Taken together, our findings support a model wherein ADT or AR inhibitor treatment stimulates ZBTB46 expression, which upregulates NGF-mediated CHRM4 stimulation; this plays a pivotal role in integrating AKT and MYCN signals to promote therapeutic resistance and neuroendocrine differentiation of prostate cancer (Fig. 7h). Here, CHRM4 is linked to Familial prostate cancer.