Dual targeting of EGFR and ERBB2 pathways produces a synergistic effect on cancer cell proliferation and migration in vitro

Abstract

Members of the epidermal growth factor receptor (EGFR/ERBB) gene family are frequently dysregulated in a range of human cancers, and therapeutics targeting these proteins are in clinical use. We hypothesized that similar pathways are involved in feline and canine tumours and that the same drugs may be of clinical use in veterinary patients. We investigated EGFR and ERBB2 targeting using a panel of feline and canine cell lines. EGFR and ERBB2 were targeted with siRNAs or tyrosine kinase inhibitors (TKIs) and their effect on cellular proliferation, colony formation and migration was investigated in vitro. Here we report that EGFR and ERBB2 combined siRNA targeting produced synergistic effects in feline and canine cell lines similar to that reported in human cell lines. We conclude that dual EGFR and ERBB2 targeting using TKIs should be further evaluated as a potential new therapeutic strategy in feline head and neck and mammary tumours and canine mammary tumours.

New trends in glioma cancer therapy: Targeting Na+/H+ exchangers

“…Proliferation effects of NHE9 in GBM cells might mediate mitogen-activated protein kinase, which is a major effector in the EGFR network (Kondapalli et al, 2015). EGFR has an important role in the proliferation, migration, and mitosis of cancer cells (Gray et al, 2017;Tomas, Futter, & Eden, 2014). One study reported that microRNA-135a (miR-135a) downregulated the expression of NHE9 in glioblastoma cells.…”

Arctigenin induced gallbladder cancer senescence through modulating epidermal growth factor receptor pathway

“…11 Previous evidence indicated inhibition of EGFR signaling pathway induced cancer cell proliferation, migration, and cellular senescence. 12,13…”

“…11 Previous evidence indicated inhibition of EGFR signaling pathway induced cancer cell proliferation, migration, and cellular senescence. 12,13 Arctigenin (ATG), an active ingredient of Fructus arctii, has been reported to exhibit anti-inflammation and antitumor activity in various cancers. 14,15 ATG inhibits the growth of various cancer cells including colon cancer, ovarian cancer, hepatocellular carcinoma, gastric cancer, breast cancer, and bladder cancer, by inducing apoptosis [16][17][18][19] or cell cycle arrest [20][21][22][23] through iNOS/NO/STAT3/ Survivin (inducible nitric oxide synthase/nitric oxide/signal transducer and activator of transcription-3/Survivin) signaling, phosphatidylinositol-3-kinase (PI3K)/AKT signaling, reactive oxygen species (ROS)/p38 MAPK (mitogen-activated protein kinase) pathway, and phosphorylation of Retinoblastoma (Rb).…”

Molecular mechanisms of perineural spread of cutaneous carcinoma: a potential role for receptor tyrosine kinases and other biomarkers

“…(201) Lapatinib is a dual TKI that targets both EGFR and HER2 and has progressed to clinical trial in breast cancer. (202) Targeting the four members of the ERRB family in HNSCC with a mixture of six antibodies (pan-HER) has also recently been shown to reduce cell proliferation in vitro and achieve superior growth delay in a murine model compared to cetuximab or vehicle control.…”