Human epidermal growth factor receptor 3 (HER3), a membrane-bound receptor tyrosine kinase disrupted in multiple cancers, including breast, lung and colorectal cancers, among others. HER3 controls a critical signal transduction and drug tolerance pathway, allowing cancer cells to escape from the effect of drugs against other HER family. The HER3 pathway is activated by binding the heregulin (HRG) with the HER3. High expression of HER3 in tumor tissues can be observed in patients who acquired resistance to HER family target therapies, such as cetuximab and trastuzumab. Therefore, HER3, as a key node in cellular signaling networks, is expected to be a prime target for cancer drug development.
AM-168 is a fully human anti-HER3 therapeutic antibody. In vitro and in vivo functional tests show that AM-168 can block the HER3 pathway by preventing the binding between HRG and the HER3. Additionally, administration of AM-168 demonstrated significant growth inhibition of xenograft tumors as monotherapy or in combination with other HER family inhibitors. AM-168 acting against HER3 has great potential as a novel agent for the treatment of solid tumors that bear resistance to EGFR or HER2.