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    Expanding therapeutic opportunities for Extra-Pulmonary Neuroendocrine Carcinoma

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    Authors
    Frizziero, Melissa
    Kilgour, Elaine
    Simpson, Kathryn
    Rothwell, Dominic G
    Moore, D. A.
    Frese, Kristopher K
    Galvin, M.
    Lamarca, Angela
    Hubner, Richard A
    Valle, Juan W
    McNamara, Mairéad G
    Dive, Caroline
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    Affiliation
    Cancer Biomarker Centre, Cancer Research UK Manchester Institute. Clinical and Experimental Pharmacology Group, Cancer Research UK Manchester Institute. Department of Oncology, UCL Cancer Centre. Christie Hospital NHS Foundation Trust. Medical Oncology, The Christie Hospital. Medical Oncology, University of Manchester. Cancer Biomarker Centre, Cancer Research UK Manchester Institute caroline.dive@cruk.manchester.ac.uk.
    Issue Date
    2022
    
    Metadata
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    Abstract
    Poorly-Differentiated NeuroEndocrine Carcinomas (PD-NECs) are rare cancers garnering interest as they become more commonly encountered in clinic. This is due to improved diagnostic methods and the increasingly observed phenomenon of 'NE lineage plasticity', whereby non-NeuroEndocrine (non-NE) epithelial cancers transition to aggressive NE phenotypes after targeted treatment. Effective treatment options for patients with PD-NEC is challenging for several reasons. This includes a lack of targetable, recurrent molecular drivers, a paucity of patient-relevant preclinical models to study biology and test novel therapeutics, and the absence of validated biomarkers to guide clinical management. Whilst advances have been made pertaining to molecular subtyping of Small Cell Lung Cancer (SCLC), a PD-NEC of lung origin, Extra-Pulmonary (EP)-PD-NECs remain understudied. This review will address emerging SCLC-like, same-organ non-NE cancer-like and tumour type-agnostic biological vulnerabilities of EP-PD-NECs, with the potential for therapeutic exploitation. The hypotheses surrounding the origin of these cancers and how 'NE lineage plasticity' can be leveraged for therapeutic purposes is discussed. SCLC is herein proposed as a paradigm for supporting progress towards precision medicine in EP-PD-NECs. The aim of this review is to provide a thorough portrait of the current knowledge of EP-PD-NEC biology, with a view to informing new avenues for research and future therapeutic opportunities in these cancers of unmet need.
    Citation
    Frizziero M, Kilgour E, Simpson KL, Rothwell DG, Moore DA, Frese KK, et al. Expanding therapeutic opportunities for Extra-Pulmonary Neuroendocrine Carcinoma. Clinical Cancer Research. American Association for Cancer Research (AACR); 2022. p. clincanres.3058.2021.
    Journal
    Clinical Cancer Research
    URI
    http://hdl.handle.net/10541/625063
    DOI
    10.1158/1078-0432.Ccr-21-3058
    PubMed ID
    35091446
    Additional Links
    https://dx.doi.org/10.1158/1078-0432.Ccr-21-3058
    Type
    Article
    Language
    en
    ae974a485f413a2113503eed53cd6c53
    10.1158/1078-0432.Ccr-21-3058
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