Myc family proteins: Molecular drivers of tumorigenesis and resistance in neuroendocrine tumors

Neuroendocrine cancers are a diverse and poorly understood collection of malignancies derived from neuroendocrine cells throughout the body. These cancers uniquely exhibit properties of both the nervous and endocrine systems. Only a limited number of genetic driver mutations have been identified in neuroendocrine cancers, however the mechanisms of how these genetic aberrations alter tumor biology remain elusive. Recent studies have implicated the MYC family of transcription factors as important oncogenic factors in neuroendocrine tumors. We take a systematic approach to understand the roles of the MYC family (c-MYC, n-MYC, l-MYC) in the tumorigenesis of neuroendocrine cancers of the lung, GI tract, pancreas, kidney, prostate, pediatric neuroblastoma, and adrenal glands. Reflecting the complexity of neuroendocrine cancers, we highlight the roles of the MYC family in deregulating the cell cycle and transcriptional networks, invoking cellular plasticity, affecting proliferation capacity, aiding in chromatin remodeling, angiogenesis, metabolic changes, and resistance mechanisms. Depicting the diversity of neuroendocrine cancers, we suggest new approaches in understanding the underlying tumorigenic processes of neuroendocrine cancers from the perspective of MYC.