Cancer

  • Article | | open

    Triple negative breast cancers (TNBC) disseminate and metastasise, but the clonal relationship of metastases to primary tumours is poorly understood. Here, the authors use cellular barcoding of TNBC patient-derived xenografts and track the fate of barcoded clones in primary tumours and their metastases, including after resection or chemotherapy.

    • D. Merino
    • , T. S. Weber
    • , A. Serrano
    • , F. Vaillant
    • , K. Liu
    • , B. Pal
    • , L. Di Stefano
    • , J. Schreuder
    • , D. Lin
    • , Y. Chen
    • , M. L. Asselin-Labat
    • , T. N. Schumacher
    • , D. Cameron
    • , G. K. Smyth
    • , A. T. Papenfuss
    • , G. J. Lindeman
    • , J. E. Visvader
    •  & S. H. Naik
  • Article | | open

    Radiomics—the quantification of features within tumor images—has shown prognostic potential in cancer. Here, the authors use a machine learning approach to develop a radiomic-based small set of descriptors to predict ovarian cancer patient survival based on CT scans acquired pre-operatively in 364 patients.

    • Haonan Lu
    • , Mubarik Arshad
    • , Andrew Thornton
    • , Giacomo Avesani
    • , Paula Cunnea
    • , Ed Curry
    • , Fahdi Kanavati
    • , Jack Liang
    • , Katherine Nixon
    • , Sophie T. Williams
    • , Mona Ali Hassan
    • , David D. L. Bowtell
    • , Hani Gabra
    • , Christina Fotopoulou
    • , Andrea Rockall
    •  & Eric O. Aboagye
  • Article | | open

    Whether the Wnt enhanceosome’ components BCL9/9l can affect intestinal homeostasis and tumorigenesis is still unclear. Using conditional Bcl9/9l KO mice, the authors of this study show that the BCL9/9l complex is required for intestinal stem cells to drive tissue regeneration and that loss of BCL9/9l suppresses Wnt-driven transformation.

    • David M. Gay
    • , Rachel A. Ridgway
    • , Miryam Müeller
    • , Michael C. Hodder
    • , Ann Hedley
    • , William Clark
    • , Joshua D. Leach
    • , Rene Jackstadt
    • , Colin Nixon
    • , David J. Huels
    • , Andrew D. Campbell
    • , Thomas G. Bird
    •  & Owen J. Sansom
  • Article | | open

    BCL9 and Pygo are components of Wnt enhanceosome, which facilitates β-catenin-dependent transcription. Here, the authors show that deletion of Bcl9 and Pygo suppresses tumorigenesis and extends disease free survival in two different colorectal cancer models, suggesting a strategy for drugging β-catenin signalling in this cancer.

    • Juliusz Mieszczanek
    • , Laurens M. van Tienen
    • , Ashraf E. K. Ibrahim
    • , Douglas J. Winton
    •  & Mariann Bienz
  • Article | | open

    Targeting histone acetylation modulators (HAMPs) is a promising avenue of drug discovery in cancer research. Here, the authors integrate multi-dimensional genomic profiles to systematically investigate recurrent genomic alterations in HAMPs, identifying potential therapeutic targets for precision epigenetic treatment.

    • Zhongyi Hu
    • , Junzhi Zhou
    • , Junjie Jiang
    • , Jiao Yuan
    • , Youyou Zhang
    • , Xuepeng Wei
    • , Nicki Loo
    • , Yueying Wang
    • , Yutian Pan
    • , Tianli Zhang
    • , Xiaomin Zhong
    • , Meixiao Long
    • , Kathleen T. Montone
    • , Janos L. Tanyi
    • , Yi Fan
    • , Tian-Li Wang
    • , Ie-Ming Shih
    • , Xiaowen Hu
    •  & Lin Zhang
  • Article | | open

    Bladder cancer is one of the most common and highly vascularized cancers. Here the authors perform a whole-genome analysis in urothelial bladder carcinomas and identify recurrent genetic alterations in a set of angiogenesis genes, facilitating the understanding of molecular mechanisms underlying pathological angiogenesis in this type of cancer.

    • Song Wu
    • , Tong Ou
    • , Nianzeng Xing
    • , Jiang Lu
    • , Shengqing Wan
    • , Changxi Wang
    • , Xi Zhang
    • , Feiya Yang
    • , Yi Huang
    •  & Zhiming Cai
  • Article | | open

    Loss of PIK3R1 in ovarian cancer is a common event, which provides opportunities for therapeutic intervention. Here, the authors show that the STAT3 and AKT signaling pathways are activated upon PIK3R1 loss and that, in mice, inhibitors of these pathways could block tumorigenesis.

    • Xinran Li
    • , Victor C. Y. Mak
    • , Yuan Zhou
    • , Chao Wang
    • , Esther S. Y. Wong
    • , Rakesh Sharma
    • , Yiling Lu
    • , Annie N. Y. Cheung
    • , Gordon B. Mills
    •  & Lydia W. T. Cheung
  • Article | | open

    Cancer cells respond differently to inhibitors of Poly (ADP-ribose) polymerase. Here the authors reveal that ovarian cancer cells with higher cellular NADP+ levels are more sensitive to clinically relevant PARP1 inhibitors and show that NADP+ act as an endogenous inhibitor of PARP enzymes.

    • Chunjing Bian
    • , Chao Zhang
    • , Tao Luo
    • , Aditi Vyas
    • , Shih-Hsun Chen
    • , Chao Liu
    • , Muzaffer Ahmad Kassab
    • , Ying Yang
    • , Mei Kong
    •  & Xiaochun Yu
  • Article | | open

    When examining the evolution of treatment resistance in breast cancer, perceived genomic changes may be due to clonal evolution or heterogeneous tumors. Here, the authors show that apparent clonal change can in fact be due to pre-treatment heterogeneity, and samples from at least two regions are necessary to detect treatment-induced clonal shifts

    • Jennifer L. Caswell-Jin
    • , Katherine McNamara
    • , Johannes G. Reiter
    • , Ruping Sun
    • , Zheng Hu
    • , Zhicheng Ma
    • , Jie Ding
    • , Carlos J. Suarez
    • , Susanne Tilk
    • , Akshara Raghavendra
    • , Victoria Forte
    • , Suet-Feung Chin
    • , Helen Bardwell
    • , Elena Provenzano
    • , Carlos Caldas
    • , Julie Lang
    • , Robert West
    • , Debu Tripathy
    • , Michael F. Press
    •  & Christina Curtis
  • Article | | open

    MicroRNA miR-500a-5p has been linked to oncogenesis but its role in colorectal cancer (CRC) is largely unknown. Here, the authors investigate the role of miR-500a-5p in CRC in vitro and in vivo models and find that miR-500a-5p acts as a tumour suppressor in CRC by targeting the p300/YY1/HDAC2 axis.

    • Weimei Tang
    • , Weijie Zhou
    • , Li Xiang
    • , Xiaosheng Wu
    • , Pei Zhang
    • , Jing Wang
    • , Guangnan Liu
    • , Wenjing Zhang
    • , Ying Peng
    • , Xiaoting Huang
    • , Jianqun Cai
    • , Yang Bai
    • , Lan Bai
    • , Wei Zhu
    • , Hongxiang Gu
    • , Jing Xiong
    • , Chen Ye
    • , Aimin Li
    • , Side Liu
    •  & Jide Wang
  • Article | | open

    Capicua (CIC) is a tumour suppressor in oligodendroglioma. Here, the authors show that ERK activation mediates CIC regulation via ubiquitination and degradation by PJA1 and a degradation resistant form of CIC enhances efficacy of ERK inhibition in glioblastoma.

    • Severa Bunda
    • , Pardeep Heir
    • , Julie Metcalf
    • , Annie Si Cong Li
    • , Sameer Agnihotri
    • , Stefan Pusch
    • , Mamatjan Yasin
    • , Mira Li
    • , Kelly Burrell
    • , Sheila Mansouri
    • , Olivia Singh
    • , Mark Wilson
    • , Amir Alamsahebpour
    • , Romina Nejad
    • , Bethany Choi
    • , David Kim
    • , Andreas von Deimling
    • , Gelareh Zadeh
    •  & Kenneth Aldape
  • Article | | open

    PTEN is a lipid phosphatase that functions as a dose-dependent tumor suppressor through the PI3K/AKT pathway. Here the authors describe a signaling feedback mechanism where PTEN stability is regulated through transcriptional upregulation of X-linked ubiquitin-specific protease 11 (USP11) via the PI3K/FOXO pathway.

    • Mi Kyung Park
    • , Yixin Yao
    • , Weiya Xia
    • , Stephanie Rebecca Setijono
    • , Jae Hwan Kim
    • , Isabelle K. Vila
    • , Hui-Hsuan Chiu
    • , Yun Wu
    • , Enrique González Billalabeitia
    • , Min Gyu Lee
    • , Robert G. Kalb
    • , Mien-Chie Hung
    • , Pier Paolo Pandolfi
    • , Su Jung Song
    •  & Min Sup Song
  • Article | | open

    Elevated MYC levels can sensitize tumor cells to apoptosis. In this study, the authors demonstrate that AMPK activation and BCL-2/BCL-XL inhibition have a synergistic effect on apoptosis, and that together with anti PD-1 therapy they can suppress Myc-driven mammary tumor growth.

    • Heidi M. Haikala
    • , Johanna M. Anttila
    • , Elsa Marques
    • , Tiina Raatikainen
    • , Mette Ilander
    • , Henna Hakanen
    • , Hanna Ala-Hongisto
    • , Mariel Savelius
    • , Diego Balboa
    • , Bjoern Von Eyss
    • , Vilja Eskelinen
    • , Pauliina Munne
    • , Anni I. Nieminen
    • , Timo Otonkoski
    • , Julia Schüler
    • , Teemu D. Laajala
    • , Tero Aittokallio
    • , Harri Sihto
    • , Johanna Mattson
    • , Päivi Heikkilä
    • , Marjut Leidenius
    • , Heikki Joensuu
    • , Satu Mustjoki
    • , Panu Kovanen
    • , Martin Eilers
    • , Joel D. Leverson
    •  & Juha Klefström
  • Article | | open

    Non-small cell lung cancers with inactivating SMARCA4 mutations are currently undruggable. Here, the authors show that the absence of SMARCA4/2 reduces chromatin accessibility at the CCND1 locus, leading to a subsequent reduction in cyclin D1 expression, which promotes vulnerability of these cancers to CDK4/6 inhibition.

    • Yibo Xue
    • , Brian Meehan
    • , Zheng Fu
    • , Xue Qing D. Wang
    • , Pierre Olivier Fiset
    • , Ralf Rieker
    • , Cameron Levins
    • , Tim Kong
    • , Xianbing Zhu
    • , Geneviève Morin
    • , Lashanda Skerritt
    • , Esther Herpel
    • , Sriram Venneti
    • , Daniel Martinez
    • , Alexander R. Judkins
    • , Sungmi Jung
    • , Sophie Camilleri-Broet
    • , Anne V. Gonzalez
    • , Marie-Christine Guiot
    • , William W. Lockwood
    • , Jonathan D. Spicer
    • , Abbas Agaimy
    • , William A. Pastor
    • , Josée Dostie
    • , Janusz Rak
    • , William D. Foulkes
    •  & Sidong Huang
  • Article | | open

    Small cell carcinoma of the ovary, hypercalcemic type (SCCOHT) is driven by SMARCA4 loss. Here the authors demonstrate that SCCOHT cells are highly sensitive to CDK4/6 inhibition and provide mechanistic insights, whereby this druggable vulnerability is driven by cyclin D1 deficiency induced by SMARCA4 loss.

    • Yibo Xue
    • , Brian Meehan
    • , Elizabeth Macdonald
    • , Sriram Venneti
    • , Xue Qing D. Wang
    • , Leora Witkowski
    • , Petar Jelinic
    • , Tim Kong
    • , Daniel Martinez
    • , Geneviève Morin
    • , Michelle Firlit
    • , Atefeh Abedini
    • , Radia M. Johnson
    • , Regina Cencic
    • , Jay Patibandla
    • , Hongbo Chen
    • , Andreas I. Papadakis
    • , Aurelie Auguste
    • , Iris de Rink
    • , Ron M. Kerkhoven
    • , Nicholas Bertos
    • , Walter H. Gotlieb
    • , Blaise A. Clarke
    • , Alexandra Leary
    • , Michael Witcher
    • , Marie-Christine Guiot
    • , Jerry Pelletier
    • , Josée Dostie
    • , Morag Park
    • , Alexander R. Judkins
    • , Ralf Hass
    • , Douglas A. Levine
    • , Janusz Rak
    • , Barbara Vanderhyden
    • , William D. Foulkes
    •  & Sidong Huang
  • Article | | open

    The immunosuppressive tumor environment and the lack of functional anti-tumor immunity are major limiting factors in immunotherapy. Here the authors show that human and mouse tumors are infiltrated by virus-specific memory T cells, which can be harnessed by viral peptides to induce local and systemic anti-tumor immunity and synergize with checkpoint blockade.

    • Pamela C. Rosato
    • , Sathi Wijeyesinghe
    • , J. Michael Stolley
    • , Christine E. Nelson
    • , Rachel L. Davis
    • , Luke S. Manlove
    • , Christopher A. Pennell
    • , Bruce R. Blazar
    • , Clark C. Chen
    • , Melissa A. Geller
    • , Vaiva Vezys
    •  & David Masopust
  • Article | | open

    CD47 is a promising new target in cancer immunotherapy and recently the pro-phagocytic signal SLAMF7 has been shown to have a crucial role in phagocytosis induced by CD47-blocking antibody in hematological tumors. In this study, the authors demonstrate that SLAMF7 expressed by cancer cells is not required for phagocytosis suggesting that, in contrast to CD47 expression, SLAMF7 should not be used as selection criterion for CD47-targeted therapy.

    • Yuan He
    • , Renee Bouwstra
    • , Valerie R. Wiersma
    • , Mathilde de Jong
    • , Harm Jan Lourens
    • , Rudolf Fehrmann
    • , Marco de Bruyn
    • , Emanuele Ammatuna
    • , Gerwin Huls
    • , Tom van Meerten
    •  & Edwin Bremer
  • Article | | open

    Fibrinogen-like protein 2 (FGL2) mediates immune suppression in glioblastoma (GBM). Here, the authors show that FGL-2 expressed by GBM cancer cells acts by suppressing the differentiation of CD103+ DC cells required to activate the anti-tumor CD8+ T cell response via blocking GM-CSF signalling at NFKB, STAT1/5 and p38 level.

    • Jun Yan
    • , Qingnan Zhao
    • , Konrad Gabrusiewicz
    • , Ling-Yuan Kong
    • , Xueqing Xia
    • , Jian Wang
    • , Martina Ott
    • , Jingda Xu
    • , R. Eric Davis
    • , Longfei Huo
    • , Ganesh Rao
    • , Shao-Cong Sun
    • , Stephanie S. Watowich
    • , Amy B. Heimberger
    •  & Shulin Li
  • Article | | open

    The delivery of single therapeutic microRNAs in brain cancers is challenging. Here, the authors engineer three neuronal microRNAs (miR-124, 128 and 137) into a cluster that, targeting oncogenic chromatin repressors, increases survival of GBM-bearing mice when combined with chemotherapy.

    • Vivek Bhaskaran
    • , Michal O. Nowicki
    • , Mahmoud Idriss
    • , Miguel A. Jimenez
    • , Gianmarco Lugli
    • , Josie L. Hayes
    • , Ahmad Bakur Mahmoud
    • , Rachel E. Zane
    • , Carmela Passaro
    • , Keith L. Ligon
    • , Daphne Haas-Kogan
    • , Agnieszka Bronisz
    • , Jakub Godlewski
    • , Sean E. Lawler
    • , E. Antonio Chiocca
    •  & Pierpaolo Peruzzi
  • Article | | open

    Adoptive cell therapy (ACT) using neoantigen-specific T cells can lead to tumor regression. Here the authors use an in vitro stimulation approach to isolate tumor specific memory T cells from peripheral blood of metastatic epithelial cancer patients targeting unique as well as shared mutations in the KRAS oncogene.

    • Gal Cafri
    • , Rami Yossef
    • , Anna Pasetto
    • , Drew C. Deniger
    • , Yong-Chen Lu
    • , Maria Parkhurst
    • , Jared J. Gartner
    • , Li Jia
    • , Satyajit Ray
    • , Lien T. Ngo
    • , Mohammad Jafferji
    • , Abraham Sachs
    • , Todd Prickett
    • , Paul F. Robbins
    •  & Steven A. Rosenberg
  • Article | | open

    Similarities in cancers can be studied to interrogate their etiology. Here, the authors use genome-wide association study summary statistics from six cancer types based on 296,215 cases and 301,319 controls of European ancestry, showing that solid tumours arising from different tissues share a degree of common germline genetic basis.

    • Xia Jiang
    • , Hilary K. Finucane
    • , Fredrick R. Schumacher
    • , Stephanie L. Schmit
    • , Jonathan P. Tyrer
    • , Younghun Han
    • , Kyriaki Michailidou
    • , Corina Lesseur
    • , Karoline B. Kuchenbaecker
    • , Joe Dennis
    • , David V. Conti
    • , Graham Casey
    • , Mia M. Gaudet
    • , Jeroen R. Huyghe
    • , Demetrius Albanes
    • , Melinda C. Aldrich
    • , Angeline S. Andrew
    • , Irene L. Andrulis
    • , Hoda Anton-Culver
    • , Antonis C. Antoniou
    • , Natalia N. Antonenkova
    • , Susanne M. Arnold
    • , Kristan J. Aronson
    • , Banu K. Arun
    • , Elisa V. Bandera
    • , Rosa B. Barkardottir
    • , Daniel R. Barnes
    • , Jyotsna Batra
    • , Matthias W. Beckmann
    • , Javier Benitez
    • , Sara Benlloch
    • , Andrew Berchuck
    • , Sonja I. Berndt
    • , Heike Bickeböller
    • , Stephanie A. Bien
    • , Carl Blomqvist
    • , Stefania Boccia
    • , Natalia V. Bogdanova
    • , Stig E. Bojesen
    • , Manjeet K. Bolla
    • , Hiltrud Brauch
    • , Hermann Brenner
    • , James D. Brenton
    • , Mark N. Brook
    • , Joan Brunet
    • , Hans Brunnström
    • , Daniel D. Buchanan
    • , Barbara Burwinkel
    • , Ralf Butzow
    • , Gabriella Cadoni
    • , Trinidad Caldés
    • , Maria A. Caligo
    • , Ian Campbell
    • , Peter T. Campbell
    • , Géraldine Cancel-Tassin
    • , Lisa Cannon-Albright
    • , Daniele Campa
    • , Neil Caporaso
    • , André L. Carvalho
    • , Andrew T. Chan
    • , Jenny Chang-Claude
    • , Stephen J. Chanock
    • , Chu Chen
    • , David C. Christiani
    • , Kathleen B. M. Claes
    • , Frank Claessens
    • , Judith Clements
    • , J. Margriet Collée
    • , Marcia Cruz Correa
    • , Fergus J. Couch
    • , Angela Cox
    • , Julie M. Cunningham
    • , Cezary Cybulski
    • , Kamila Czene
    • , Mary B. Daly
    • , Anna deFazio
    • , Peter Devilee
    • , Orland Diez
    • , Manuela Gago-Dominguez
    • , Jenny L. Donovan
    • , Thilo Dörk
    • , Eric J. Duell
    • , Alison M. Dunning
    • , Miriam Dwek
    • , Diana M. Eccles
    • , Christopher K. Edlund
    • , Digna R Velez Edwards
    • , Carolina Ellberg
    • , D. Gareth Evans
    • , Peter A. Fasching
    • , Robert L. Ferris
    • , Triantafillos Liloglou
    • , Jane C. Figueiredo
    • , Olivia Fletcher
    • , Renée T. Fortner
    • , Florentia Fostira
    • , Silvia Franceschi
    • , Eitan Friedman
    • , Steven J. Gallinger
    • , Patricia A. Ganz
    • , Judy Garber
    • , José A. García-Sáenz
    • , Simon A. Gayther
    • , Graham G. Giles
    • , Andrew K. Godwin
    • , Mark S. Goldberg
    • , David E. Goldgar
    • , Ellen L. Goode
    • , Marc T. Goodman
    • , Gary Goodman
    • , Kjell Grankvist
    • , Mark H. Greene
    • , Henrik Gronberg
    • , Jacek Gronwald
    • , Pascal Guénel
    • , Niclas Håkansson
    • , Per Hall
    • , Ute Hamann
    • , Freddie C. Hamdy
    • , Robert J. Hamilton
    • , Jochen Hampe
    • , Aage Haugen
    • , Florian Heitz
    • , Rolando Herrero
    • , Peter Hillemanns
    • , Michael Hoffmeister
    • , Estrid Høgdall
    • , Yun-Chul Hong
    • , John L. Hopper
    • , Richard Houlston
    • , Peter J. Hulick
    • , David J. Hunter
    • , David G. Huntsman
    • , Gregory Idos
    • , Evgeny N. Imyanitov
    • , Sue Ann Ingles
    • , Claudine Isaacs
    • , Anna Jakubowska
    • , Paul James
    • , Mark A. Jenkins
    • , Mattias Johansson
    • , Mikael Johansson
    • , Esther M. John
    • , Amit D. Joshi
    • , Radka Kaneva
    • , Beth Y. Karlan
    • , Linda E. Kelemen
    • , Tabea Kühl
    • , Kay-Tee Khaw
    • , Elza Khusnutdinova
    • , Adam S. Kibel
    • , Lambertus A. Kiemeney
    • , Jeri Kim
    • , Susanne K. Kjaer
    • , Julia A. Knight
    • , Manolis Kogevinas
    • , Zsofia Kote-Jarai
    • , Stella Koutros
    • , Vessela N. Kristensen
    • , Jolanta Kupryjanczyk
    • , Martin Lacko
    • , Stephan Lam
    • , Diether Lambrechts
    • , Maria Teresa Landi
    • , Philip Lazarus
    • , Nhu D. Le
    • , Eunjung Lee
    • , Flavio Lejbkowicz
    • , Heinz-Josef Lenz
    • , Goska Leslie
    • , Davor Lessel
    • , Jenny Lester
    • , Douglas A. Levine
    • , Li Li
    • , Christopher I. Li
    • , Annika Lindblom
    • , Noralane M. Lindor
    • , Geoffrey Liu
    • , Fotios Loupakis
    • , Jan Lubiński
    • , Lovise Maehle
    • , Christiane Maier
    • , Arto Mannermaa
    • , Loic Le Marchand
    • , Sara Margolin
    • , Taymaa May
    • , Lesley McGuffog
    • , Alfons Meindl
    • , Pooja Middha
    • , Austin Miller
    • , Roger L. Milne
    • , Robert J. MacInnis
    • , Francesmary Modugno
    • , Marco Montagna
    • , Victor Moreno
    • , Kirsten B. Moysich
    • , Lorelei Mucci
    • , Kenneth Muir
    • , Anna Marie Mulligan
    • , Katherine L. Nathanson
    • , David E. Neal
    • , Andrew R. Ness
    • , Susan L. Neuhausen
    • , Heli Nevanlinna
    • , Polly A. Newcomb
    • , Lisa F. Newcomb
    • , Finn Cilius Nielsen
    • , Liene Nikitina-Zake
    • , Børge G. Nordestgaard
    • , Robert L. Nussbaum
    • , Kenneth Offit
    • , Edith Olah
    • , Ali Amin Al Olama
    • , Olufunmilayo I. Olopade
    • , Andrew F. Olshan
    • , Håkan Olsson
    • , Ana Osorio
    • , Hardev Pandha
    • , Jong Y. Park
    • , Nora Pashayan
    • , Michael T. Parsons
    • , Tanja Pejovic
    • , Kathryn L. Penney
    • , Wilbert H M. Peters
    • , Catherine M. Phelan
    • , Amanda I. Phipps
    • , Dijana Plaseska-Karanfilska
    • , Miranda Pring
    • , Darya Prokofyeva
    • , Paolo Radice
    • , Kari Stefansson
    • , Susan J. Ramus
    • , Leon Raskin
    • , Gad Rennert
    • , Hedy S. Rennert
    • , Elizabeth J. van Rensburg
    • , Marjorie J. Riggan
    • , Harvey A. Risch
    • , Angela Risch
    • , Monique J. Roobol
    • , Barry S. Rosenstein
    • , Mary Anne Rossing
    • , Kim De Ruyck
    • , Emmanouil Saloustros
    • , Dale P. Sandler
    • , Elinor J. Sawyer
    • , Matthew B. Schabath
    • , Johanna Schleutker
    • , Marjanka K. Schmidt
    • , V. Wendy Setiawan
    • , Hongbing Shen
    • , Erin M. Siegel
    • , Weiva Sieh
    • , Christian F. Singer
    • , Martha L. Slattery
    • , Karina Dalsgaard Sorensen
    • , Melissa C. Southey
    • , Amanda B. Spurdle
    • , Janet L. Stanford
    • , Victoria L. Stevens
    • , Sebastian Stintzing
    • , Jennifer Stone
    • , Karin Sundfeldt
    • , Rebecca Sutphen
    • , Anthony J. Swerdlow
    • , Eloiza H. Tajara
    • , Catherine M. Tangen
    • , Adonina Tardon
    • , Jack A. Taylor
    • , M. Dawn Teare
    • , Manuel R. Teixeira
    • , Mary Beth Terry
    • , Kathryn L. Terry
    • , Stephen N. Thibodeau
    • , Mads Thomassen
    • , Line Bjørge
    • , Marc Tischkowitz
    • , Amanda E. Toland
    • , Diana Torres
    • , Paul A. Townsend
    • , Ruth C. Travis
    • , Nadine Tung
    • , Shelley S. Tworoger
    • , Cornelia M. Ulrich
    • , Nawaid Usmani
    • , Celine M. Vachon
    • , Els Van Nieuwenhuysen
    • , Ana Vega
    • , Miguel Elías Aguado-Barrera
    • , Qin Wang
    • , Penelope M. Webb
    • , Clarice R. Weinberg
    • , Stephanie Weinstein
    • , Mark C. Weissler
    • , Jeffrey N. Weitzel
    • , Catharine M. L. West
    • , Emily White
    • , Alice S. Whittemore
    • , H-Erich Wichmann
    • , Fredrik Wiklund
    • , Robert Winqvist
    • , Alicja Wolk
    • , Penella Woll
    • , Michael Woods
    • , Anna H. Wu
    • , Xifeng Wu
    • , Drakoulis Yannoukakos
    • , Wei Zheng
    • , Shanbeh Zienolddiny
    • , Argyrios Ziogas
    • , Kristin K. Zorn
    • , Jacqueline M. Lane
    • , Richa Saxena
    • , Duncan Thomas
    • , Rayjean J. Hung
    • , Brenda Diergaarde
    • , James McKay
    • , Ulrike Peters
    • , Li Hsu
    • , Montserrat García-Closas
    • , Rosalind A. Eeles
    • , Georgia Chenevix-Trench
    • , Paul J. Brennan
    • , Christopher A. Haiman
    • , Jacques Simard
    • , Douglas F. Easton
    • , Stephen B. Gruber
    • , Paul D. P. Pharoah
    • , Alkes L. Price
    • , Bogdan Pasaniuc
    • , Christopher I. Amos
    • , Peter Kraft
    •  & Sara Lindström
  • Article | | open

    ER stress and UPR are implicated in various cancers. Here, the authors show that one of the canonical UPR pathways, IRE1α-XBP1 regulates c-MYC signaling to promote prostate tumorigenesis, and pharmacological inhibition of IRE1α with MKC8866 inhibits prostate cancer growth and synergizes with clinically used prostate cancer drugs.

    • Xia Sheng
    • , Hatice Zeynep Nenseth
    • , Su Qu
    • , Omer F. Kuzu
    • , Turid Frahnow
    • , Lukas Simon
    • , Stephanie Greene
    • , Qingping Zeng
    • , Ladan Fazli
    • , Paul S. Rennie
    • , Ian G. Mills
    • , Håvard Danielsen
    • , Fabian Theis
    • , John B. Patterson
    • , Yang Jin
    •  & Fahri Saatcioglu
  • Article | | open

    The connection between DNA replication timing and changes that occur to the epigenome in cancer are still poorly understood. Here, the authors perform Repli-Seq and integrated epigenome analyses and find that genomic regions that undergo long-range epigenetic deregulation in prostate cancer also show concordant differences in replication timing.

    • Qian Du
    • , Saul A. Bert
    • , Nicola J. Armstrong
    • , C. Elizabeth Caldon
    • , Jenny Z. Song
    • , Shalima S. Nair
    • , Cathryn M. Gould
    • , Phuc-Loi Luu
    • , Timothy Peters
    • , Amanda Khoury
    • , Wenjia Qu
    • , Elena Zotenko
    • , Clare Stirzaker
    •  & Susan J. Clark
  • Article | | open

    Focal amplifications are prevalent in many cancer genomes. Here, the authors present AmpliconArchitect (AA), a computational tool for reconstructing their architecture, and reveal an extrachromosomal origin for focal amplifications, including hybrid human-virus elements in HPV-mediated cancers.

    • Viraj Deshpande
    • , Jens Luebeck
    • , Nam-Phuong D. Nguyen
    • , Mehrdad Bakhtiari
    • , Kristen M. Turner
    • , Richard Schwab
    • , Hannah Carter
    • , Paul S. Mischel
    •  & Vineet Bafna
  • Article | | open

    It is difficult to identify cancer driver genes in cancers, for instance BRCA1 mutated breast cancer, that are characterised by large scale genomic alterations. Here, the authors develop genetically engineered mouse models of BRCA1-deficient breast cancer that allow highthroughput in vivo perturbation of candidate driver genes, validating drivers Myc, Met, Pten and Rb1, and identifying MCL1 as a collaborating driver whose targeting can impact efficacy of PARP inhibition.

    • Stefano Annunziato
    • , Julian R. de Ruiter
    • , Linda Henneman
    • , Chiara S. Brambillasca
    • , Catrin Lutz
    • , François Vaillant
    • , Federica Ferrante
    • , Anne Paulien Drenth
    • , Eline van der Burg
    • , Bjørn Siteur
    • , Bas van Gerwen
    • , Roebi de Bruijn
    • , Martine H. van Miltenburg
    • , Ivo J. Huijbers
    • , Marieke van de Ven
    • , Jane E. Visvader
    • , Geoffrey J. Lindeman
    • , Lodewyk F. A. Wessels
    •  & Jos Jonkers
  • Article | | open

    Obesity is linked to increased cancer risk but the impact of body size versus weight distribution in determining the increased risk is unclear. Here the authors examined body mass index, waist circumference, and waist to hip ratio in relation to all-cancer incidence and incidence of seven individual cancers in a population of approximately 26,000 individual and conclude that central adiposity appears to be a stronger predictor of all-cancer risk than body size.

    • Amanda M. Barberio
    • , Asalah Alareeki
    • , Benjamin Viner
    • , Joy Pader
    • , Jennifer E. Vena
    • , Paul Arora
    • , Christine M. Friedenreich
    •  & Darren R. Brenner
  • Article | | open

    Somatic alterations in the exonuclease domain of DNA polymerase ɛ have been linked to the development of highly mutated cancers. Here, the authors report that a major consequence of the most common cancer-associated Polɛ variant is a dramatically increased DNA polymerase activity.

    • Xuanxuan Xing
    • , Daniel P. Kane
    • , Chelsea R. Bulock
    • , Elizabeth A. Moore
    • , Sushma Sharma
    • , Andrei Chabes
    •  & Polina V. Shcherbakova
  • Article | | open

    Enhanced Wnt receptor activity is a major cause of cancer development. Here the authors identify camelid single-domain antibody fragments (VHHs) that bind to the Wnt receptor LRP5/6 ectodomain, determine the crystal structures and show that these VHHs selectively inhibit Wnt3- mediated cellular responses and block the growth of mutant Wnt-hypersensitive intestinal tumor organoids.

    • Nicola Fenderico
    • , Revina C. van Scherpenzeel
    • , Michael Goldflam
    • , Davide Proverbio
    • , Ingrid Jordens
    • , Tomica Kralj
    • , Sarah Stryeck
    • , Tarek Z. Bass
    • , Guy Hermans
    • , Christopher Ullman
    • , Teodor Aastrup
    • , Piet Gros
    •  & Madelon M. Maurice
  • Article | | open

    Acinic cell carcinoma (AciCC) is a rare salivary gland carcinoma that is poorly understood. Here the authors perform genomic, transcriptomic and epigenomic profiling of AciCC and find highly recurrent and specific rearrangements [t(4;9)(q13;q31)], which lead to enhancer hijacking that activates oncogenic transcription factor NR4A3.

    • Florian Haller
    • , Matthias Bieg
    • , Rainer Will
    • , Cindy Körner
    • , Dieter Weichenhan
    • , Alexander Bott
    • , Naveed Ishaque
    • , Pavlo Lutsik
    • , Evgeny A. Moskalev
    • , Sarina K. Mueller
    • , Marion Bähr
    • , Angelika Woerner
    • , Birgit Kaiser
    • , Claudia Scherl
    • , Marlen Haderlein
    • , Kortine Kleinheinz
    • , Rainer Fietkau
    • , Heinrich Iro
    • , Roland Eils
    • , Arndt Hartmann
    • , Christoph Plass
    • , Stefan Wiemann
    •  & Abbas Agaimy
  • Article | | open

    Mucosal melanoma is a rare melanoma subtype that is poorly characterised. Here, the authors sequenced human, canine, and equine melanoma samples and performed a cross-species analysis, which revealed candidate driver genes, recurrent copy number alterations in regions syntenic between species, extensive intra-tumour heterogeneity and potential germline predisposing alleles

    • Kim Wong
    • , Louise van der Weyden
    • , Courtney R. Schott
    • , Alastair Foote
    • , Fernando Constantino-Casas
    • , Sionagh Smith
    • , Jane M. Dobson
    • , Elizabeth P. Murchison
    • , Hong Wu
    • , Iwei Yeh
    • , Douglas R. Fullen
    • , Nancy Joseph
    • , Boris C. Bastian
    • , Rajiv M. Patel
    • , Inigo Martincorena
    • , Carla Daniela Robles-Espinoza
    • , Vivek Iyer
    • , Marieke L. Kuijjer
    • , Mark J. Arends
    • , Thomas Brenn
    • , Paul W. Harms
    • , Geoffrey A. Wood
    •  & David J. Adams
  • Article | | open

    Myelodyplastic hematopoietic stem cells (MDS HSC) have eluded in vivo modeling. Here the authors present a highly efficient MDS patient-derived xenotransplantation model in cytokine-humanized mice with replication of the donors’ genetic complexity and myeloid, erythroid, and megakaryocytic lineage dysplasia.

    • Yuanbin Song
    • , Anthony Rongvaux
    • , Ashley Taylor
    • , Tingting Jiang
    • , Toma Tebaldi
    • , Kunthavai Balasubramanian
    • , Arun Bagale
    • , Yunus Kasim Terzi
    • , Rana Gbyli
    • , Xiaman Wang
    • , Xiaoying Fu
    • , Yimeng Gao
    • , Jun Zhao
    • , Nikolai Podoltsev
    • , Mina Xu
    • , Natalia Neparidze
    • , Ellice Wong
    • , Richard Torres
    • , Emanuela M. Bruscia
    • , Yuval Kluger
    • , Markus G. Manz
    • , Richard A. Flavell
    •  & Stephanie Halene
  • Article | | open

    There are distinct hypermethylation patterns in gene promoters in hepatocellular carcinomas (HCCs). Here, the authors show that the enhancer of C/EBPβ is recurrently hypomethylated in human HCCs, recapitulating this in a transgenic murine model and linking aberrant enhancer hypomethylation to hepatocarcinogenesis.

    • Lei Xiong
    • , Feng Wu
    • , Qiong Wu
    • , Liangliang Xu
    • , Otto K. Cheung
    • , Wei Kang
    • , Myth T. Mok
    • , Lemuel L. M. Szeto
    • , Cheuk-Yin Lun
    • , Raymond W. Lung
    • , Jinglin Zhang
    • , Ken H. Yu
    • , Sau-Dan Lee
    • , Guangcun Huang
    • , Chiou-Miin Wang
    • , Joseph Liu
    • , Zhuo Yu
    • , Dae-Yeul Yu
    • , Jian-Liang Chou
    • , Wan-Hong Huang
    • , Bo Feng
    • , Yue-Sun Cheung
    • , Paul B. Lai
    • , Patrick Tan
    • , Nathalie Wong
    • , Michael W. Chan
    • , Tim H. Huang
    • , Kevin Y. Yip
    • , Alfred S. Cheng
    •  & Ka-Fai To
  • Article | | open

    Medulloblastoma is one of the most prevalent malignant brain tumors in children and has very poor prognosis. In this study, the authors show, using a mouse model of medulloblastoma, that Gfi1 promotes tumor growth by recruiting Lsd1, that this interaction inhibits genes involved in neuronal differentiation, and that Lsd1 may be a therapeutic target in Gfi1-activated tumors.

    • Catherine Lee
    • , Vasilisa A. Rudneva
    • , Serap Erkek
    • , Marc Zapatka
    • , Lianne Q. Chau
    • , Silvia K. Tacheva-Grigorova
    • , Alexandra Garancher
    • , Jessica M. Rusert
    • , Ozlem Aksoy
    • , Robin Lea
    • , Helai P. Mohammad
    • , Jianxun Wang
    • , William A. Weiss
    • , H. Leighton Grimes
    • , Stefan M. Pfister
    • , Paul A. Northcott
    •  & Robert J. Wechsler-Reya
  • Article | | open

    miR-205 is known to have context-dependent tumor suppressive or oncogenic roles. Here, the authors report the host gene of miR-205, MIR205HG as a nuclear lincRNA that maintains the basal identity of prostate cell and prevents luminal cell differentiation via the repression of interferon responsive genes.

    • Valentina Profumo
    • , Barbara Forte
    • , Stefano Percio
    • , Federica Rotundo
    • , Valentina Doldi
    • , Elena Ferrari
    • , Nicola Fenderico
    • , Matteo Dugo
    • , Dario Romagnoli
    • , Matteo Benelli
    • , Riccardo Valdagni
    • , Diletta Dolfini
    • , Nadia Zaffaroni
    •  & Paolo Gandellini
  • Article | | open

    The systemic understanding of oncogenic kinase signalling is still limited. Here, the authors combine chemical proteomics with functional screens to assess the impact of oncogenic Src on the expressed kinome and identify SGK1 as a critical mediator of Src-induced cell transformation.

    • Xiuquan Ma
    • , Luxi Zhang
    • , Jiangning Song
    • , Elizabeth Nguyen
    • , Rachel S. Lee
    • , Samuel J. Rodgers
    • , Fuyi Li
    • , Cheng Huang
    • , Ralf B. Schittenhelm
    • , Howard Chan
    • , Chanly Chheang
    • , Jianmin Wu
    • , Kristin K. Brown
    • , Christina A. Mitchell
    • , Kaylene J. Simpson
    •  & Roger J. Daly
  • Article | | open

    Neuroendocrine prostate cancer (NEPC) is characterized by loss of androgen receptor (AR) signaling during neuroendocrine transdifferentiation, resulting in resistance to AR-targeted therapy. Here they report ONECUT2 to drive NEPC tumorigenesis via regulation of hypoxia signaling and tumor hypoxia, and find hypoxia directed therapy to be effective in NEPC.

    • Haiyang Guo
    • , Xinpei Ci
    • , Musaddeque Ahmed
    • , Junjie Tony Hua
    • , Fraser Soares
    • , Dong Lin
    • , Loredana Puca
    • , Aram Vosoughi
    • , Hui Xue
    • , Estelle Li
    • , Peiran Su
    • , Sujun Chen
    • , Tran Nguyen
    • , Yi Liang
    • , Yuzhe Zhang
    • , Xin Xu
    • , Jing Xu
    • , Anjali V. Sheahan
    • , Wail Ba-Alawi
    • , Si Zhang
    • , Osman Mahamud
    • , Ravi N. Vellanki
    • , Martin Gleave
    • , Robert G. Bristow
    • , Benjamin Haibe-Kains
    • , John T. Poirier
    • , Charles M. Rudin
    • , Ming-Sound Tsao
    • , Bradly G. Wouters
    • , Ladan Fazli
    • , Felix Y. Feng
    • , Leigh Ellis
    • , Theo van der Kwast
    • , Alejandro Berlin
    • , Marianne Koritzinsky
    • , Paul C. Boutros
    • , Amina Zoubeidi
    • , Himisha Beltran
    • , Yuzhuo Wang
    •  & Housheng Hansen He
  • Article | | open

    Overexpression of RAS proteins is frequently observed in patients with hepatocellular carcinoma. Here, the authors identify an HRAS binding protein, the E3 ubiquitin ligase WDR76, which promotes HRAS degradation, thus functioning as a tumour suppressor in liver cancer

    • Woo-Jeong Jeong
    • , Jong-Chan Park
    • , Woo-Shin Kim
    • , Eun Ji Ro
    • , Soung Hoo Jeon
    • , Sang-Kyu Lee
    • , Young Nyun Park
    • , Do Sik Min
    •  & Kang-Yell Choi
  • Article | | open

    The humoral immune response role in cancer is unclear. Here the authors perform an in-depth proteomic profiling of immunoglobulin-bound proteins in plasma from pancreatic ductal adenocarcinoma patients and find cancer-cell specific antibodies neutralized by binding to cancer-cell derived exosomes.

    • Michela Capello
    • , Jody V. Vykoukal
    • , Hiroyuki Katayama
    • , Leonidas E. Bantis
    • , Hong Wang
    • , Deepali L. Kundnani
    • , Clemente Aguilar-Bonavides
    • , Mitzi Aguilar
    • , Satyendra C. Tripathi
    • , Dilsher S. Dhillon
    • , Amin A. Momin
    • , Haley Peters
    • , Matthew H. Katz
    • , Hector Alvarez
    • , Vincent Bernard
    • , Sammy Ferri-Borgogno
    • , Randall Brand
    • , Douglas G. Adler
    • , Matthew A. Firpo
    • , Sean J. Mulvihill
    • , Jeffrey J. Molldrem
    • , Ziding Feng
    • , Ayumu Taguchi
    • , Anirban Maitra
    •  & Samir M. Hanash
  • Article | | open

    Enzymatic reactions caused by neutrophils can cause the elevation of reactive oxygen species (ROS) in tumour tissue, Here, the authors, inspired by the neutrophils, design and test a synthetic cascade reaction which turns ROS into singlet oxygen and demonstrate the application of the designed nanoparticle

    • Qing Wu
    • , Zhigang He
    • , Xia Wang
    • , Qi Zhang
    • , Qingcong Wei
    • , Sunqiang Ma
    • , Cheng Ma
    • , Jiyu Li
    •  & Qigang Wang
  • Article | | open

    Resistance to the new generation EGFR-TKI, Osimertinib, can emerge in patients with EGFR-mutated lung cancer. Here, the authors show that AXL, which is activated by osimertinib, can promote the emergence of tolerant lung cancer cell thus conferring resistance to osimertinib and propose the combination of Osimertinib with AXL inhibitor as a potential therapeutic approach in such resistant cancers.

    • Hirokazu Taniguchi
    • , Tadaaki Yamada
    • , Rong Wang
    • , Keiko Tanimura
    • , Yuta Adachi
    • , Akihiro Nishiyama
    • , Azusa Tanimoto
    • , Shinji Takeuchi
    • , Luiz H. Araujo
    • , Mariana Boroni
    • , Akihiro Yoshimura
    • , Shinsuke Shiotsu
    • , Isao Matsumoto
    • , Satoshi Watanabe
    • , Toshiaki Kikuchi
    • , Satoru Miura
    • , Hiroshi Tanaka
    • , Takeshi Kitazaki
    • , Hiroyuki Yamaguchi
    • , Hiroshi Mukae
    • , Junji Uchino
    • , Hisanori Uehara
    • , Koichi Takayama
    •  & Seiji Yano
  • Article | | open

    Activation of the PPARγ/RXRα pathway in luminal bladder cancers has mainly been linked to PPARG gene amplifications and activating point mutations in RXRα. Here, the authors identify recurrent PPARγ mutations with similar effects and elucidate the structural basis for this mutational PPARγ activation.

    • Natacha Rochel
    • , Clémentine Krucker
    • , Laure Coutos-Thévenot
    • , Judit Osz
    • , Ruiyun Zhang
    • , Elodie Guyon
    • , Wayne Zita
    • , Séverin Vanthong
    • , Oscar Alba Hernandez
    • , Maxime Bourguet
    • , Kays Al Badawy
    • , Florent Dufour
    • , Carole Peluso-Iltis
    • , Syrine Heckler-Beji
    • , Annick Dejaegere
    • , Aurélie Kamoun
    • , Aurélien de Reyniès
    • , Yann Neuzillet
    • , Sandra Rebouissou
    • , Claire Béraud
    • , Hervé Lang
    • , Thierry Massfelder
    • , Yves Allory
    • , Sarah Cianférani
    • , Roland H. Stote
    • , François Radvanyi
    •  & Isabelle Bernard-Pierrot
  • Article | | open

    FLT3 is commonly mutated in acute myeloid leukaemia and treatment with FLT3 inhibitors often ends with relapse. Here, the authors perform exome sequencing of samples from patients treated with the FLT3 inhibitor, crenolanib, to show that resistance occurs due to diverse molecular mechanisms, not primarily due to secondary FLT3 mutations.

    • Haijiao Zhang
    • , Samantha Savage
    • , Anna Reister Schultz
    • , Daniel Bottomly
    • , Libbey White
    • , Erik Segerdell
    • , Beth Wilmot
    • , Shannon K. McWeeney
    • , Christopher A. Eide
    • , Tamilla Nechiporuk
    • , Amy Carlos
    • , Rachel Henson
    • , Chenwei Lin
    • , Robert Searles
    • , Hoang Ho
    • , Yee Ling Lam
    • , Richard Sweat
    • , Courtney Follit
    • , Vinay Jain
    • , Evan Lind
    • , Gautam Borthakur
    • , Guillermo Garcia-Manero
    • , Farhad Ravandi
    • , Hagop M. Kantarjian
    • , Jorge Cortes
    • , Robert Collins
    • , Daelynn R. Buelow
    • , Sharyn D. Baker
    • , Brian J. Druker
    •  & Jeffrey W. Tyner
  • Article | | open

    Chronic hepatitis B virus (HBV) infection is a risk factor for hepatocellular carcinoma (HCC) and is associated with immune tolerance to HBV. Here the authors show, in a transgenic mouse model, that rescuing T cells function via inhibition of co-inhibitory receptor TIGIT results in HCC development via supporting inflammation.

    • Lu Zong
    • , Hui Peng
    • , Cheng Sun
    • , Fenglei Li
    • , Meijuan Zheng
    • , Yongyan Chen
    • , Haiming Wei
    • , Rui Sun
    •  & Zhigang Tian
  • Article | | open

    Deregulation of the RAS GTPase cycle due to mutations in RAS genes is commonly associated with cancer development. Here authors use NMR and mass spectrometry to shows that KRAS phosphorylation via Src alters the conformation of switch I and II regions and thereby impacts the GTPase cycle.

    • Yoshihito Kano
    • , Teklab Gebregiworgis
    • , Christopher B. Marshall
    • , Nikolina Radulovich
    • , Betty P. K. Poon
    • , Jonathan St-Germain
    • , Jonathan D. Cook
    • , Ivette Valencia-Sama
    • , Benjamin M. M. Grant
    • , Silvia Gabriela Herrera
    • , Jinmin Miao
    • , Brian Raught
    • , Meredith S. Irwin
    • , Jeffrey E. Lee
    • , Jen Jen Yeh
    • , Zhong-Yin Zhang
    • , Ming-Sound Tsao
    • , Mitsuhiko Ikura
    •  & Michael Ohh
  • Article | | open

    Glutamine metabolism is increased in proliferating cells under hypoxia potentially generating exceeding nitrogen. Here the authors show that under hypoxia a specific metabolic pathway is activated to push glutamine carbons and excess nitrogen via the reductive pathway to dihyroorotate which is then secreted by the cells and that such pathway is necessary for tumor growth.

    • Yuanyuan Wang
    • , Changsen Bai
    • , Yuxia Ruan
    • , Miao Liu
    • , Qiaoyun Chu
    • , Li Qiu
    • , Chuanzhen Yang
    •  & Binghui Li
  • Article | | open

    Cancer patients are at an increased risk of suicide: elderly, white, unmarried males with localized disease are at highest risk vs other cancer patients. Among those diagnosed at < 50 years of age, the plurality of suicides is from hematologic and testicular tumors; if > 50, from prostate, lung, and colorectal cancer patients.

    • Nicholas G. Zaorsky
    • , Ying Zhang
    • , Leonard Tuanquin
    • , Shirley M. Bluethmann
    • , Henry S. Park
    •  & Vernon M. Chinchilli
  • Article | | open

    Splicing factors are often mutated in hematological malignancies. Here, the authors perform an in vivo shRNA screen in a CEBPA mutant AML mouse model and identify that RBM25 controls the splicing of pre-mRNAs encoding BCL-X and BIN1 to exert its tumour suppressor activities in AML.

    • Ying Ge
    • , Mikkel Bruhn Schuster
    • , Sachin Pundhir
    • , Nicolas Rapin
    • , Frederik Otzen Bagger
    • , Nikos Sidiropoulos
    • , Nadia Hashem
    •  & Bo Torben Porse
  • Article | | open

    Targeting the immune-stimulatory receptor 4-1BB has only yielded modest benefit in cancer treatment. In this study, the authors show that CD73 expression on effector T cells sustained by TGF-β drives tumor resistance to anti-4-1BB therapy and therefore TGF- β blockade can be used to overcome such resistance.

    • Siqi Chen
    • , Jie Fan
    • , Minghui Zhang
    • , Lei Qin
    • , Donye Dominguez
    • , Alan Long
    • , Gaoxiang Wang
    • , Renqiang Ma
    • , Huabin Li
    • , Yi Zhang
    • , Deyu Fang
    • , Jeffrey Sosman
    •  & Bin Zhang