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  • HER2 signaling via the HER2/HER3 heterodimer drives tumor cell proliferation and survival1,2
  • The HER2/HER3 heterodimer delivers the most potent signal for proliferation in tumor cells that overexpress HER22-4
  • Targeting other HER family members, such as EGFR (HER1), does not functionally suppress HER2 signaling, and may introduce off-target toxicities such as diarrhea and rash5-9

HER2 inhibition is being explored as a treatment approach in multiple tumor types, including mCRC.10

Optimizing treatment through simultaneous HER2 inhibition

EGFR = epidermal growth factor receptor; HER = human epidermal growth factor receptor.

References: 1. Hsieh AC, Moasser MM. Targeting HER proteins in cancer therapy and the role of the non-target HER3. Br J Cancer. 2007;97(4):453-457. 2. Tai W, Mahato R, Cheng K. The role of HER2 in cancer therapy and targeted drug delivery. J Control Release. 2010;146(3):264-275. 3. Siena S, Sartore-Bianchi A, Marsoni S, et al. Targeting the human epidermal growth factor receptor 2 (HER2) oncogene in colorectal cancer. Ann Oncol. 2018;29(5):1108-1119. 4. Pinkas-Kramarski R, Soussan L, Waterman H, et al. Diversification of Neu differentiation factor and epidermal growth factor signaling by combinatorial receptor interactions. EMBO J. 1996;15(10):2452-2467. 5. Lee-Hoeflich ST, Crocker L, Yao E, et al. A central role for HER3 in HER2-amplified breast cancer: implications for targeted therapy. Cancer Res. 2008;68(14):5878-5887. 6. Harandi A, Zaidi AS, Stocker AM, Laber DA. Clinical efficacy and toxicity of anti-EGFR therapy in common cancers. J Oncol. 2009;2009:567486. 7. Arteaga CL, O'Neill A, Moulder SL, et al. A phase I-II study of combined blockade of the ErbB receptor network with trastuzumab and gefitinib in patients with HER2 (ErbB2)-overexpressing metastatic breast cancer. Clin Cancer Res. 2008;14(19):6277-6283. 8. Jackson-Fisher AJ, Bellinger G, Shum E, et al. Formation of Neu/ErbB2-induced mammary tumors is unaffected by loss of ErbB4. Oncogene. 2006;25(41):5664-5672. 9. Li J. Diarrhea with HER2-targeted agents in cancer patients: a systematic review and meta-analysis. J Clin Pharmacol. 2019;59(7):935-946. 10. Oh D-Y, Bang Y-J. HER2-targeted therapies — a role beyond breast cancer. Nat Rev Clin Oncol. 2020;17(1):33-48