Latest Research

  • Article |

    Stewart et al. use circulating tumor cell-derived xenografts from patients with small-cell lung cancer to study tumor heterogeneity following the onset of therapeutic resistance.

    • C. Allison Stewart
    • , Carl M. Gay
    • , Yuanxin Xi
    • , Santhosh Sivajothi
    • , V. Sivakamasundari
    • , Junya Fujimoto
    • , Mohan Bolisetty
    • , Patrice M. Hartsfield
    • , Veerakumar Balasubramaniyan
    • , Milind D. Chalishazar
    • , Cesar Moran
    • , Neda Kalhor
    • , John Stewart
    • , Hai Tran
    • , Stephen G. Swisher
    • , Jack A. Roth
    • , Jianjun Zhang
    • , John de Groot
    • , Bonnie Glisson
    • , Trudy G. Oliver
    • , John V. Heymach
    • , Ignacio Wistuba
    • , Paul Robson
    • , Jing Wang
    •  & Lauren Averett Byers
  • Analysis |

    Degasperi et al. introduce a practical framework and Signal, an online tool, to analyze mutational signatures. They find evidence of tissue-specific variability in mutational signatures, which may impact tumor classification and clinical application.

    • Andrea Degasperi
    • , Tauanne Dias Amarante
    • , Jan Czarnecki
    • , Scott Shooter
    • , Xueqing Zou
    • , Dominik Glodzik
    • , Sandro Morganella
    • , Arjun S. Nanda
    • , Cherif Badja
    • , Gene Koh
    • , Sophie E. Momen
    • , Ilias Georgakopoulos-Soares
    • , João M. L. Dias
    • , Jamie Young
    • , Yasin Memari
    • , Helen Davies
    •  & Serena Nik-Zainal
  • Article |

    Bodenmiller and colleagues pair imaging mass cytometry with data from the METABRIC cohort to define single-cell phenotypic and genomic features of breast cancer with spatial context, finding associations with breast cancer subtypes and prognosis.

    • H. Raza Ali
    • , Hartland W. Jackson
    • , Vito R. T. Zanotelli
    • , Esther Danenberg
    • , Jana R. Fischer
    • , Helen Bardwell
    • , Elena Provenzano
    • , H. Raza Ali
    • , M. Al Sa’d
    • , S. Alon
    • , Samuel Aparicio
    • , G. Battistoni
    • , S. Balasubramanian
    • , R. Becker
    • , Bernd Bodenmiller
    • , E. S. Boyden
    • , D. Bressan
    • , A. Bruna
    • , B. Marcel
    • , Carlos Caldas
    • , M. Callari
    • , I. G. Cannell
    • , H. Casbolt
    • , N. Chornay
    • , Y. Cui
    • , A. Dariush
    • , K. Dinh
    • , A. Emenari
    • , Y. Eyal-Lubling
    • , J. Fan
    • , E. Fisher
    • , E. A. González-Solares
    • , C. González-Fernández
    • , D. Goodwin
    • , W. Greenwood
    • , F. Grimaldi
    • , G. J. Hannon
    • , O. Harris
    • , S. Harris
    • , C. Jauset
    • , J. A. Joyce
    • , E. D. Karagiannis
    • , T. Kovačević
    • , L. Kuett
    • , R. Kunes
    • , A. Küpcü Yoldaş
    • , D. Lai
    • , E. Laks
    • , H. Lee
    • , M. Lee
    • , G. Lerda
    • , Y. Li
    • , A. McPherson
    • , N. Millar
    • , C. M. Mulvey
    • , F. Nugent
    • , C. H. O’Flanagan
    • , M. Paez-Ribes
    • , I. Pearsall
    • , F. Qosaj
    • , A. J. Roth
    • , Oscar M. Rueda
    • , T. Ruiz
    • , K. Sawicka
    • , L. A. Sepúlveda
    • , S. P. Shah
    • , A. Shea
    • , A. Sinha
    • , A. Smith
    • , S. Tavaré
    • , S. Tietscher
    • , I. Vázquez-García
    • , S. L. Vogl
    • , N. A. Walton
    • , A. T. Wassie
    • , S. S. Watson
    • , S. A. Wild
    • , E. Williams
    • , J. Windhager
    • , C. Xia
    • , P. Zheng
    • , X. Zhuang
    • , Oscar M. Rueda
    • , Suet-Feung Chin
    • , Samuel Aparicio
    • , Carlos Caldas
    •  & Bernd Bodenmiller
  • Article |

    Marais and colleagues report that checkpoint inhibitor treatment of patients with melanoma leads to dynamic changes in peripheral T cells and expansion of immune effector cells. This awakening of the immune system occurs early after treatment and could be exploited in the clinic.

    • Sara Valpione
    • , Elena Galvani
    • , Joshua Tweedy
    • , Piyushkumar A. Mundra
    • , Antonia Banyard
    • , Philippa Middlehurst
    • , Jeff Barry
    • , Sarah Mills
    • , Zena Salih
    • , John Weightman
    • , Avinash Gupta
    • , Gabriela Gremel
    • , Franziska Baenke
    • , Nathalie Dhomen
    • , Paul C. Lorigan
    •  & Richard Marais
  • Publisher Correction |

    • Gabriel Abril-Rodriguez
    • , Davis Y. Torrejon
    • , Wei Liu
    • , Jesse M. Zaretsky
    • , Theodore S. Nowicki
    • , Jennifer Tsoi
    • , Cristina Puig-Saus
    • , Ignacio Baselga-Carretero
    • , Egmidio Medina
    • , Michael J. Quist
    • , Alejandro J. Garcia
    • , William Senapedis
    • , Erkan Baloglu
    • , Anusha Kalbasi
    • , Gardenia Cheung-Lau
    • , Beata Berent-Maoz
    • , Begoña Comin-Anduix
    • , Siwen Hu-Lieskovan
    • , Cun-Yu Wang
    • , Catherine S. Grasso
    •  & Antoni Ribas
  • Article |

    Diehn and colleagues report that assaying circulating DNA in patients receiving chemoradiation therapy for non-small-cell lung cancer could identify the patients most likely to benefit from consolidation immunotherapy.

    • Everett J. Moding
    • , Yufei Liu
    • , Barzin Y. Nabet
    • , Jacob J. Chabon
    • , Aadel A. Chaudhuri
    • , Angela B. Hui
    • , Rene F. Bonilla
    • , Ryan B. Ko
    • , Christopher H. Yoo
    • , Linda Gojenola
    • , Carol D. Jones
    • , Jianzhong He
    • , Yawei Qiao
    • , Ting Xu
    • , John V. Heymach
    • , Anne Tsao
    • , Zhongxing Liao
    • , Daniel R. Gomez
    • , Millie Das
    • , Sukhmani K. Padda
    • , Kavitha J. Ramchandran
    • , Joel W. Neal
    • , Heather A. Wakelee
    • , Billy W. Loo Jr
    • , Steven H. Lin
    • , Ash A. Alizadeh
    •  & Maximilian Diehn
  • Article |

    Cong et al. show that MTSS1 suppresses breast cancer initiation by promoting ubiquitin-mediated suppression of the NF-κB pathway. Loss of this regulatory mechanism promotes the activation and expansion of tumor-initiating cells.

    • Min Cong
    • , Yuan Wang
    • , Yang Yang
    • , Cheng Lian
    • , Xueqian Zhuang
    • , Xiaoxun Li
    • , Peiyuan Zhang
    • , Yingjie Liu
    • , Jun Tang
    • , Qifeng Yang
    • , Xue Zhang
    • , Hua Xiong
    • , Ronggui Hu
    •  & Guohong Hu
  • Resource |

    Golub and colleagues tested thousands of drugs not originally developed for oncology across 578 human cancer cell lines, revealing growth-inhibitory effects and providing a resource to identify drugs with the potential to be repurposed for cancer.

    • Steven M. Corsello
    • , Rohith T. Nagari
    • , Ryan D. Spangler
    • , Jordan Rossen
    • , Mustafa Kocak
    • , Jordan G. Bryan
    • , Ranad Humeidi
    • , David Peck
    • , Xiaoyun Wu
    • , Andrew A. Tang
    • , Vickie M. Wang
    • , Samantha A. Bender
    • , Evan Lemire
    • , Rajiv Narayan
    • , Philip Montgomery
    • , Uri Ben-David
    • , Colin W. Garvie
    • , Yejia Chen
    • , Matthew G. Rees
    • , Nicholas J. Lyons
    • , James M. McFarland
    • , Bang T. Wong
    • , Li Wang
    • , Nancy Dumont
    • , Patrick J. O’Hearn
    • , Eric Stefan
    • , John G. Doench
    • , Caitlin N. Harrington
    • , Heidi Greulich
    • , Matthew Meyerson
    • , Francisca Vazquez
    • , Aravind Subramanian
    • , Jennifer A. Roth
    • , Joshua A. Bittker
    • , Jesse S. Boehm
    • , Christopher C. Mader
    • , Aviad Tsherniak
    •  & Todd R. Golub
  • Article |

    Kupper and colleagues introduce the T-cell fraction as a molecular assessment of T-cell-mediated antitumor responses in primary melanomas that can predict metastatic recurrence.

    • Wiebke Pruessmann
    • , Julie Rytlewski
    • , James Wilmott
    • , Martin C. Mihm Jr
    • , Grace H. Attrill
    • , Beatrice Dyring-Andersen
    • , Paul Fields
    • , Qian Zhan
    • , Andrew J. Colebatch
    • , Peter M. Ferguson
    • , John F. Thompson
    • , Klaus Kallenbach
    • , Erik Yusko
    • , Rachael A. Clark
    • , Harlan Robins
    • , Richard A. Scolyer
    •  & Thomas S. Kupper
  • Article |

    Anagnostou et al. present an improved predictor of response to immune checkpoint blockade that integrates estimates of tumor mutational burden corrected for tumor purity, RTK genomic alterations, a smoking-related mutational signature and HLA status.

    • Valsamo Anagnostou
    • , Noushin Niknafs
    • , Kristen Marrone
    • , Daniel C. Bruhm
    • , James R. White
    • , Jarushka Naidoo
    • , Karlijn Hummelink
    • , Kim Monkhorst
    • , Ferry Lalezari
    • , Mara Lanis
    • , Samuel Rosner
    • , Joshua E. Reuss
    • , Kellie N. Smith
    • , Vilmos Adleff
    • , Kristen Rodgers
    • , Zineb Belcaid
    • , Lamia Rhymee
    • , Benjamin Levy
    • , Josephine Feliciano
    • , Christine L. Hann
    • , David S. Ettinger
    • , Christos Georgiades
    • , Franco Verde
    • , Peter Illei
    • , Qing Kay Li
    • , Alexander S. Baras
    • , Edward Gabrielson
    • , Malcolm V. Brock
    • , Rachel Karchin
    • , Drew M. Pardoll
    • , Stephen B. Baylin
    • , Julie R. Brahmer
    • , Robert B. Scharpf
    • , Patrick M. Forde
    •  & Victor E. Velculescu
  • Article |

    Iacobuzio-Donahue and colleagues use integrated transcriptomic, histologic and mutational data to analyze squamous features of pancreatic ductal adenocarcinoma (PDAC), further refining the understanding of heterogeneity and evolution in PDAC.

    • Akimasa Hayashi
    • , Jun Fan
    • , Ruoyao Chen
    • , Yu-jui Ho
    • , Alvin P. Makohon-Moore
    • , Nicolas Lecomte
    • , Yi Zhong
    • , Jungeui Hong
    • , Jinlong Huang
    • , Hitomi Sakamoto
    • , Marc A. Attiyeh
    • , Zachary A. Kohutek
    • , Lance Zhang
    • , Aida Boumiza
    • , Rajya Kappagantula
    • , Priscilla Baez
    • , Jessica Bai
    • , Marta Lisi
    • , Kalyani Chadalavada
    • , Jerry P. Melchor
    • , Winston Wong
    • , Gouri J. Nanjangud
    • , Olca Basturk
    • , Eileen M. O’Reilly
    • , David S. Klimstra
    • , Ralph H. Hruban
    • , Laura D. Wood
    • , Michael Overholtzer
    •  & Christine A. Iacobuzio-Donahue
  • Article |

    Ajona and colleagues report that short-term starvation synergizes with anti-PD-1 blockade to reduce lung tumor growth and metastasis. This antitumor effect is mediated through the reduction of plasma IGF-1 levels and IGF-1R levels on tumor cells.

    • Daniel Ajona
    • , Sergio Ortiz-Espinosa
    • , Teresa Lozano
    • , Francisco Exposito
    • , Alfonso Calvo
    • , Karmele Valencia
    • , Miriam Redrado
    • , Ana Remírez
    • , Fernando Lecanda
    • , Diego Alignani
    • , Juan J. Lasarte
    • , Irati Macaya
    • , Yaiza Senent
    • , Cristina Bértolo
    • , Cristina Sainz
    • , Ignacio Gil-Bazo
    • , Iñaki Eguren-Santamaría
    • , Jose M. Lopez-Picazo
    • , Alvaro Gonzalez
    • , Jose L. Perez-Gracia
    • , Carlos E. de Andrea
    • , Silvestre Vicent
    • , Miguel F. Sanmamed
    • , Luis M. Montuenga
    •  & Ruben Pio
  • Article |

    The authors identify a population of L1CAM-positive cells that, following loss of epithelial integrity, promote intestinal tissue regeneration and mediate metastasis initiation and chemoresistance in colorectal cancer.

    • Karuna Ganesh
    • , Harihar Basnet
    • , Yasemin Kaygusuz
    • , Ashley M. Laughney
    • , Lan He
    • , Roshan Sharma
    • , Kevin P. O’Rourke
    • , Vincent P. Reuter
    • , Yun-Han Huang
    • , Mesruh Turkekul
    • , Ekrem Emrah Er
    • , Ignas Masilionis
    • , Katia Manova-Todorova
    • , Martin R. Weiser
    • , Leonard B. Saltz
    • , Julio Garcia-Aguilar
    • , Richard Koche
    • , Scott W. Lowe
    • , Dana Pe’er
    • , Jinru Shia
    •  & Joan Massagué
  • Article |

    Ribas and colleagues report that inhibition of PAK4 improves response to anti-PD-1 immunotherapy by reducing Wnt pathway activation and increasing tumor infiltration by T cells.

    • Gabriel Abril-Rodriguez
    • , Davis Y. Torrejon
    • , Wei Liu
    • , Jesse M. Zaretsky
    • , Theodore S. Nowicki
    • , Jennifer Tsoi
    • , Cristina Puig-Saus
    • , Ignacio Baselga-Carretero
    • , Egmidio Medina
    • , Michael J. Quist
    • , Alejandro J. Garcia
    • , William Senapedis
    • , Erkan Baloglu
    • , Anusha Kalbasi
    • , Gardenia Cheung-Lau
    • , Beata Berent-Maoz
    • , Begoña Comin-Anduix
    • , Siwen Hu-Lieskovan
    • , Cun-Yu Wang
    • , Catherine S. Grasso
    •  & Antoni Ribas
  • Analysis |

    Martínez-Jiménez et al. report how disruption of the ubiquitin–proteasome system affects cancer, estimating that >10% of driver mutations involve alterations in genes relevant in ubiquitin-mediated proteolysis, including E3 ligases and their targets.

    • Francisco Martínez-Jiménez
    • , Ferran Muiños
    • , Erika López-Arribillaga
    • , Nuria Lopez-Bigas
    •  & Abel Gonzalez-Perez
  • Article |

    Wu et al. develop trispecific antibodies that recognize CD38, CD3 and CD28 and induce T cell activation and co-signaling. They show in mice and non-human primates that by engaging multiple targets, these antibodies induce enhanced tumor-cell killing.

    • Lan Wu
    • , Edward Seung
    • , Ling Xu
    • , Ercole Rao
    • , Dana M. Lord
    • , Ronnie R. Wei
    • , Virna Cortez-Retamozo
    • , Beatriz Ospina
    • , Valeriya Posternak
    • , Gregory Ulinski
    • , Peter Piepenhagen
    • , Elisa Francesconi
    • , Nizar El-Murr
    • , Christian Beil
    • , Patrick Kirby
    • , Aiqun Li
    • , Jennifer Fretland
    • , Rita Vicente
    • , Gejing Deng
    • , Tarik Dabdoubi
    • , Beatrice Cameron
    • , Thomas Bertrand
    • , Paul Ferrari
    • , Stéphanie Pouzieux
    • , Cendrine Lemoine
    • , Catherine Prades
    • , Anna Park
    • , Huawei Qiu
    • , Zhili Song
    • , Bailin Zhang
    • , Fangxian Sun
    • , Marielle Chiron
    • , Srinivas Rao
    • , Katarina Radošević
    • , Zhi-yong Yang
    •  & Gary J. Nabel