Browse Articles

  • Viewpoint |

    Filtered through the analytical power of artificial intelligence, the wealth of available biomedical data promises to revolutionize cancer research, diagnosis and care. In this Viewpoint, six experts discuss some of the challenges, exciting developments and future questions arising at the interface of machine learning and oncology.

    • Olga Troyanskaya
    • , Zlatko Trajanoski
    • , Anne Carpenter
    • , Sebastian Thrun
    • , Narges Razavian
    •  & Nuria Oliver
  • Editorial |

    The convergence of big data and artificial intelligence is poised to revolutionize cancer research and care, from basic conceptual developments to translational and clinical applications. To reap these benefits, it is important to separate the hope from the hype.

  • Article |

    Li and colleagues report that extracellular cGAMP produced by cancer cells acts as an immunotransmitter that, when combined with ionizing radiation, can reduce tumor volume.

    • Jacqueline A. Carozza
    • , Volker Böhnert
    • , Khanh C. Nguyen
    • , Gemini Skariah
    • , Kelsey E. Shaw
    • , Jenifer A. Brown
    • , Marjan Rafat
    • , Rie von Eyben
    • , Edward E. Graves
    • , Jeffrey S. Glenn
    • , Mark Smith
    •  & Lingyin Li
  • Q&A |

    Zena Werb is Professor and Vice Chair of the Department of Anatomy at the University of California at San Francisco and Associate Director for Basic Science of the UCSF Helen Diller Family Comprehensive Cancer Center. Nature Cancer caught up with her at the 6th International Conference on Tumor Microenvironment and Cellular Stress organized by Aegean Conferences and held in Greece in the fall of 2019, to talk about her career and work in the tumor microenvironment field.

    • Alexia-Ileana Zaromytidou
  • 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
  • News & Views |

    Tumor heterogeneity remains an obstacle to effective clinical management of breast cancer. Two new studies use high-dimensional imaging of single-cell protein expression in situ in clinical samples to link genomic alterations to multi-cellular features of the tumor microenvironment and reveal breast-cancer phenotypes associated with clinical outcome.

    • Leeat Keren
    •  & Michael Angelo
  • Comment |

    Low- and middle-income countries share the greatest burden of cancer mortality globally but lag behind high-income countries in terms of clinical trials. Here we discuss the challenges facing low- and middle-income countries and the opportunities for conducting trials of affordable, accessible and effective interventions relevant to the local population.

    • Bishal Gyawali
    • , Gauthier Bouche
    • , Nigel Crisp
    •  & Nicolas André
  • 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
  • News & Views |

    Discerning and analyzing the mutational patterns that arise in the cancer genome can provide essential information on the process of tumorigenesis. An analytical framework and web-based tool now aim to aid in mutational signature assignment for improved tumor stratification.

    • Giovanni Ciriello
  • News & Views |

    Identifying indicators of response to immunotherapy is key for treatment decisions. Two studies now report that early changes in T cell repertoires and CD8+ memory effector cytotoxic T cells in peripheral blood correlate with response to immune-checkpoint inhibitors in metastatic melanoma and may serve as actionable biomarkers of immune activation.

    • Genevieve M. Boland
    •  & Keith T. Flaherty
  • 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
  • News & Views |

    Drug repurposing is an attractive strategy for extending the arsenal of oncology therapies. Screening of a large collection of existing non-oncology compounds against a panel of cancer cell lines now identifies several drugs capable of selectively inhibiting the growth of cancer cells.

    • Roderick L. Beijersbergen
  • 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
  • Comment |

    By integrating discovery science with clinical practice and therapeutic intervention, clinician-scientists fulfil a unique role in cancer research. However, their numbers are in decline, which is creating the need for flexible training and research opportunities to ensure their future.

    • Karen Noble
    • , Joanna Owens
    • , Fabrice André
    • , Samuel F. Bakhoum
    • , Sherene Loi
    • , Hans Christian Reinhardt
    • , David Tuveson
    •  & Charles Swanton
  • 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
  • News & Views |

    Identifying cancer driver mutations is essential to understand disease biology and devise effective therapies, but remains a complex endeavor. A focused analytical approach is now presented that defines driver mutations affecting ubiquitin-mediated proteolysis through machine learning and mining of cancer multi-omics data.

    • Han Liang
  • Q&A |

    Norman E. ‘Ned’ Sharpless became director of the US National Cancer Institute (NCI) in 2017. From April 2019, he served as acting commissioner of the US Food and Drug Administration (FDA), and he returned to the NCI in November. Douglas R. Lowy has been the principal deputy director of the NCI since 2010, having also served as acting director twice, most recently in 2019. Nature Cancer spoke with both last fall to learn more about what makes NCI and its leadership tick.

    • Alexia-Ileana Zaromytidou
  • Comment |

    Intratumoral genetic heterogeneity of driver somatic mutations is present in a variety of tumor types, yet the extent of heterogeneity is variable. We propose that this variation is a reflection of the inherent biology of a given tumor type, representing the pace of metastatic dissemination and hence clinical disease course.

    • Christine A. Iacobuzio-Donahue
    • , Kevin Litchfield
    •  & Charles Swanton
  • 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
  • Viewpoint |

    Cancer research in recent years has been marked by significant developments in understanding disease biology and foundational discoveries that have changed clinical practice. Ten cancer researchers take stock of the field, the advances that excite them, key outstanding questions and breakthroughs they anticipate looking forward.

    • René Bernards
    • , Elizabeth Jaffee
    • , Johanna A. Joyce
    • , Scott W. Lowe
    • , Elaine R. Mardis
    • , Sean J. Morrison
    • , Kornelia Polyak
    • , Cynthia L. Sears
    • , Karen H. Vousden
    •  & Zemin Zhang
  • News & Views |

    Metastasis competence can be acquired early in tumorigenesis, although its underlying molecular intricacies remain unclear. A recent study provides key information about the function of L1CAM in conferring metastasis-initiation potential and chemoresistance in colorectal cancer by hijacking epithelial regenerative mechanisms.

    • Gloria Pascual
    •  & Salvador A. Benitah
  • News & Views |

    Immunotherapy resistance is associated with poor T cell infiltration into tumors. Tumor-cell-intrinsic oncogenic events that contribute to this defect include Wnt–β-catenin activation. PAK4 is now identified as an upstream modulator of this pathway, thus suggesting the potential of enhancing the efficacy of immunotherapy by targeting this druggable kinase.

    • Thomas F. Gajewski
    •  & Jessica Fessler
  • 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
  • Cancer in Translation |

    KRAS mutations are among the most prevalent tumor drivers, but targeting them pharmacologically has been challenging. Recent landmark studies have demonstrated promising clinical results of KRASG12C inhibition by using small molecules. Bar-Sagi, and Knelson and Sequist provide their distinct perspectives on this recent tour de force in targeting KRASG12C alterations.

    • Dafna Bar-Sagi
    • , Erik H. Knelson
    •  & Lecia V. Sequist
  • Editorial |

    Cancer is a multifaceted global health issue that continues to demand action. We are launching Nature Cancer to inform, inspire and convene scientists across the multidisciplinary arena of cancer research, aiming to advance biomedical knowledge and treatment strategies within the greater framework of society.

  • 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