• Login
    View Item 
    •   Home
    • The Manchester Institute Cancer Research UK
    • All Paterson Institute for Cancer Research
    • View Item
    •   Home
    • The Manchester Institute Cancer Research UK
    • All Paterson Institute for Cancer Research
    • View Item
    JavaScript is disabled for your browser. Some features of this site may not work without it.

    Browse

    All of ChristieCommunitiesTitleAuthorsIssue DateSubmit DateSubjectsThis CollectionTitleAuthorsIssue DateSubmit DateSubjectsProfilesView

    My Account

    LoginRegister

    Local Links

    The Christie WebsiteChristie Library and Knowledge Service

    Statistics

    Display statistics

    Signaling pathway screening platforms are an efficient approach to identify therapeutic targets in cancers that lack known driver mutations: a case report for a cancer of unknown primary origin.

    • CSV
    • RefMan
    • EndNote
    • BibTex
    • RefWorks
    Thumbnail
    Name:
    s41525-018-0055-6.pdf
    Size:
    1.578Mb
    Format:
    PDF
    Description:
    Full text, Open Access article
    Download
    Authors
    Torres-Ayuso, Pedro
    Sahoo, Sudhakar
    Ashton, Garry
    An, Elvira
    Simms, Nicole
    Galvin, Melanie
    Leong, Hui Sun
    Frese, Kristopher K
    Simpson, Kathryn L
    Cook, Natalie
    Hughes, Andrew
    Miller, Crispin J
    Marais, Richard
    Dive, Caroline
    Krebs, Matthew G
    Brognard, John
    Show allShow less
    Affiliation
    Signalling Networks in Cancer Group, Cancer Research UK, Manchester Institute, University of Manchester, Manchester, M20 4BX UK
    Issue Date
    2018
    
    Metadata
    Show full item record
    Abstract
    Precision medicine aims to tailor cancer therapies to target specific tumor-promoting aberrations. For tumors that lack actionable drivers, which occurs frequently in the clinic, extensive molecular characterization and pre-clinical drug efficacy studies will be required. A cell line maintained at low passage and a patient- derived xenograft model (PDX) were generated using a fresh biopsy from a patient with a poorly-differentiated neuroendocrine tumor of unknown primary origin. Next-generation sequencing, high throughput signaling network analysis, and drug efficacy trials were then conducted to identify actionable targets for therapeutic intervention. No actionable mutations were identified after whole exome sequencing of the patient's DNA. However, whole genome sequencing revealed amplification of the 3q and 5p chromosomal arms, that include the PIK3CA and RICTOR genes, respectively. We then conducted pathway analysis, which revealed activation of the AKT pathway. Based on this analysis, efficacy of PIK3CA and AKT inhibitors were evaluated in the tumor biopsy-derived cell culture and PDX, and response to the AKT inhibitor AZD5363 was observed both in vitro and in vivo indicating the patient would benefit from targeted therapies directed against the serine/threonine kinase AKT. In conclusion, our study demonstrates that high throughput signaling pathway analysis will significantly aid in identifying actionable alterations in rare tumors and guide patient stratification into early-phase clinical trials.
    Citation
    Signaling pathway screening platforms are an efficient approach to identify therapeutic targets in cancers that lack known driver mutations: a case report for a cancer of unknown primary origin. 2018, 3: 15 NPJ Genom Med
    Journal
    NPJ genomic medicine
    URI
    http://hdl.handle.net/10541/621160
    DOI
    10.1038/s41525-018-0055-6
    PubMed ID
    29951225
    Type
    Article
    Language
    en
    ISSN
    2056-7944
    ae974a485f413a2113503eed53cd6c53
    10.1038/s41525-018-0055-6
    Scopus Count
    Collections
    All Paterson Institute for Cancer Research

    entitlement

    Related articles

    • Guidance to rational use of pharmaceuticals in gallbladder sarcomatoid carcinoma using patient-derived cancer cells and whole exome sequencing.
    • Authors: Feng F, Cheng Q, Yang L, Zhang D, Ji S, Zhang Q, Lin Y, Li F, Xiong L, Liu C, Jiang X
    • Issue date: 2017 Jan 17
    • [Lung cancer molecular testing, what role for Next Generation Sequencing and circulating tumor DNA].
    • Authors: Pécuchet N, Legras A, Laurent-Puig P, Blons H
    • Issue date: 2016 Jan
    • Combination of PI3K and MEK inhibitors yields durable remission in PDX models of PIK3CA-mutated metaplastic breast cancers.
    • Authors: Coussy F, El Botty R, Lavigne M, Gu C, Fuhrmann L, Briaux A, de Koning L, Dahmani A, Montaudon E, Morisset L, Huguet L, Sourd L, Painsec P, Chateau-Joubert S, Larcher T, Vacher S, Melaabi S, Salomon AV, Marangoni E, Bieche I
    • Issue date: 2020 Feb 22
    • Integration of genomics, high throughput drug screening, and personalized xenograft models as a novel precision medicine paradigm for high risk pediatric cancer.
    • Authors: Tsoli M, Wadham C, Pinese M, Failes T, Joshi S, Mould E, Yin JX, Gayevskiy V, Kumar A, Kaplan W, Ekert PG, Saletta F, Franshaw L, Liu J, Gifford A, Weber MA, Rodriguez M, Cohn RJ, Arndt G, Tyrrell V, Haber M, Trahair T, Marshall GM, McDonald K, Cowley MJ, Ziegler DS
    • Issue date: 2018
    • Clinical Actionability of Molecular Targets in Multi-Ethnic Breast Cancer Patients: A Retrospective Single-Institutional Study.
    • Authors: Kang I, Naghi L, Yost SE, Mortimer J
    • Issue date: 2025 May
    DSpace software (copyright © 2002 - 2025)  DuraSpace
    Quick Guide | Contact Us
    Open Repository is a service operated by 
    Atmire NV
     

    Export search results

    The export option will allow you to export the current search results of the entered query to a file. Different formats are available for download. To export the items, click on the button corresponding with the preferred download format.

    By default, clicking on the export buttons will result in a download of the allowed maximum amount of items.

    To select a subset of the search results, click "Selective Export" button and make a selection of the items you want to export. The amount of items that can be exported at once is similarly restricted as the full export.

    After making a selection, click one of the export format buttons. The amount of items that will be exported is indicated in the bubble next to export format.