fig1

Figure 1. Signaling cross-talk within HER family receptors. HER family RTKs or growth factor receptors (EGFR (HER1/ErbB1), HER3 (ErbB3), HER4 (ErbB4), and IGF-IR) are able to activate several oncogenic signaling pathways such as Ras/Raf/MAPK/ERK or PI3K/Akt/mTOR to stimulate growth and proliferation. Direct inhibitors can inhibit HER2 including trastuzumab, pertuzumab, margetuzumab, or T-DM1 to block proliferation and cell growth. TDM-1, DS-8201, and SYD-985 are internalized through caveolae-mediated endocytosis to inhibit mitosis and facilitate DNA damage. Antibody conjugates that target HER3:HER2 complex include DS-8201, SYD-985, MCLA-128 which enhance cell mediated cytotoxicity in the cell. Direct antibody conjugates against EGFR neratinib, tucatinib, poziotinib, pyrotinib work to attenuate proliferation. Lapatinib, a HER2/EGFR inhibitor, attenuates cell proliferation, cell cycle regulation, and down-stream pathways. Images were created using Biorender.com. CDK 4/6: Cyclin-dependent kinase4/6; DM1: Derivative of Maytansine 1; EGFR: epidermal growth factor receptor; ER: estrogen receptor; HER2: Human epidermal growth factor receptor 2; HER3: Human epidermal growth factor receptor 3; IGF-1R: insulin-like growth factor 1 receptor; mTOR: mammalian Target of Rapamycin; PI3K: Phosphoinositide 3-kinase; Rb: Retinoblastoma protein. ERK: extracellular-signal regulated kinase