Biology and evolution of poorly differentiated neuroendocrine tumors


Neuroendocrine (NE) cancers are a diverse group of neoplasms typically diagnosed and treated on the basis of their site of origin. This Perspective focuses on advances in our understanding of the tumorigenesis and treatment of poorly differentiated neuroendocrine tumors. Recent evidence from sequencing indicates that, although neuroendocrine tumors can arise de novo, they can also develop as a result of lineage plasticity in response to pressure from targeted therapies. We discuss the shared genomic alterations of these tumors independently of their site of origin, and we explore potential therapeutic strategies on the basis of recent biological findings.

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Figure 1: Frequency and incidence.
Figure 2: Cell of origin of neuroblastomas and current model of NEPC arising following anti-AR therapy as a mechanism of resistance.
Figure 3: Examples of tumors referred to as 'neuroendocrine.'


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Correspondence to Mark A Rubin.

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M.A.R., F.D., H.B. and D.S.R. have filed patent applications in the area of biomarkers and treatment for neuroendocrine prostate cancer. M.A.R., H.B. and D.S.R. have a sponsored research agreement in the area of neuroendocrine prostate cancer with Janssen Pharma.

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Rickman, D., Beltran, H., Demichelis, F. et al. Biology and evolution of poorly differentiated neuroendocrine tumors. Nat Med 23, 664–673 (2017).

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