Cancer models articles within Nature

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  • Article
    | Open Access

    Topobiologically complex mini-colons—which enable the faithful in vitro recapitulation of colorectal cancer tumorigenesis and its environmental determinants—offer the possibility to reduce animal use in a wide range of experimental applications.

    • L. Francisco Lorenzo-Martín
    • , Tania Hübscher
    •  & Matthias P. Lutolf

  • Article |

    A study reports the development of an algorithm, BISCUT, that detects genomic loci under selective pressure by relying on the distribution of breakpoints across chromosome arms, and uses it to explore how aneuploidies affect tumorigenesis.

    • Juliann Shih
    • , Shahab Sarmashghi
    •  & Rameen Beroukhim

  • Article
    | Open Access

    Skin tumour array by microporation (STAMP) captures the dynamic relationships of spatial, cellular and molecular components of tumour rejection and has the potential to translate therapeutic concepts into successful clinical strategies.

    • Guadalupe Ortiz-Muñoz
    • , Markus Brown
    •  & Christine Moussion

  • Article |

    A hierarchical model of melanoma tumour growth mirrors the cellular and molecular logic of cell-fate specification and differentiation of the underlying embryonic neural crest, and suggests that the ability to support growth and metastasis are limited to distinct pools of cells.

    • Panagiotis Karras
    • , Ignacio Bordeu
    •  & Jean-Christophe Marine

  • Article |

    In a zebrafish model of human cutaneous and acral melanomas, CRKL amplification causes tumours to favour a fin location, indicating that tumour location is determined by both the driver oncogenes and the pre-existing positional identity gene program.

    • Joshua M. Weiss
    • , Miranda V. Hunter
    •  & Richard M. White

  • Article
    | Open Access

    A method in which pooled barcoded human cancer cell lines are injected into a mouse xenograft model enables simultaneous mapping of the metastatic potential of multiple cell lines, and shows that breast cancer cells that metastasize to the brain have altered lipid metabolism.

    • Xin Jin
    • , Zelalem Demere
    •  & Todd R. Golub

  • Letter |

    A cell competition mechanism based on the differential expression of isoforms of Flower proteins is found in humans as well as Drosophila, and promotes tumorigenesis.

    • Esha Madan
    • , Christopher J. Pelham
    •  & Eduardo Moreno

  • Article |

    Analysis of growth dynamics in a dataset from 107 patients with chronic lymphocytic leukaemia (CLL) reveals both exponential and logistic patterns of growth, which are associated with differences in genetic attributes and clinical outcomes.

    • Michaela Gruber
    • , Ivana Bozic
    •  & Catherine J. Wu

  • Article |

    The original Cancer Cell Line Encyclopedia (CCLE) is expanded with deeper characterization of over 1,000 cell lines, including genomic, transcriptomic, and proteomic data, and integration with drug-sensitivity and gene-dependency data.

    • Mahmoud Ghandi
    • , Franklin W. Huang
    •  & William R. Sellers

  • Letter |

    Loss of RB promotes both malignant progression and the development of metastatic disease; however, whereas reactivation of the RB pathway can revert metastatic tumour cell states to non-metastatic cell states, malignant cell proliferation is supported by MAPK–CDK2-dependent suppression of RB.

    • David M. Walter
    • , Travis J. Yates
    •  & David M. Feldser

  • Letter |

    Mutations in the nucleotidase-encoding gene NT5C2 drive chemotherapy resistance in relapsed acute lymphoid leukaemia but the mutations also lead to a loss-of-fitness phenotype and to collateral drug sensitivity, which could be exploited for therapy.

    • Gannie Tzoneva
    • , Chelsea L. Dieck
    •  & Adolfo A. Ferrando

  • Letter |

    A protocol producing orthotopic patient-derived xenografts at diagnosis, recurrence, and autopsy demonstrates proof of principle for using these tumours for basic and translational research on paediatric solid tumours.

    • Elizabeth Stewart
    • , Sara M. Federico
    •  & Michael A. Dyer

  • Letter |

    Kinase-inactive Braf mutants can initiate the development of lung adenocarcinoma in mice; co-expression of activated Kras enhances tumour initiation and progression, and wild-type Braf is required to sustain tumorigenesis.

    • Patricia Nieto
    • , Chiara Ambrogio
    •  & David Santamaría

  • Letter |

    Genetically engineered ‘lymphoreporter’ mouse strains are used to track melanoma dissemination in vivo, identifying midkine as a tumour-secreted factor that acts at a distance, preparing pre-metastatic niches and serving as an indicator of poor prognosis in patients.

    • David Olmeda
    • , Daniela Cerezo-Wallis
    •  & María S. Soengas

  • Letter |

    During early-stage tumour growth in Drosphila, tumour cells acquire necessary nutrients by triggering autophagy in surrounding cells in the tumour microenvironment.

    • Nadja S. Katheder
    • , Rojyar Khezri
    •  & Tor Erik Rusten

  • Analysis |

    Large-scale analyses of the drug sensitivity of cancer cell lines have been previously reported to yield conflicting conclusions; this Analysis uses independently generated data to demonstrate that consistency can be achieved if key laboratory and data analysis practices are considered when future studies are undertaken.

    • Peter M. Haverty
    • , Eva Lin
    •  & Richard Bourgon

  • Analysis |

    In panels of cancer cell lines analysed for their response to drug libraries, some studies have proposed distinct pharmacological sensitivities for some cell lines while other studies have not seen the same trends; here the data in the Cancer Cell Line Encyclopedia and the Genomics of Drug Sensitivity in Cancer are reassessed, and the authors report a stronger degree of concordance between the two data sets than that in a previous study.

    • Nicolas Stransky
    • , Mahmoud Ghandi
    •  & Julio Saez-Rodriguez

  • Letter |

    This study finds that the Hippo pathway is essential for gut epithelial regeneration and tumour initiation; the Hippo component Yap holds off differentiation of intestinal stem cells to Paneth cells to promote a survival and self-renewal regenerative program through activation of the Egfr pathway.

    • Alex Gregorieff
    • , Yu Liu
    •  & Jeffrey L. Wrana

  • Letter |

    Parasites of the Theileria genus infect cattle and transform their host cells, a transformation that can be reversed by treatment with the drug buparvaquone; here, a Theileria homologue of the peptidyl-prolyl isomerase PIN1 is shown to be secreted into the host cell, where it promotes transformation and can be directly inhibited by buparvaquone.

    • J. Marsolier
    • , M. Perichon
    •  & J. B. Weitzman

  • Letter |

    The mTORC1 complex has been implicated in tumorigenesis owing partially to its ability to increase protein translation; now, mTORC1 activity in the mouse intestine is shown not to be required for normal homeostasis but to be necessary for the triggering of tumorigenesis by APC mutations, suggesting that it could be a good target for the prevention of colorectal cancer in high-risk patients.

    • William J. Faller
    • , Thomas J. Jackson
    •  & Owen J. Sansom

  • Letter |

    Whole-exome sequencing is used to compare the mutational landscape of adenomas from three mouse models of non-small-cell lung cancer, induced either by exposure to carcinogens or by genetic mutation of Kras; the results reveal that the two types of tumour have different mutational profiles and adopt different routes to tumour development.

    • Peter M. K. Westcott
    • , Kyle D. Halliwill
    •  & Allan Balmain

  • Letter |

    The CRISPR/Cas system has been used in mice for genome editing to introduce genetic alterations found in human lung tumours, and these genome modifications resulted in mouse lung tumours showing different histopathologies depending on the genes altered; the CRISPR/Cas system offers improved and faster ways to create animal models of human diseases such as cancer.

    • Francisco J. Sánchez-Rivera
    • , Thales Papagiannakopoulos
    •  & Tyler Jacks

  • Letter |

    CRISPR plasmids targeting Pten and p53, alone and in combination, are delivered by hydrodynamic injection to the liver; the CRISPR-mediated mutations phenocopy the effects of deletions using Cre–LoxP technology, allowing the direct mutation of tumour suppressor genes and oncogenes in the liver using the CRISPR/Cas system, which presents a new approach for rapid development of liver cancer models and functional genomics.

    • Wen Xue
    • , Sidi Chen
    •  & Tyler Jacks

  • Letter |

    Gain-of-function mutations in isocitrate dehydrogenase (IDH) are among the most common genetic alterations in intrahepatic cholangiocarcinoma (IHCC), a deadly cancer of the liver bile ducts; now mutant IDH is shown to block liver cell differentiation through the suppression of HNF-4α, a master regulator of hepatocyte identity and quiescence, leading to expansion of liver progenitor cells primed for progression to IHCC.

    • Supriya K. Saha
    • , Christine A. Parachoniak
    •  & Nabeel Bardeesy

  • Letter |

    A new mechanism by which acute myeloid leukaemia patients become resistant to Ara-C and a newer treatment, ribavirin, is uncovered; these drugs can be glucuronidated and thereby inactivated by members of the UDP glucuronosyltransferase family of enzymes activated through GLI1 signalling.

    • Hiba Ahmad Zahreddine
    • , Biljana Culjkovic-Kraljacic
    •  & Katherine L. B. Borden

  • Letter |

    A mouse model of T-cell leukaemia is used to test whether PTEN loss is required for tumour maintenance as well as initiation; although it had little effect on tumour load in haematopoietic organs, PTEN reactivation reduced the CCR9-dependent tumour dissemination to the intestine that was amplified on PTEN loss, exposing the importance of tumour microenvironment in PTEN-deficient settings.

    • Cornelius Miething
    • , Claudio Scuoppo
    •  & Scott W. Lowe

  • Outlook |

    Leukaemia treatments must eliminate the versatile cells that can bring the cancer back to life years later.

    • Cassandra Willyard

  • Outlook |

    Technologies that rapidly sequence DNA reveal deep genetic diversity both within and among individuals with leukaemia.

    • Sarah DeWeerdt

  • Letter |

    Obesity is shown in a mouse model of liver cancer to strongly enhance tumorigenesis; a high fat diet alters the composition of intestinal bacteria, leading to more production of the metabolite DCA which, probably together with other factors, induces senescence and the secretion of various senescence-associated cytokines in hepatic stellate cells, thus promoting cancer.

    • Shin Yoshimoto
    • , Tze Mun Loo
    •  & Naoko Ohtani

  • Letter |

    Naked mole rats seem almost entirely protected from developing cancer, and this can now, at least in part, be explained by the production of a unique high-molecular-mass form of hyaluronan, a component of the extracellular matrix; together with an increased sensitivity of naked mole-rat cells to hyaluronan signalling, this form protects its cells from oncogenic transformation.

    • Xiao Tian
    • , Jorge Azpurua
    •  & Andrei Seluanov

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