Diagnostic and molecular targeting INSM1-associated signaling axis in neuroendocrine tumors

Insulinoma-associated-1 (IA-1 or INSM1) cDNA encodes a zinc-finger transcription factor, which was isolated from a human insulinoma subtraction library, with specific expression patterns, predominantly in developing neuroendocrine (NE) tissues and tumors. INSM1 functions as a key differentiation factor in early pancreatic endocrine, sympatho-adrenal lineage, and pan-neurogenic precursor development. Deletion of INSM1 gene expression results in impairment of pancreatic beta-cells, catecholamine biosynthesis, and basal progenitor development during mammalian neocortex maturation. Recent studies revealed that elevated INSM1 expression in NE tumors (NETs) signifies that INSM1 is a superior biomarker for diagnostic and molecular target in NETs. NETs are tumors from cells that release hormones into the blood in response to a signaling from the nervous system. More than a dozen of NETs include carcinoid tumors, islet cell tumors, medullary thyroid cancer, pheochromocytomas, NE carcinoma of the skin (Merkel cell cancer), pulmonary NE tumors (small cell lung cancer, large cell NE carcinoma, and lung carcinoid), pituitary tumor, parathyroid carcinoma, gastroentero-pancreatic NE tumors, medulloblastoma, neuroblastoma, retinoblastoma, and genitourinary tract tumors (NE tumor of the cervix, prostate). Although they share similar NE features, it is known that distinct pathogenesis and oncogenic pathways are involved in each individual cancer. Therefore, it is feasible to target INSM1 biomarker and its associated signaling axis as a novel therapeutic approach for new options in NET treatment.