSOCIATED RECEPTOR KINASE) is a co-receptor of multiple receptor like kinases (RLK) and a regulator of cell death [ 35].
Sunitinib is an oral multi-targeted tyrosine kinase inhibitor that targets and blocks the signalling pathways of multiple receptor tyrosine kinases.
Those hyperphosphorylated in tumors include multiple receptor tyrosine kinases (listed in Table S2), and other signaling proteins, such as p38 delta, protein kinase C delta, and members of the PI3K signaling pathway, including p85 beta.
It has been reported that cancer cells typically express multiple receptor tyrosine kinases (RTKs) that mediate the upregulation of cell-survival effectors, generally, phosphatidylinositol-3-OH kinase (PI3K) and mitogen-activated protein kinase (MAPK) [ 4].
To date, sunitinib, an inhibitor of multiple receptor tyrosine kinases including KIT, PDGFRA, vascular endothelial growth factor receptor (VEGFR), and fms-related tyrosine kinase 3 (FLT3), is used as a second-line treatment providing clinical benefit in patients with imatinib-resistant GIST for a limited time period (Judson and Demetri, 2007).
We previously demonstrated co-activation of multiple receptor tyrosine kinases (RTKs), including epidermal growth factor receptor (EGFR), MET, and AXL in mesothelioma cell lines, suggesting that these kinases could serve as novel therapeutic targets.
