The Human Epidermal Growth Factor Receptor 3 (HER3) signals through forming heterodimers with EGFR or HER2 in order to activate the PI3K pathway. To date, targeting HER3 with antibodies has shown sub-optimal results. To combat this, Thakkar and colleagues designed a picomolar antibody (10DF1) that targets HER3 at the heterodimerization interface. 10DF1 potently inhibited heterodimerization with EGFR and HER2 and restricted PI3K signaling. 10D1F showed in vivo tumor growth inhibition in mouse models of gastric, lung, head and neck, and ovarian cancers. 10DF1 therefore represents a novel class of anti-HER3 neutralizing antibodies with clinical promise in multiple cancer indications.

Despite advances in BRAF and MEK inhibitors, many patients develop resistance within one year. In the majority of cases, this resistance is due to ERK reactivation. In this manuscript, Bhagwat and colleagues outline the preclinical activity of LY3214996, a potent, selective, ATP competitive ERK inhibitor designed to overcome this resistance. LY3214996...

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