Cancer

  • Article
    | Open Access

    Argonaute 2 (AGO2) binds RAS and is required for cellular transformation. Here, the authors establish a KRAS-driven mouse model of pancreatic cancer with conditional loss of AGO2 and show that the early phase of neoplastic lesion initiation is dependent on EGFR/RAS but not AGO2, while AGO2 is required for pancreatic ductal adenocarcinoma progression and metastasis.

    • Sunita Shankar
    • , Jean Ching-Yi Tien
    • , Ronald F. Siebenaler
    • , Seema Chugh
    • , Vijaya L. Dommeti
    • , Sylvia Zelenka-Wang
    • , Xiao-Ming Wang
    • , Ingrid J. Apel
    • , Jessica Waninger
    • , Sanjana Eyunni
    • , Alice Xu
    • , Malay Mody
    • , Andrew Goodrum
    • , Yuping Zhang
    • , John J. Tesmer
    • , Rahul Mannan
    • , Xuhong Cao
    • , Pankaj Vats
    • , Sethuramasundaram Pitchiaya
    • , Stephanie J. Ellison
    • , Jiaqi Shi
    • , Chandan Kumar-Sinha
    • , Howard C. Crawford
    •  & Arul M. Chinnaiyan
  • Article
    | Open Access

    Focal adhesion kinase (FAK) is required for tumour angiogenesis and growth. Here, the authors show that deletion of pericyte FAK upregulates Gas6-Axl mediated Cyr61 production, which increases endothelial cell proliferation and angiogenesis, while elevating tissue factor production to enhance tumour cell proliferation.

    • Tanguy Lechertier
    • , Louise E. Reynolds
    • , Hyojin Kim
    • , Ana Rita Pedrosa
    • , Jesús Gómez-Escudero
    • , José M. Muñoz-Félix
    • , Silvia Batista
    • , Matthew Dukinfield
    • , Fevzi Demircioglu
    • , Ping Pui Wong
    • , Kylie P. Matchett
    • , Neil C. Henderson
    • , Gabriela D’Amico
    • , Maddy Parsons
    • , Catherine Harwood
    • , Pascal Meier
    •  & Kairbaan M. Hodivala-Dilke
  • Article
    | Open Access

    Conventional co-culture systems often lack physiological complexity of the tumor microenvironment. Here, the authors report an organotypic skin melanoma culture and use this model to investigate the tumor induced suppression on dendritic cells.

    • S. Di Blasio
    • , G. F. van Wigcheren
    • , A. Becker
    • , A. van Duffelen
    • , M. Gorris
    • , K. Verrijp
    • , I. Stefanini
    • , G. J. Bakker
    • , M. Bloemendal
    • , A. Halilovic
    • , A. Vasaturo
    • , G. Bakdash
    • , S. V. Hato
    • , J. H. W. de Wilt
    • , J. Schalkwijk
    • , I. J. M. de Vries
    • , J. C. Textor
    • , E. H. van den Bogaard
    • , M. Tazzari
    •  & C. G. Figdor
  • Article
    | Open Access

    Immunopeptidomics allows identifying the cellular repertoire of MHC-bound peptides, but quantifying them remains challenging. Here, the authors present a method to efficiently generate internal peptide MHC standards and calibration curves, facilitating relative and absolute quantitative immunopeptidomics.

    • Lauren E. Stopfer
    • , Joshua M. Mesfin
    • , Brian A. Joughin
    • , Douglas A. Lauffenburger
    •  & Forest M. White
  • Article
    | Open Access

    It is unclear how resident p16-expressing senescent cells affect the propensity of tissues to develop cancer. Here, the authors show that chronic p16 expression in the mouse epidermis causes hyperplasia and dysplasia through Wnt-mediated paracrine stimulation of proliferating keratinocytes, and can contribute to tumour formation.

    • Narmen Azazmeh
    • , Benjamin Assouline
    • , Eitan Winter
    • , Shmuel Ruppo
    • , Yuval Nevo
    • , Alexander Maly
    • , Karen Meir
    • , Agnieszka K. Witkiewicz
    • , Jonathan Cohen
    • , Sophia V. Rizou
    • , Eli Pikarsky
    • , Chen Luxenburg
    • , Vassilis G. Gorgoulis
    •  & Ittai Ben-Porath
  • Article
    | Open Access

    There are more than 20 known melanoma susceptibility genes. Here, using a massively parallel reporter assay, the authors identify risk-associated variants that alter gene transcription, and demonstrate that expression of one such gene, MX2, leads to the promotion of melanoma in a zebrafish model.

    • Jiyeon Choi
    • , Tongwu Zhang
    • , Andrew Vu
    • , Julien Ablain
    • , Matthew M. Makowski
    • , Leandro M. Colli
    • , Mai Xu
    • , Rebecca C. Hennessey
    • , Jinhu Yin
    • , Harriet Rothschild
    • , Cathrin Gräwe
    • , Michael A. Kovacs
    • , Karen M. Funderburk
    • , Myriam Brossard
    • , John Taylor
    • , Bogdan Pasaniuc
    • , Raj Chari
    • , Stephen J. Chanock
    • , Clive J. Hoggart
    • , Florence Demenais
    • , Jennifer H. Barrett
    • , Matthew H. Law
    • , Mark M. Iles
    • , Kai Yu
    • , Michiel Vermeulen
    • , Leonard I. Zon
    •  & Kevin M. Brown
  • Article
    | Open Access

    Castration resistant prostate cancer patients treated with enzalutamide may develop resistance to the drug. Here, the authors report that monoamine oxidase-A expression is increased in these resistant tumors and that the antidepressants phenelzine/clorgyline can reverse such resistance to further suppress tumor growth

    • Keliang Wang
    • , Jie Luo
    • , Shuyuan Yeh
    • , Bosen You
    • , Jialin Meng
    • , Philip Chang
    • , Yuanjie Niu
    • , Gonghui Li
    • , Changxue Lu
    • , Yezi Zhu
    • , Emmanuel S. Antonarakis
    • , Jun Luo
    • , Chi-Ping Huang
    • , Wanhai Xu
    •  & Chawnshang Chang
  • Article
    | Open Access

    ARID1A, which is often mutated in human endometrial cancer, is a component of the SWI/SNF chromatin remodelling complex. Here, the authors show that Arid1a mutations in the mouse endometrium and primary human endometrial epithelial cells cause widespread reprogramming of gene transcription and result in a loss of response to TGFβ.

    • Yohan Suryo Rahmanto
    • , Wenjing Shen
    • , Xu Shi
    • , Xi Chen
    • , Yu Yu
    • , Zheng-Cheng Yu
    • , Tsutomu Miyamoto
    • , Meng-Horng Lee
    • , Vivek Singh
    • , Ryoichi Asaka
    • , Geoffrey Shimberg
    • , Michele I. Vitolo
    • , Stuart S. Martin
    • , Denis Wirtz
    • , Ronny Drapkin
    • , Jianhua Xuan
    • , Tian-Li Wang
    •  & Ie-Ming Shih
  • Article
    | Open Access

    Synthetic biology can be used to create rationally designed living therapeutics. Here the authors engineer E. coli Nissle to target STING activation in antigen presenting cells for the treatment of solid tumors and demonstrate preclinical activity in murine models.

    • Daniel S. Leventhal
    • , Anna Sokolovska
    • , Ning Li
    • , Christopher Plescia
    • , Starsha A. Kolodziej
    • , Carey W. Gallant
    • , Rudy Christmas
    • , Jian-Rong Gao
    • , Michael J. James
    • , Andres Abin-Fuentes
    • , Munira Momin
    • , Christopher Bergeron
    • , Adam Fisher
    • , Paul F. Miller
    • , Kip A. West
    •  & Jose M. Lora
  • Article
    | Open Access

    The ubiquitin-like modifier ISG15 exerts post-translational protein regulation through ISGylation. Here, the authors show that ISGylation is necessary for pancreatic cancer stem cell self-renewal and tumourigenesis by supporting the recycling of non-functional mitochondria.

    • Sonia Alcalá
    • , Patricia Sancho
    • , Paola Martinelli
    • , Diego Navarro
    • , Coral Pedrero
    • , Laura Martín-Hijano
    • , Sandra Valle
    • , Julie Earl
    • , Macarena Rodríguez-Serrano
    • , Laura Ruiz-Cañas
    • , Katerin Rojas
    • , Alfredo Carrato
    • , Laura García-Bermejo
    • , Miguel Ángel Fernández-Moreno
    • , Patrick C. Hermann
    •  & Bruno Sainz Jr
  • Article
    | Open Access

    Defects in homologous recombination (HR) are found in some triple negative breast cancers, suggesting they may be sensitive to PARP inhibitors. In this phase II clinical trial of the PARP inhibitor rucaparib, changes in Ki67 levels did not correlate with markers of HR deficiency but HR deficiency was detected in 69% of tumours, indicating that PARP inhibitors may be a useful treatment.

    • Neha Chopra
    • , Holly Tovey
    • , Alex Pearson
    • , Ros Cutts
    • , Christy Toms
    • , Paula Proszek
    • , Michael Hubank
    • , Mitch Dowsett
    • , Andrew Dodson
    • , Frances Daley
    • , Divya Kriplani
    • , Heidi Gevensleben
    • , Helen Ruth Davies
    • , Andrea Degasperi
    • , Rebecca Roylance
    • , Stephen Chan
    • , Andrew Tutt
    • , Anthony Skene
    • , Abigail Evans
    • , Judith M. Bliss
    • , Serena Nik-Zainal
    •  & Nicholas C. Turner
  • Article
    | Open Access

    Multiple myeloma is characterised by frequent gene fusions. Here, the authors use data from the Multiple Myeloma Research Foundation CoMMpass Study to further investigate fusion genes in this disease and their clinical relevance.

    • Steven M. Foltz
    • , Qingsong Gao
    • , Christopher J. Yoon
    • , Hua Sun
    • , Lijun Yao
    • , Yize Li
    • , Reyka G. Jayasinghe
    • , Song Cao
    • , Justin King
    • , Daniel R. Kohnen
    • , Mark A. Fiala
    • , Li Ding
    •  & Ravi Vij
  • Article
    | Open Access

    The relative contribution of fallopian tube (FT) or ovarian surface epithelium (OSE) to high-grade serous ovarian cancer (HG-SOC) development is unclear. Here, the authors establish organoid models from murine oviductal and OSE tissues that allow cancer modeling via CRISPR-Cas9 genome editing, and report a dual origin of murine HG-SOC.

    • Kadi Lõhmussaar
    • , Oded Kopper
    • , Jeroen Korving
    • , Harry Begthel
    • , Celien P. H. Vreuls
    • , Johan H. van Es
    •  & Hans Clevers
  • Article
    | Open Access

    Acquired resistance limits the efficacy of PARP inhibitors (PARPi) in high grade serous ovarian cancer (HGSOC). Here, the authors show that inhibition of RNA polymerase I transcription using CX-5461 increases the therapeutic efficacy of PARPi and overcomes PARPi resistance in PDX models of HGSOC.

    • Elaine Sanij
    • , Katherine M. Hannan
    • , Jiachen Xuan
    • , Shunfei Yan
    • , Jessica E. Ahern
    • , Anna S. Trigos
    • , Natalie Brajanovski
    • , Jinbae Son
    • , Keefe T. Chan
    • , Olga Kondrashova
    • , Elizabeth Lieschke
    • , Matthew J. Wakefield
    • , Daniel Frank
    • , Sarah Ellis
    • , Carleen Cullinane
    • , Jian Kang
    • , Gretchen Poortinga
    • , Purba Nag
    • , Andrew J. Deans
    • , Kum Kum Khanna
    • , Linda Mileshkin
    • , Grant A. McArthur
    • , John Soong
    • , Els M. J. J. Berns
    • , Ross D. Hannan
    • , Clare L. Scott
    • , Karen E. Sheppard
    •  & Richard B. Pearson
  • Article
    | Open Access

    Poly-functional helper T cells can have a stronger effect than mono-functional T cells, but whether the response is qualitatively different is not clear. Here the authors show that a population of IL-17+IL-22+, but not single IL-22+, CD4+ T cells are induced by TGF-β, enriched in patients with colorectal cancer (CRC) and drive CRC progression in mice.

    • Laura Garcia Perez
    • , Jan Kempski
    • , Heather M. McGee
    • , Penelope Pelzcar
    • , Theodora Agalioti
    • , Anastasios Giannou
    • , Leonie Konczalla
    • , Leonie Brockmann
    • , Ramez Wahib
    • , Hao Xu
    • , Maria Carolina Amezcua Vesely
    • , Shiwa Soukou
    • , Babett Steglich
    • , Tanja Bedke
    • , Carolin Manthey
    • , Oliver Seiz
    • , Björn-Philipp Diercks
    • , Stylianos Gnafakis
    • , Andreas H. Guse
    • , Daniel Perez
    • , Jakob R. Izbicki
    • , Nicola Gagliani
    • , Richard A. Flavell
    •  & Samuel Huber
  • Article
    | Open Access

    Many germline variants are found in the BRCA2 gene, some of which pre-dispose women to breast and ovarian cancer. Here, the authors develop a method to determine the functional significance of BRCA2 variants and show that it is comparable to the IARC system of classifying variants.

    • Masachika Ikegami
    • , Shinji Kohsaka
    • , Toshihide Ueno
    • , Yukihide Momozawa
    • , Satoshi Inoue
    • , Kenji Tamura
    • , Akihiko Shimomura
    • , Noriko Hosoya
    • , Hiroshi Kobayashi
    • , Sakae Tanaka
    •  & Hiroyuki Mano
  • Article
    | Open Access

    Dysregulation of N6-Methyladenosine (m6A) is associated with cancer progression. Here, authors show that m6A methylation of pyruvate dehydrogenase kinase 4 (PDK4) positively regulates its mRNA stability and translation, and consequently affects glycolysis in cancer cells

    • Zihan Li
    • , Yanxi Peng
    • , Jiexin Li
    • , Zhuojia Chen
    • , Feng Chen
    • , Jian Tu
    • , Shuibin Lin
    •  & Hongsheng Wang
  • Article
    | Open Access

    Recent studies have utilized bulk tumour mRNA sequencing to classify bladder cancers into distinct subgroups. Here, the authors use single cell transcriptomic analysis and cell transplant studies to show that epithelial plasticity can generate basal, luminal and mesenchymal phenotypes in human and murine bladder cancers.

    • John P. Sfakianos
    • , Jorge Daza
    • , Yang Hu
    • , Harry Anastos
    • , Geoffrey Bryant
    • , Rohan Bareja
    • , Ketan K. Badani
    • , Matthew D. Galsky
    • , Olivier Elemento
    • , Bishoy M. Faltas
    •  & David J. Mulholland
  • Article
    | Open Access

    In tumors, hundreds of genes can undergo loss of heterozygosity (LOH). Here, the authors investigate the potential for this LOH as a class of non-driver cancer vulnerabilities.

    • Caitlin A. Nichols
    • , William J. Gibson
    • , Meredith S. Brown
    • , Jack A. Kosmicki
    • , John P. Busanovich
    • , Hope Wei
    • , Laura M. Urbanski
    • , Naomi Curimjee
    • , Ashton C. Berger
    • , Galen F. Gao
    • , Andrew D. Cherniack
    • , Sirano Dhe-Paganon
    • , Brenton R. Paolella
    •  & Rameen Beroukhim
  • Article
    | Open Access

    Androgen receptor (AR) signalling regulates cellular metabolism in prostate cancer. Here, the authors perform a proteomics and metabolomics characterisation of prostate cancer cells adapted to long-term resistance to AR inhibition and show rewiring of glucose and lipid metabolism, and further identify a signature associated with resistance to AR inhibition.

    • Arnaud Blomme
    • , Catriona A. Ford
    • , Ernest Mui
    • , Rachana Patel
    • , Chara Ntala
    • , Lauren E. Jamieson
    • , Mélanie Planque
    • , Grace H. McGregor
    • , Paul Peixoto
    • , Eric Hervouet
    • , Colin Nixon
    • , Mark Salji
    • , Luke Gaughan
    • , Elke Markert
    • , Peter Repiscak
    • , David Sumpton
    • , Giovanny Rodriguez Blanco
    • , Sergio Lilla
    • , Jurre J. Kamphorst
    • , Duncan Graham
    • , Karen Faulds
    • , Gillian M. MacKay
    • , Sarah-Maria Fendt
    • , Sara Zanivan
    •  & Hing Y. Leung
  • Article
    | Open Access

    Cancer stem-like cells are the culprits of tumour recurrence and metastasis, but their regulatory mechanisms are not fully understood. Here, the authors show that the scaffold protein SH3RF3 enhances the stem-like properties of breast cancer by facilitating activation of the JNK-JUN pathway and PTX3 expression.

    • Peiyuan Zhang
    • , Yingjie Liu
    • , Cheng Lian
    • , Xuan Cao
    • , Yuan Wang
    • , Xiaoxun Li
    • , Min Cong
    • , Pu Tian
    • , Xue Zhang
    • , Gang Wei
    • , Tong Liu
    •  & Guohong Hu
  • Article
    | Open Access

    Protein synthesis suppression protects breast cancer cells from clinically relevant stresses like hypoxia. Here, the authors show that unique mRNA isoforms that govern stem cell-like phenotypes escape translational repression to drive tumor progression and chemoresistance.

    • Michael Jewer
    • , Laura Lee
    • , Matthew Leibovitch
    • , Guihua Zhang
    • , Jiahui Liu
    • , Scott D. Findlay
    • , Krista M. Vincent
    • , Kristofferson Tandoc
    • , Dylan Dieters-Castator
    • , Daniela F. Quail
    • , Indrani Dutta
    • , Mackenzie Coatham
    • , Zhihua Xu
    • , Aakshi Puri
    • , Bo-Jhih Guan
    • , Maria Hatzoglou
    • , Andrea Brumwell
    • , James Uniacke
    • , Christos Patsis
    • , Antonis Koromilas
    • , Julia Schueler
    • , Gabrielle M. Siegers
    • , Ivan Topisirovic
    •  & Lynne-Marie Postovit
  • Article
    | Open Access

    Somatic and germline mutations are found at different densities across the genome. Here, the authors compare human somatic tumour mutations with the germline of humans, chimpanzees, and gorillas, and find that the mutation density of tumours correlates better with non-human great apes than with the human germline.

    • José María Heredia-Genestar
    • , Tomàs Marquès-Bonet
    • , David Juan
    •  & Arcadi Navarro
  • Article
    | Open Access

    Many tumors are known to be heterogeneous. Here, the authors examined multiple samples from 84 patients with lung adenocarcinoma and demonstrate that the intratumor heterogeneity of methylation and copy number associates with poor prognosis.

    • Xing Hua
    • , Wei Zhao
    • , Angela C. Pesatori
    • , Dario Consonni
    • , Neil E. Caporaso
    • , Tongwu Zhang
    • , Bin Zhu
    • , Mingyi Wang
    • , Kristine Jones
    • , Belynda Hicks
    • , Lei Song
    • , Joshua Sampson
    • , David C. Wedge
    • , Jianxin Shi
    •  & Maria Teresa Landi
  • Article
    | Open Access

    Nodular lymphocyte-predominant Hodgkin lymphoma with IgD+ lymphocyte-predominant (LP) cells is a rare clinical distinct lymphoma subset of B-cell origin. Here the authors show that antigens expressed by Moraxella catarrhalis are recognized by B cell receptors of IgD+ LP cells, suggesting the contribution of chronic antigen stimulation to lymphomagenesis.

    • Lorenz Thurner
    • , Sylvia Hartmann
    • , Natalie Fadle
    • , Evi Regitz
    • , Maria Kemele
    • , Yoo-Jin Kim
    • , Rainer Maria Bohle
    • , Anna Nimmesgern
    • , Lutz von Müller
    • , Volkhard A. J. Kempf
    • , Marc A. Weniger
    • , Frank Neumann
    • , Nadine Schneider
    • , Martine Vornanen
    • , Christer Sundström
    • , Laurence de Leval
    • , Andreas Engert
    • , Dennis A. Eichenauer
    • , Ralf Küppers
    • , Klaus-Dieter Preuss
    • , Martin-Leo Hansmann
    •  & Michael Pfreundschuh
  • Article
    | Open Access

    Ewing sarcoma is characterized by the fusion of EWSR1 and FLI1. Here, the authors show that EWSR1-FLI1 increases the activity of the developmental transcription factor SOX6, which promotes tumor growth but also increases sensitivity to oxidative stress.

    • Aruna Marchetto
    • , Shunya Ohmura
    • , Martin F. Orth
    • , Maximilian M. L. Knott
    • , Maria V. Colombo
    • , Chiara Arrigoni
    • , Victor Bardinet
    • , David Saucier
    • , Fabienne S. Wehweck
    • , Jing Li
    • , Stefanie Stein
    • , Julia S. Gerke
    • , Michaela C. Baldauf
    • , Julian Musa
    • , Marlene Dallmayer
    • , Laura Romero-Pérez
    • , Tilman L. B. Hölting
    • , James F. Amatruda
    • , Andrea Cossarizza
    • , Anton G. Henssen
    • , Thomas Kirchner
    • , Matteo Moretti
    • , Florencia Cidre-Aranaz
    • , Giuseppina Sannino
    •  & Thomas G. P. Grünewald
  • Article
    | Open Access

    Germline variants that affect the expression or function of protein-coding regions of cancer genes are associated with cancer susceptibility. Here, the authors show that a larger number of germline variants are present in early-onset cancers, while acquired somatic mutations are prevalent in cancers that develop at older age.

    • Tao Qing
    • , Hussein Mohsen
    • , Michal Marczyk
    • , Yixuan Ye
    • , Tess O’Meara
    • , Hongyu Zhao
    • , Jeffrey P. Townsend
    • , Mark Gerstein
    • , Christos Hatzis
    • , Yuval Kluger
    •  & Lajos Pusztai
  • Article
    | Open Access

    Uveal melanoma has a propensity to metastasise. Here, the authors report the whole genome sequence of 103 uveal melanomas and find that the tumour mutational burden is variable and that two subsets of tumours are characterised by MBD4 mutations and a UV exposure signature.

    • Peter A. Johansson
    • , Kelly Brooks
    • , Felicity Newell
    • , Jane M. Palmer
    • , James S. Wilmott
    • , Antonia L. Pritchard
    • , Natasa Broit
    • , Scott Wood
    • , Matteo S. Carlino
    • , Conrad Leonard
    • , Lambros T. Koufariotis
    • , Vaishnavi Nathan
    • , Aaron B. Beasley
    • , Madeleine Howlie
    • , Rebecca Dawson
    • , Helen Rizos
    • , Chris W. Schmidt
    • , Georgina V. Long
    • , Hayley Hamilton
    • , Jens F. Kiilgaard
    • , Timothy Isaacs
    • , Elin S. Gray
    • , Olivia J. Rolfe
    • , John J. Park
    • , Andrew Stark
    • , Graham J. Mann
    • , Richard A. Scolyer
    • , John V. Pearson
    • , Nicolas van Baren
    • , Nicola Waddell
    • , Karin W. Wadt
    • , Lindsay A. McGrath
    • , Sunil K. Warrier
    • , William Glasson
    •  & Nicholas K. Hayward
  • Article
    | Open Access

    The development of chemoresistance is a major hurdle in triple negative breast cancer (TNBC). Here, the authors show that lysyl oxidase (LOX) is overexpressed in chemoresistant TNBCs, and when inhibited reduces collagen cross-linking, fibronectin fibril assembly, and downstream integrin signalling, overcoming resistance.

    • Ozge Saatci
    • , Aysegul Kaymak
    • , Umar Raza
    • , Pelin G. Ersan
    • , Ozge Akbulut
    • , Carolyn E. Banister
    • , Vitali Sikirzhytski
    • , Unal Metin Tokat
    • , Gamze Aykut
    • , Suhail A. Ansari
    • , Hayriye Tatli Dogan
    • , Mehmet Dogan
    • , Pouria Jandaghi
    • , Aynur Isik
    • , Fatma Gundogdu
    • , Kemal Kosemehmetoglu
    • , Omer Dizdar
    • , Sercan Aksoy
    • , Aytekin Akyol
    • , Aysegul Uner
    • , Phillip J. Buckhaults
    • , Yasser Riazalhosseini
    •  & Ozgur Sahin
  • Article
    | Open Access

    Acquired resistance to cancer therapies reflects the ability of cancers to adapt to therapy-imposed selective pressures. Here, the authors elucidate the dynamics of developing resistance to ALK inhibitors in an ALK+ lung cancer cell line showing that resistance originates from drug-specific tolerant cancer cells and it develops as a gradual adaptation.

    • Robert Vander Velde
    • , Nara Yoon
    • , Viktoriya Marusyk
    • , Arda Durmaz
    • , Andrew Dhawan
    • , Daria Miroshnychenko
    • , Diego Lozano-Peral
    • , Bina Desai
    • , Olena Balynska
    • , Jan Poleszhuk
    • , Liu Kenian
    • , Mingxiang Teng
    • , Mohamed Abazeed
    • , Omar Mian
    • , Aik Choon Tan
    • , Eric Haura
    • , Jacob Scott
    •  & Andriy Marusyk
  • Article
    | Open Access

    YAP1 gene fusions are found in subgroups of paediatric ependymomas. Here the authors show that YAP1 activation in NeuroD6 positive neuronal precursor cells can induce ependymoma-like tumours in mice.

    • Noreen Eder
    • , Federico Roncaroli
    • , Marie-Charlotte Dolmart
    • , Stuart Horswell
    • , Felipe Andreiuolo
    • , Helen R. Flynn
    • , Andre T. Lopes
    • , Suzanne Claxton
    • , John-Paul Kilday
    • , Lucy Collinson
    • , Jun-Hao Mao
    • , Torsten Pietsch
    • , Barry Thompson
    • , Ambrosius P. Snijders
    •  & Sila K. Ultanir
  • Article
    | Open Access

    The alternative splicing regulator MBNL1 is overexpressed in MLL-rearranged leukaemia. Here, the authors show that MBNL1-mediated alternative splicing leads to a specific splicing profile in MLL-rearranged leukaemia and loss or inhibition of MBNL1 impairs leukaemia development in vitro and in vivo.

    • Svetlana S. Itskovich
    • , Arun Gurunathan
    • , Jason Clark
    • , Matthew Burwinkel
    • , Mark Wunderlich
    • , Mikaela R. Berger
    • , Aishwarya Kulkarni
    • , Kashish Chetal
    • , Meenakshi Venkatasubramanian
    • , Nathan Salomonis
    • , Ashish R. Kumar
    •  & Lynn H. Lee
  • Article
    | Open Access

    Effective combination therapies to improve the efficacy of BET inhibitors are currently under investigation. Here, the authors examine palbociclib and paclitaxel as two promising candidates for combination therapies with BET inhibition in breast cancer and investigate the dynamics of resistance to these combinations through DNA barcoding and mathematical modelling.

    • Jennifer Y. Ge
    • , Shaokun Shu
    • , Mijung Kwon
    • , Bojana Jovanović
    • , Katherine Murphy
    • , Anushree Gulvady
    • , Anne Fassl
    • , Anne Trinh
    • , Yanan Kuang
    • , Grace A. Heavey
    • , Adrienne Luoma
    • , Cloud Paweletz
    • , Aaron R. Thorner
    • , Kai W. Wucherpfennig
    • , Jun Qi
    • , Myles Brown
    • , Piotr Sicinski
    • , Thomas O. McDonald
    • , David Pellman
    • , Franziska Michor
    •  & Kornelia Polyak
  • Article
    | Open Access

    Fasting diets are emerging as an approach to delay tumor progression and improve cancer therapies. Here, the authors show that the combination of fasting-mimicking diet with vitamin C decreases tumor development and increases chemotherapy efficacy in KRAS-mutant cancer.

    • Maira Di Tano
    • , Franca Raucci
    • , Claudio Vernieri
    • , Irene Caffa
    • , Roberta Buono
    • , Maura Fanti
    • , Sebastian Brandhorst
    • , Giuseppe Curigliano
    • , Alessio Nencioni
    • , Filippo de Braud
    •  & Valter D. Longo
  • Article
    | Open Access

    Detailed understanding of how cancer cells transition from a drug sensitive to a tolerant state is lacking. Here, using single cell proteomic and metabolic data the authors uncover that isogenic BRAF mutant melanoma cells can take two distinct paths to become tolerant to BRAF inhibition.

    • Yapeng Su
    • , Melissa E. Ko
    • , Hanjun Cheng
    • , Ronghui Zhu
    • , Min Xue
    • , Jessica Wang
    • , Jihoon W. Lee
    • , Luke Frankiw
    • , Alexander Xu
    • , Stephanie Wong
    • , Lidia Robert
    • , Kaitlyn Takata
    • , Dan Yuan
    • , Yue Lu
    • , Sui Huang
    • , Antoni Ribas
    • , Raphael Levine
    • , Garry P. Nolan
    • , Wei Wei
    • , Sylvia K. Plevritis
    • , Guideng Li
    • , David Baltimore
    •  & James R. Heath
  • Article
    | Open Access

    In lung cancer, relatively few germline mutations are known to impact risk. Here the authors looked at rare variants in 39,146 individuals and find novel germline mutations associated with risk, as well as implicating ATM and a new candidate gene for lung cancer risk.

    • Xuemei Ji
    • , Semanti Mukherjee
    • , Maria Teresa Landi
    • , Yohan Bosse
    • , Philippe Joubert
    • , Dakai Zhu
    • , Ivan Gorlov
    • , Xiangjun Xiao
    • , Younghun Han
    • , Olga Gorlova
    • , Rayjean J. Hung
    • , Yonathan Brhane
    • , Robert Carreras-Torres
    • , David C. Christiani
    • , Neil Caporaso
    • , Mattias Johansson
    • , Geoffrey Liu
    • , Stig E. Bojesen
    • , Loic Le Marchand
    • , Demetrios Albanes
    • , Heike Bickeböller
    • , Melinda C. Aldrich
    • , William S. Bush
    • , Adonina Tardon
    • , Gad Rennert
    • , Chu Chen
    • , Jinyoung Byun
    • , Konstantin H. Dragnev
    • , John K. Field
    • , Lambertus FA. Kiemeney
    • , Philip Lazarus
    • , Shan Zienolddiny
    • , Stephen Lam
    • , Matthew B. Schabath
    • , Angeline S. Andrew
    • , Pier A. Bertazzi
    • , Angela C. Pesatori
    • , Nancy Diao
    • , Li Su
    • , Lei Song
    • , Ruyang Zhang
    • , Natasha Leighl
    • , Jakob S. Johansen
    • , Anders Mellemgaard
    • , Walid Saliba
    • , Christopher Haiman
    • , Lynne Wilkens
    • , Ana Fernandez-Somoano
    • , Guillermo Fernandez-Tardon
    • , Erik H. F. M. van der Heijden
    • , Jin Hee Kim
    • , Michael P. A. Davies
    • , Michael W. Marcus
    • , Hans Brunnström
    • , Jonas Manjer
    • , Olle Melander
    • , David C. Muller
    • , Kim Overvad
    • , Antonia Trichopoulou
    • , Rosario Tumino
    • , Gary E. Goodman
    • , Angela Cox
    • , Fiona Taylor
    • , Penella Woll
    • , Erich Wichmann
    • , Thomas Muley
    • , Angela Risch
    • , Albert Rosenberger
    • , Kjell Grankvist
    • , Mikael Johansson
    • , Frances Shepherd
    • , Ming-Sound Tsao
    • , Susanne M. Arnold
    • , Eric B. Haura
    • , Ciprian Bolca
    • , Ivana Holcatova
    • , Vladimir Janout
    • , Milica Kontic
    • , Jolanta Lissowska
    • , Anush Mukeria
    • , Simona Ognjanovic
    • , Tadeusz M. Orlowski
    • , Ghislaine Scelo
    • , Beata Swiatkowska
    • , David Zaridze
    • , Per Bakke
    • , Vidar Skaug
    • , Lesley M. Butler
    • , Kenneth Offit
    • , Preethi Srinivasan
    • , Chaitanya Bandlamudi
    • , Matthew D. Hellmann
    • , David B. Solit
    • , Mark E. Robson
    • , Charles M. Rudin
    • , Zsofia K. Stadler
    • , Barry S. Taylor
    • , Michael F. Berger
    • , Richard Houlston
    • , John McLaughlin
    • , Victoria Stevens
    • , David C. Nickle
    • , Ma’en Obeidat
    • , Wim Timens
    • , María Soler Artigas
    • , Sanjay Shete
    • , Hermann Brenner
    • , Stephen Chanock
    • , Paul Brennan
    • , James D. McKay
    •  & Christopher I. Amos
  • Article
    | Open Access

    Recombinant T-cells receptors can redirect naïve T cells but often have low or uneven expression. Here, the authors model mutations in TCR constant domains to increase T cell receptor expression, assembly, and stability and generate bispecific molecules.

    • Karen Froning
    • , Jack Maguire
    • , Arlene Sereno
    • , Flora Huang
    • , Shawn Chang
    • , Kenneth Weichert
    • , Anton J. Frommelt
    • , Jessica Dong
    • , Xiufeng Wu
    • , Heather Austin
    • , Elaine M. Conner
    • , Jonathan R. Fitchett
    • , Aik Roy Heng
    • , Deepa Balasubramaniam
    • , Mark T. Hilgers
    • , Brian Kuhlman
    •  & Stephen J. Demarest
  • Article
    | Open Access

    Understanding the mechanisms that lead to lung adenocarcinoma metastasis is important for identifying new therapeutics. Here, the authors document the changes in the transcriptome of human lung adenocarcinoma using single-cell sequencing and link cancer cell signatures to immune cell dynamics.

    • Nayoung Kim
    • , Hong Kwan Kim
    • , Kyungjong Lee
    • , Yourae Hong
    • , Jong Ho Cho
    • , Jung Won Choi
    • , Jung-Il Lee
    • , Yeon-Lim Suh
    • , Bo Mi Ku
    • , Hye Hyeon Eum
    • , Soyean Choi
    • , Yoon-La Choi
    • , Je-Gun Joung
    • , Woong-Yang Park
    • , Hyun Ae Jung
    • , Jong-Mu Sun
    • , Se-Hoon Lee
    • , Jin Seok Ahn
    • , Keunchil Park
    • , Myung-Ju Ahn
    •  & Hae-Ock Lee
  • Article
    | Open Access

    The molecular mechanisms leading to basal extrusion are unclear. Here, the authors use the Drosophila accessory gland to model human prostate acini and show that Ras/MAPK and PI3K/AKT/mTOR pathways are co-activated in two autocrine loops by dEGF and dIGF, inducing basal extrusion and subsequent tumour formation.

    • Amandine Rambur
    • , Corinne Lours-Calet
    • , Claude Beaudoin
    • , Julio Buñay
    • , Marine Vialat
    • , Vincent Mirouse
    • , Amalia Trousson
    • , Yoan Renaud
    • , Jean-Marc A. Lobaccaro
    • , Silvère Baron
    • , Laurent Morel
    •  & Cyrille de Joussineau
  • Article
    | Open Access

    Constitutive Btk signaling drives several B-cell cancers. Here the authors demonstrate key allosteric intramolecular interactions between the SH2 domain and the kinase domain of Btk, and propose an alternative approach for inhibition of both wild-type and tyrosine kinase inhibitor-resistant Btk.

    • Daniel P. Duarte
    • , Allan J. Lamontanara
    • , Giuseppina La Sala
    • , Sukyo Jeong
    • , Yoo-Kyoung Sohn
    • , Alejandro Panjkovich
    • , Sandrine Georgeon
    • , Tim Kükenshöner
    • , Maria J. Marcaida
    • , Florence Pojer
    • , Marco De Vivo
    • , Dmitri Svergun
    • , Hak-Sung Kim
    • , Matteo Dal Peraro
    •  & Oliver Hantschel
  • Article
    | Open Access

    Imaging Cherenkov emission during radiotherapy can provide information on the delivered radiation dose, but is attenuated by optical properties of the tissue. Here the authors derive a correction factor applicable to breast X-ray radiotherapy in human subjects to improve the correlation between Cherenkov emission intensity and dose.

    • R. L. Hachadorian
    • , P. Bruza
    • , M. Jermyn
    • , D. J. Gladstone
    • , B. W. Pogue
    •  & L. A. Jarvis
  • Article
    | Open Access

    ABCG2 is a human ABC transporter that actively extrudes a wide variety of compounds from cells but the mechanisms of multidrug transport remain obscure. Here authors present cryo-EM structures of ABCG2 in the apo state, and bound to the three structurally distinct chemotherapeutics and demonstrate how these molecules open the closed conformation of the transporter.

    • Benjamin J. Orlando
    •  & Maofu Liao
  • Article
    | Open Access

    The shattering of chromosomes is a dramatic early event in tumourigenesis and is termed chromothripsis. Here, the authors examine chromothripsis across 28 tumour types and show that 49% of cancers exhibit features of chromothripsis.

    • Natalia Voronina
    • , John K. L. Wong
    • , Daniel Hübschmann
    • , Mario Hlevnjak
    • , Sebastian Uhrig
    • , Christoph E. Heilig
    • , Peter Horak
    • , Simon Kreutzfeldt
    • , Andreas Mock
    • , Albrecht Stenzinger
    • , Barbara Hutter
    • , Martina Fröhlich
    • , Benedikt Brors
    • , Arne Jahn
    • , Barbara Klink
    • , Laura Gieldon
    • , Lina Sieverling
    • , Lars Feuerbach
    • , Priya Chudasama
    • , Katja Beck
    • , Matthias Kroiss
    • , Christoph Heining
    • , Lino Möhrmann
    • , Andrea Fischer
    • , Evelin Schröck
    • , Hanno Glimm
    • , Marc Zapatka
    • , Peter Lichter
    • , Stefan Fröhling
    •  & Aurélie Ernst
  • Article
    | Open Access

    One cause of relapse in cancer patients treated with chimeric antigen receptor (CAR) T cells is the loss of CAR-targeted antigens, which is particularly common in multiple myeloma (MM). Here the authors engineer a CAR recognizing two common MM-associated antigens and demonstrate its superiority to single-antigen CARs in a mouse model of MM.

    • Eugenia Zah
    • , Eunwoo Nam
    • , Vinya Bhuvan
    • , Uyen Tran
    • , Brenda Y. Ji
    • , Stanley B. Gosliner
    • , Xiuli Wang
    • , Christine E. Brown
    •  & Yvonne Y. Chen
  • Article
    | Open Access

    p85β (PIK3R2), a regulatory subunit of PI3K, has oncogenic properties. Here the authors show that p85β promotes AXL protein stability, which in turn activates p110 to induce PDK1/SGK3 signaling, and therapeutically, p85β-expressing ovarian cancer cells are sensitive to AXL inhibition.

    • Ling Rao
    • , Victor C. Y. Mak
    • , Yuan Zhou
    • , Dong Zhang
    • , Xinran Li
    • , Chloe C. Y. Fung
    • , Rakesh Sharma
    • , Chao Gu
    • , Yiling Lu
    • , George L. Tipoe
    • , Annie N. Y. Cheung
    • , Gordon B. Mills
    •  & Lydia W. T. Cheung
  • Article
    | Open Access

    Targeted therapies for solid tumors in children, adolescents, and young adults (C-AYA) lag behind that of adult carcinomas. Here, the authors study the germline genomic signatures of 1,507 C-AYA patients with solid tumors and find pathogenic/likely pathogenic germline variants in diverse genes of which 1/3 of these alterations are druggable.

    • Sara Akhavanfard
    • , Roshan Padmanabhan
    • , Lamis Yehia
    • , Feixiong Cheng
    •  & Charis Eng
  • Article
    | Open Access

    Most testicular germ-cell tumours are exquisitely sensitive to platinum-based chemotherapies, but little is known about why 10% are resistant. Here, the authors explore the potential underlying mechanisms by probing the genomic landscape of platinum-resistant disease.

    • Chey Loveday
    • , Kevin Litchfield
    • , Paula Z. Proszek
    • , Alex J. Cornish
    • , Flavia Santo
    • , Max Levy
    • , Geoff Macintyre
    • , Amy Holryod
    • , Peter Broderick
    • , Darshna Dudakia
    • , Barbara Benton
    • , Maise Al Bakir
    • , Crispin Hiley
    • , Emily Grist
    • , Charles Swanton
    • , Robert Huddart
    • , Tom Powles
    • , Simon Chowdhury
    • , Janet Shipley
    • , Simon O’Connor
    • , James D. Brenton
    • , Alison Reid
    • , David Gonzalez de Castro
    • , Richard S. Houlston
    •  & Clare Turnbull