The researchers found that the upregulation of ERBB4 signaling triggered the activation of the RTK signaling pathway to sustain estrogen signaling in drug-resistant tumor cells during endocrine monotherapy; during the combination therapy, the surviving resistant tumor cells exhibited accelerated loss of estrogen signaling and increased activation of growth factor receptor and JNK-MAPK signaling pathways, which facilitated the proliferation of these tumor cells. The gene discussed is MAPK8; the disease is neoplasm.