The success of targeted therapies in oncogene-driven cancer is limited by adaptive or acquired treatment resistance, leading to disease progression. A recent study reports that YAP-dependent human epidermal growth factor receptor 3 (HER3) activation constitutes a therapeutic vulnerability of adaptive resistance to RET-targeted therapies in RET-altered cancers, highlighting a promising strategy to improve RET inhibitor tumor responses. See related article by Katayama et al., p. 1127.