(Arg)9-SH2 superbinder: a novel promising anticancer therapy to melanoma by blocking phosphotyrosine signaling

Abstract

[...]it is necessary and urgent to address the problems of drug resistance to inhibitors with BRAF-mutant and lacking appropriate therapies for patients without specific mutations. SH2 superbinder, strongly binding with diverse pY sites to block related signal transduction pathways, can recognize other sites instead, even if mutation alters the pY site [14, 15]. [...]SH2 superbinder can achieve the purpose of killing cancer cells [16]. Due to its strong binding ability with pY-containing proteins, (Arg)9-GST SH2 TrM may decrease the tyrosine phosphorylation level of proteins derived from EGFR and act as an inhibitor of EGFR signaling and EGF-dependent cell growth. [...]Grb2, a critical adaptor protein in EGFR signaling [26], was found to bind less to EGFR after cells treated with (Arg)9-GST SH2 TrM (Fig. 4b). (Arg)9-GST SH2 TrM suppressed the growth of B16F10 cells on tumor-bearing mice To further confirm the role of (Arg)9-GST SH2 TrM in vivo, mice were injected subcutaneously with 1 × 106 B16F10 cells on the right flanks. Since the 9th day, mice were injected with (Arg)9-GST SH2 TrM or PBS through tail vein twice a day (10 mg/kg).