In agreement with Shen et al.’s propositions on ‘genes with both oncogenic and tumor suppressor functions’ [28], it is probable that non-silent, function-altering mutations, such as frameshift or point mutations in TACSTD2, are the principal drivers of the prevalent tumor-limiting and therapy-sensitizing TACSTD2 signaling in CRPC, documented herein. This evidence concerns the gene TACSTD2 and neoplasm.