Oncology

  • Article
    | Open Access

    Rap1 is a telomeric protein that is highly expressed in cancers. Here, the authors show that Rap1 interacts with several DNA repair proteins independent of its telomere function to enhance DNA repair and that its deficiency leads to accelerated tumorigenesis, but enhanced sensitivity to genotoxic stress.

    • Ekta Khattar
    • , Kyaw Ze Ya Maung
    • , Chen Li Chew
    • , Arkasubhra Ghosh
    • , Michelle Meng Huang Mok
    • , Pei Lee
    • , Jun Zhang
    • , Wei Hong Jeff Chor
    • , Gökhan Cildir
    • , Chelsia Qiuxia Wang
    • , Nur Khairiah Mohd-Ismail
    • , Desmond Wai Loon Chin
    • , Soo Chin Lee
    • , Henry Yang
    • , Yong-Jae Shin
    • , Do-Hyun Nam
    • , Liming Chen
    • , Alan Prem Kumar
    • , Lih Wen Deng
    • , Masahito Ikawa
    • , Jayantha Gunaratne
    • , Motomi Osato
    •  & Vinay Tergaonkar
  • Article
    | Open Access

    Glioblastoma cells are known to be able to adapt easily to different environments. The authors study the dynamic adaptation of glioblastoma cells to the heterogenous brain tumor microenvironment, showing that tumor cells demonstrate varying plasticity of their transcriptomic profiles and an ability to survive new stimuli, in part, by propagating stochastic perturbations over their gene-regulatory network.

    • Orieta Celiku
    • , Mark R. Gilbert
    •  & Orit Lavi
  • Article
    | Open Access

    The authors report a co-occurrence of the U2AF1 S34F splicing factor mutation and ROS1 translocations in lung adenocarcinomas and profile effects of S34F on transcriptome-wide RNA binding. They further show that U2AF1 S34F enhances invasive potential and alters splicing of ROS1 fusion transcripts

    • Mohammad S. Esfahani
    • , Luke J. Lee
    • , Young-Jun Jeon
    • , Ryan A. Flynn
    • , Henning Stehr
    • , Angela B. Hui
    • , Noriko Ishisoko
    • , Eric Kildebeck
    • , Aaron M. Newman
    • , Scott V. Bratman
    • , Matthew H. Porteus
    • , Howard Y. Chang
    • , Ash A. Alizadeh
    •  & Maximilian Diehn
  • Article
    | Open Access

    Understanding the genomic features of dedifferentiated liposarcoma (DDLPS) is likely to uncover new options for management. Here, the authors reveal three prognostic groups, and highlight molecular markers associated with malignant transformation.

    • Makoto Hirata
    • , Naofumi Asano
    • , Kotoe Katayama
    • , Akihiko Yoshida
    • , Yusuke Tsuda
    • , Masaya Sekimizu
    • , Sachiyo Mitani
    • , Eisuke Kobayashi
    • , Motokiyo Komiyama
    • , Hiroyuki Fujimoto
    • , Takahiro Goto
    • , Yukihide Iwamoto
    • , Norifumi Naka
    • , Shintaro Iwata
    • , Yoshihiro Nishida
    • , Toru Hiruma
    • , Hiroaki Hiraga
    • , Hirotaka Kawano
    • , Toru Motoi
    • , Yoshinao Oda
    • , Daisuke Matsubara
    • , Masashi Fujita
    • , Tatsuhiro Shibata
    • , Hidewaki Nakagawa
    • , Robert Nakayama
    • , Tadashi Kondo
    • , Seiya Imoto
    • , Satoru Miyano
    • , Akira Kawai
    • , Rui Yamaguchi
    • , Hitoshi Ichikawa
    •  & Koichi Matsuda
  • Article
    | Open Access

    BRCA1 mutations located within the BRCT domain result in proteasomal degradation and sensitivity to PARP inhibitors (PARPi). Here, the authors report genetic rearrangements in the BRCA1 gene that generate a BRCT-less BRCA1 protein isoform, which avoids degradation and leads to PARPi resistance.

    • Yifan Wang
    • , Andrea J. Bernhardy
    • , Joseph Nacson
    • , John J. Krais
    • , Yin-Fei Tan
    • , Emmanuelle Nicolas
    • , Marc R. Radke
    • , Elizabeth Handorf
    • , Alba Llop-Guevara
    • , Judith Balmaña
    • , Elizabeth M. Swisher
    • , Violeta Serra
    • , Suraj Peri
    •  & Neil Johnson
  • Article
    | Open Access

    Effective precision medicine strategies rely on the ability to predict tumour behaviour based on molecular characteristics. Here, the authors build models to predict multiple distinct gene expression patterns using DNA copy number alterations

    • Youli Xia
    • , Cheng Fan
    • , Katherine A. Hoadley
    • , Joel S. Parker
    •  & Charles M. Perou
  • Article
    | Open Access

    PARG catalyzes the removal of poly(ADP-ribose) (PAR) from target proteins and executes critical functions in the DNA damage response. Here the authors provide structural and biological insight with small molecule PARG inhibitors and show that PARG inhibition sensitizes cells to ionizing radiation and kills cancer cells through replication fork defects.

    • Jerry H. Houl
    • , Zu Ye
    • , Chris A. Brosey
    • , Lakshitha P. F. Balapiti-Modarage
    • , Sarita Namjoshi
    • , Albino Bacolla
    • , Daniel Laverty
    • , Brian L. Walker
    • , Yasin Pourfarjam
    • , Leslie S. Warden
    • , Naga Babu Chinnam
    • , Davide Moiani
    • , Roderick A. Stegeman
    • , Mei-Kuang Chen
    • , Mien-Chie Hung
    • , Zachary D. Nagel
    • , Tom Ellenberger
    • , In-Kwon Kim
    • , Darin E. Jones
    • , Zamal Ahmed
    •  & John A. Tainer
  • Article
    | Open Access

    Polymorphisms in LMO1 are associated with increased susceptibility to develop neuroblastoma. Here, the authors show that LMO1 directly induces the transcription factor ASCL1, which regulates the differentiation of neurons, demonstrating that ASCL1 is part of the adrenergic neuroblastoma core regulatory circuit.

    • Lu Wang
    • , Tze King Tan
    • , Adam D. Durbin
    • , Mark W. Zimmerman
    • , Brian J. Abraham
    • , Shi Hao Tan
    • , Phuong Cao Thi Ngoc
    • , Nina Weichert-Leahey
    • , Koshi Akahane
    • , Lee N. Lawton
    • , Jo Lynne Rokita
    • , John M. Maris
    • , Richard A. Young
    • , A. Thomas Look
    •  & Takaomi Sanda
  • Article
    | Open Access

    Glycolysis is elevated in many cancers. In this study, the authors show that lactoylglutathione, a by-product of methylglyoxal produced from increased glycolysis, is elevated in lung cancer in mouse models and humans, arguing reactive metabolite production can be a liability for cancers.

    • Alba Luengo
    • , Keene L. Abbott
    • , Shawn M. Davidson
    • , Aaron M. Hosios
    • , Brandon Faubert
    • , Sze Ham Chan
    • , Elizaveta Freinkman
    • , Lauren G. Zacharias
    • , Thomas P. Mathews
    • , Clary B. Clish
    • , Ralph J. DeBerardinis
    • , Caroline A. Lewis
    •  & Matthew G. Vander Heiden
  • Article
    | Open Access

    Intermediate transitions between epithelial and mesenchymal states are associated with tumor progression. Here using mass cytometry, Plevritis and colleagues develop a computational framework to resolve and map these trajectories in lung cancer cells and clinical specimens.

    • Loukia G. Karacosta
    • , Benedict Anchang
    • , Nikolaos Ignatiadis
    • , Samuel C. Kimmey
    • , Jalen A. Benson
    • , Joseph B. Shrager
    • , Robert Tibshirani
    • , Sean C. Bendall
    •  & Sylvia K. Plevritis
  • Article
    | Open Access

    Yamanaka factors can reprogram somatic and cancer cells into induced pluripotent stem cells. Here, the authors show that the induction of these factors in acute myeloid leukemia leads to apoptosis of leukemia cells in vivo, and this is through modulation of chromatin accessibility to apoptotic genes and accompanied by H3K9me3 dysregulation.

    • Yajie Wang
    • , Ting Lu
    • , Guohuan Sun
    • , Yawei Zheng
    • , Shangda Yang
    • , Hongyan Zhang
    • , Sha Hao
    • , Yanfeng Liu
    • , Shihui Ma
    • , Houyu Zhang
    • , Yongxin Ru
    • , Shaorong Gao
    • , Kuangyu Yen
    • , Hui Cheng
    •  & Tao Cheng
  • Article
    | Open Access

    Tobacco use is one of the major risk factors for Head and neck squamous cell carcinoma (HNSCC). Here, the authors report an immune-competent syngeneic mouse model that mimics human tobacco-related HNSCC, and develops tumors in the tongue, and report a high response rate to anti-CTLA-4 therapy.

    • Zhiyong Wang
    • , Victoria H. Wu
    • , Michael M. Allevato
    • , Mara Gilardi
    • , Yudou He
    • , Juan Luis Callejas-Valera
    • , Lynn Vitale-Cross
    • , Daniel Martin
    • , Panomwat Amornphimoltham
    • , James Mcdermott
    • , Bryan S. Yung
    • , Yusuke Goto
    • , Alfredo A. Molinolo
    • , Andrew B. Sharabi
    • , Ezra E. W. Cohen
    • , Qianming Chen
    • , J. Guy Lyons
    • , Ludmil B. Alexandrov
    •  & J. Silvio Gutkind
  • Article
    | Open Access

    Aurora-A kinase is frequently over-expressed in tumours. Here, the authors show that it modulates the activity of lactate dehydrogenase B, resulting in enhanced glycolysis, bio-synthesis and tumour growth.

    • Aoxing Cheng
    • , Peng Zhang
    • , Bo Wang
    • , Dongdong Yang
    • , Xiaotao Duan
    • , Yongliang Jiang
    • , Tian Xu
    • , Ya Jiang
    • , Jiahui Shi
    • , Chengtao Ding
    • , Gao Wu
    • , Zhihong Sang
    • , Qiang Wu
    • , Hua Wang
    • , Mian Wu
    • , Zhiyong Zhang
    • , Xin Pan
    • , Yue-yin Pan
    • , Ping Gao
    • , Huafeng Zhang
    • , Cong-zhao Zhou
    • , Jing Guo
    •  & Zhenye Yang
  • Article
    | Open Access

    Infection or chronic inflammation is a risk factor for childhood B-cell precursor acute lymphoblastic leukemia. Here, the authors show that the DNA editing enzyme AID is expressed in infected B cells but using genetic mouse models show that it does not contribute to leukemia pathogenesis.

    • Guillermo Rodríguez-Hernández
    • , Friederike V. Opitz
    • , Pilar Delgado
    • , Carolin Walter
    • , Ángel F. Álvarez-Prado
    • , Inés González-Herrero
    • , Franziska Auer
    • , Ute Fischer
    • , Stefan Janssen
    • , Christoph Bartenhagen
    • , Javier Raboso-Gallego
    • , Ana Casado-García
    • , Alberto Orfao
    • , Oscar Blanco
    • , Diego Alonso-López
    • , Javier De Las Rivas
    • , Sara González de Tena-Dávila
    • , Markus Müschen
    • , Martin Dugas
    • , Francisco Javier García Criado
    • , María Begoña García Cenador
    • , Carolina Vicente-Dueñas
    • , Julia Hauer
    • , Almudena R. Ramiro
    • , Isidro Sanchez-Garcia
    •  & Arndt Borkhardt
  • Article
    | Open Access

    How a precancerous form (dysplasia) becomes gastric cancer is unclear. Here, the authors assess the role of Kras activation in heterogenous dysplastic cells in murine stomach corpus organoids, identifying two dysplastic stem cell populations and show that MEK inhibition causes alterations in cell behavior.

    • Jimin Min
    • , Paige N. Vega
    • , Amy C. Engevik
    • , Janice A. Williams
    • , Qing Yang
    • , Loraine M. Patterson
    • , Alan J. Simmons
    • , R. Jarrett Bliton
    • , Joshua W. Betts
    • , Ken S. Lau
    • , Scott T. Magness
    • , James R. Goldenring
    •  & Eunyoung Choi
  • Article
    | Open Access

    Sequencing cancer genomes reveals low frequency novel somatic variants without known function. Here, the authors leverage statistical methodology from the fields of computational linguistics and ecology to highlight the potentially important signals harboured by these novel variants that are often dismissed.

    • Saptarshi Chakraborty
    • , Arshi Arora
    • , Colin B. Begg
    •  & Ronglai Shen
  • Article
    | Open Access

    In breast cancer, the immune infiltration of the tumour associates with clinical outcome. Here, the authors infer immune context based on gene expression data and identify a new independent subtype linked to pro-tumorigenic immune infiltration.

    • Xavier Tekpli
    • , Tonje Lien
    • , Andreas Hagen Røssevold
    • , Daniel Nebdal
    • , Elin Borgen
    • , Hege Oma Ohnstad
    • , Jon Amund Kyte
    • , Johan Vallon-Christersson
    • , Marie Fongaard
    • , Eldri Undlien Due
    • , Lisa Gregusson Svartdal
    • , My Anh Tu Sveli
    • , Øystein Garred
    • , Anne-Lise Børresen-Dale
    • , Ellen Schlichting
    • , Torill Sauer
    • , Jürgen Geisler
    • , Solveig Hofvind
    • , Tone F. Bathen
    • , Olav Engebråten
    • , Gry Aarum Geitvik
    • , Anita Langerød
    • , Rolf Kåresen
    • , Gunhild Mari Mælandsmo
    • , Ole Christian Lingjærde
    • , Helle Kristine Skjerven
    • , Daehoon Park
    • , Britt Fritzman
    • , Arnoldo Frigessi
    • , Kristine Kleivi Sahlberg
    • , Therese Sørlie
    • , Hege G. Russnes
    • , Bjørn Naume
    •  & Vessela N. Kristensen
  • Article
    | Open Access

    LRIG1 is a tumour suppressor in several cancers. Here, the authors show that androgen receptor directly transactivates LRIG1 which then antagonises ERBB signalling and c-Myc expression to inhibit prostate tumorigenesis.

    • Qiuhui Li
    • , Bigang Liu
    • , Hsueh-Ping Chao
    • , Yibing Ji
    • , Yue Lu
    • , Rashid Mehmood
    • , Collene Jeter
    • , Taiping Chen
    • , John R. Moore
    • , Wenqian Li
    • , Can Liu
    • , Kiera Rycaj
    • , Amanda Tracz
    • , Jason Kirk
    • , Tammy Calhoun-Davis
    • , Jie Xiong
    • , Qu Deng
    • , Jiaoti Huang
    • , Barbara A. Foster
    • , Abhiram Gokhale
    • , Xin Chen
    •  & Dean G. Tang
  • Article
    | Open Access

    Oncogenic exosomes can circulate in the blood, but their selective removal has not been possible. Here the authors show that aptamer-functionalised mesoporous silica nanoparticles can find to a specific population of circulating exosomes and eliminate them via the hepatobiliary route.

    • Xiaodong Xie
    • , Huifang Nie
    • , Yu Zhou
    • , Shu Lian
    • , Hao Mei
    • , Yusheng Lu
    • , Haiyan Dong
    • , Fengqiao Li
    • , Tao Li
    • , Bifei Li
    • , Jie Wang
    • , Min Lin
    • , Chaihung Wang
    • , Jingwei Shao
    • , Yu Gao
    • , Jianming Chen
    • , Fangwei Xie
    •  & Lee Jia
  • Article
    | Open Access

    Pre-malignant cells harbouring oncogenic mutations can populate and spread throughout a tissue. Here, using a rainbow mouse system, the authors explore how clonal expansion in the mouse intestine might explain high levels of intra-tumoural heterogeneity observed in the disease.

    • Peter G. Boone
    • , Lauren K. Rochelle
    • , Joshua D. Ginzel
    • , Veronica Lubkov
    • , Wendy L. Roberts
    • , P. J. Nicholls
    • , Cheryl Bock
    • , Mei Lang Flowers
    • , Richard J. von Furstenberg
    • , Barry R. Stripp
    • , Pankaj Agarwal
    • , Alexander D. Borowsky
    • , Robert D. Cardiff
    • , Larry S. Barak
    • , Marc G. Caron
    • , H. Kim Lyerly
    •  & Joshua C. Snyder
  • Article
    | Open Access

    Gemcitabine is used to treat gallbaldder cancer but patient responses are variable. Here, the authors use a genome-wide CRISPR screen and identify the translational elongator protein ELP5 as a protein that is important for mediating gemcitabine-induced apoptosis.

    • Sunwang Xu
    • , Ming Zhan
    • , Cen Jiang
    • , Min He
    • , Linhua Yang
    • , Hui Shen
    • , Shuai Huang
    • , Xince Huang
    • , Ruirong Lin
    • , Yongheng Shi
    • , Qiang Liu
    • , Wei Chen
    • , Man Mohan
    •  & Jian Wang
  • Article
    | Open Access

    Many cancer cells have increased glucose consumption compared to normal cells, a feature that can be exploited therapeutically. Here, the authors carry out a chemical screen and identify compounds that selectively blocks glucose metabolism in non-small-cell lung cancer cell lines.

    • Chiara Ghezzi
    • , Alicia Wong
    • , Bao Ying Chen
    • , Bernard Ribalet
    • , Robert Damoiseaux
    •  & Peter M. Clark
  • Article
    | Open Access

    Histology data exists for many cancer samples and the ability to automatically image this data may provide prognostic information. Here, the authors generated an algorithm to measure tumour infiltrating lymphocytes in melanoma histology specimens and show that the ratio of these immune cells to tumour cells has prognostic value.

    • Balazs Acs
    • , Fahad Shabbir Ahmed
    • , Swati Gupta
    • , Pok Fai Wong
    • , Robyn D. Gartrell
    • , Jaya Sarin Pradhan
    • , Emanuelle M. Rizk
    • , Bonnie Gould Rothberg
    • , Yvonne M. Saenger
    •  & David L. Rimm
  • Article
    | Open Access

    The genomic and immune landscape of pre-invasive lung adenocarcinoma is poorly understood. Here, the authors perform exome and transcriptome sequencing on precursor legions and invasive lung adenocarcinomas, identifying recurrently mutated genes in pre/minimally invasive cases, and arm level alteration events linked to immune infiltration.

    • Haiquan Chen
    • , Jian Carrot-Zhang
    • , Yue Zhao
    • , Haichuan Hu
    • , Samuel S. Freeman
    • , Su Yu
    • , Gavin Ha
    • , Alison M. Taylor
    • , Ashton C. Berger
    • , Lindsay Westlake
    • , Yuanting Zheng
    • , Jiyang Zhang
    • , Aruna Ramachandran
    • , Qiang Zheng
    • , Yunjian Pan
    • , Difan Zheng
    • , Shanbo Zheng
    • , Chao Cheng
    • , Muyu Kuang
    • , Xiaoyan Zhou
    • , Yang Zhang
    • , Hang Li
    • , Ting Ye
    • , Yuan Ma
    • , Zhendong Gao
    • , Xiaoting Tao
    • , Han Han
    • , Jun Shang
    • , Ying Yu
    • , Ding Bao
    • , Yechao Huang
    • , Xiangnan Li
    • , Yawei Zhang
    • , Jiaqing Xiang
    • , Yihua Sun
    • , Yuan Li
    • , Andrew D. Cherniack
    • , Joshua D. Campbell
    • , Leming Shi
    •  & Matthew Meyerson
  • Article
    | Open Access

    Acute Myeloid Leukemia (AML) develops following multiple mutations of differing impact. Here, the authors show that activating mutations of CSF3R co-operate with loss-of-function mutations of CEBPA to promote AML development through an enhancer-dependent mechanism.

    • Theodore P. Braun
    • , Mariam Okhovat
    • , Cody Coblentz
    • , Sarah A. Carratt
    • , Amy Foley
    • , Zachary Schonrock
    • , Brittany M. Smith
    • , Kimberly Nevonen
    • , Brett Davis
    • , Brianna Garcia
    • , Dorian LaTocha
    • , Benjamin R. Weeder
    • , Michal R. Grzadkowski
    • , Joey C. Estabrook
    • , Hannah G. Manning
    • , Kevin Watanabe-Smith
    • , Sophia Jeng
    • , Jenny L. Smith
    • , Amanda R. Leonti
    • , Rhonda E. Ries
    • , Shannon McWeeney
    • , Cristina Di Genua
    • , Roy Drissen
    • , Claus Nerlov
    • , Soheil Meshinchi
    • , Lucia Carbone
    • , Brian J. Druker
    •  & Julia E. Maxson
  • Article
    | Open Access

    Radiofrequency ablation is used to treat metastatic colorectal cancer. In this study, the authors show that incomplete ablation of tumours results in metastases and show in mouse models that the chemokine CCL2 recruits myeloid cells to the partially ablated tumours, which can block T cell function.

    • Liangrong Shi
    • , Junjun Wang
    • , Nianhua Ding
    • , Yi Zhang
    • , Yibei Zhu
    • , Shunli Dong
    • , Xiaohui Wang
    • , Changli Peng
    • , Chunhui Zhou
    • , Ledu Zhou
    • , Xiaodong Li
    • , Hongbing Shi
    • , Wei Wu
    • , Xueyin Long
    • , Changping Wu
    •  & Weihua Liao
  • Article
    | Open Access

    The evolutionary trade-offs faced by tumors are poorly understood, yet could contribute to the molecular diversity of cancer. Here, the authors analyze the diversity of genetic alterations, genes expressed and drug sensitivities among solid tumors to explore what evolutionary trade-offs may explain the molecular diversity of tumors.

    • Jean Hausser
    • , Pablo Szekely
    • , Noam Bar
    • , Anat Zimmer
    • , Hila Sheftel
    • , Carlos Caldas
    •  & Uri Alon
  • Article
    | Open Access

    Anaplastic lymphoma kinase (ALK) inhibitors are currently being considered in neuroblastoma (NB), but its acquired resistance is reported in non-small cell lung cancers. Here, the authors have found PIM1 overexpression decreases sensitivity to ALK inhibitors in NB and combined ALK and PIM1 inhibition enhances anti-tumour efficacy in vitro and in PDX models.

    • Ricky M. Trigg
    • , Liam C. Lee
    • , Nina Prokoph
    • , Leila Jahangiri
    • , C. Patrick Reynolds
    • , G. A. Amos Burke
    • , Nicola A. Probst
    • , Miaojun Han
    • , Jamie D. Matthews
    • , Hong Kai Lim
    • , Eleanor Manners
    • , Sonia Martinez
    • , Joaquin Pastor
    • , Carmen Blanco-Aparicio
    • , Olaf Merkel
    • , Ines Garces de los Fayos Alonso
    • , Petra Kodajova
    • , Simone Tangermann
    • , Sandra Högler
    • , Ji Luo
    • , Lukas Kenner
    •  & Suzanne D. Turner
  • Article
    | Open Access

    Tissue context can dictate why a gene can have seemingly opposing functions in different settings. ELF3 is tumor suppressive in many cancers of epithelial origin but in lung cancer, the authors describe an oncogenic role in the adenocarcinoma histology of non-small cell lung cancer.

    • Katey S. S. Enfield
    • , Erin A. Marshall
    • , Christine Anderson
    • , Kevin W. Ng
    • , Sara Rahmati
    • , Zhaolin Xu
    • , Megan Fuller
    • , Katy Milne
    • , Daniel Lu
    • , Rocky Shi
    • , David A. Rowbotham
    • , Daiana D. Becker-Santos
    • , Fraser D. Johnson
    • , John C. English
    • , Calum E. MacAulay
    • , Stephen Lam
    • , William W. Lockwood
    • , Raj Chari
    • , Aly Karsan
    • , Igor Jurisica
    •  & Wan L. Lam
  • Article
    | Open Access

    The human ATP-binding cassette transporter ABCG2 plays critical roles in anticancer resistance but the molecular mechanism of ABCG2-mediated substrate transport remains enigmatic. Here authors use extensive mutagenesis and molecular dynamics simulations to reveal a mechanistic basis for the function of the di-leucine valve and the roof organization in the transport cycle.

    • Narakorn Khunweeraphong
    • , Daniel Szöllősi
    • , Thomas Stockner
    •  & Karl Kuchler
  • Article
    | Open Access

    Identification of clinically relevant gene expression signatures for cancer stratification remains challenging. Here, the authors introduce a flexible nonlinear signal superposition model that enables dissection of large gene expression data sets into signatures and extraction of gene interactions.

    • Michael Grau
    • , Georg Lenz
    •  & Peter Lenz
  • Article
    | Open Access

    In pancreatic cancer the Kras and Trp53 transgene driven KPC mouse model is used to experimentally study disease processes. Here, the authors analyse tumour evolution within the KPC model, finding both linear and branched evolution and highlighting the utility of this model in mechanistic research of tumour evolution.

    • Noushin Niknafs
    • , Yi Zhong
    • , John Alec Moral
    • , Lance Zhang
    • , Melody Xiaoshan Shao
    • , April Lo
    • , Alvin Makohon-Moore
    • , Christine A. Iacobuzio-Donahue
    •  & Rachel Karchin
  • Perspective
    | Open Access

    Dendritic cells (DCs) have been explored as a promising strategy for cancer immunotherapy. In this Perspective, the authors discuss the different types of DCs and their therapeutic potential in the context of vaccines for personalized cancer therapy.

    • Caleb R. Perez
    •  & Michele De Palma
  • Article
    | Open Access

    The invasion of epithelial tumours often depends on the epithelial-mesenchymal transition. Here, the authors report that intracellular activation of thyroid hormone by the D2 deiodinase enzyme promotes invasion and progression of squamous cell carcinoma by transcriptionally up-regulating ZEB-1.

    • Caterina Miro
    • , Emery Di Cicco
    • , Raffaele Ambrosio
    • , Giuseppina Mancino
    • , Daniela Di Girolamo
    • , Annunziata Gaetana Cicatiello
    • , Serena Sagliocchi
    • , Annarita Nappi
    • , Maria Angela De Stefano
    • , Cristina Luongo
    • , Dario Antonini
    • , Feliciano Visconte
    • , Silvia Varricchio
    • , Gennaro Ilardi
    • , Luigi Del Vecchio
    • , Stefania Staibano
    • , Anita Boelen
    • , Cedric Blanpain
    • , Caterina Missero
    • , Domenico Salvatore
    •  & Monica Dentice
  • Article
    | Open Access

    The efficacy of tumour starvation therapy is limited by lack of persistent tumour suppression, tumour metastasis and recurrence. Here, the authors report biocompatible gold nanorods and thermal-sensitive hydrogel to promote narrowing of blood vessels and show this to reduce tumour growth and metastasis.

    • Kun Zhang
    • , Yan Fang
    • , Yaping He
    • , Haohao Yin
    • , Xin Guan
    • , Yinying Pu
    • , Bangguo Zhou
    • , Wenwen Yue
    • , Weiwei Ren
    • , Dou Du
    • , Hongyan Li
    • , Chang Liu
    • , Liping Sun
    • , Yu Chen
    •  & Huixiong Xu
  • Article
    | Open Access

    There is disproportionally high cancer prevalence in males. Here, the authors analyse the tumour suppressor p53 in sporadic cancers, highlighting a higher incidence of its mutation in males. Males are further disadvantaged by a failure to shield against the expression of damaged X-linked genes in p53-networks. These factors likely contribute to sex-disparity.

    • Sue Haupt
    • , Franco Caramia
    • , Alan Herschtal
    • , Thierry Soussi
    • , Guillermina Lozano
    • , Hu Chen
    • , Han Liang
    • , Terence P. Speed
    •  & Ygal Haupt
  • Article
    | Open Access

    The restriction of appropriate tumour-specific antigens is a current limitation for T cell-engaging immunotherapy. Here, the authors have designed a new system constituted by two halve antibodies, which engage T cells once binding to two different antigens, to specifically eliminate double positive cells in preclinical leukemia and breast cancer mouse models.

    • Agnes Banaszek
    • , Thomas G. P. Bumm
    • , Boris Nowotny
    • , Maria Geis
    • , Kim Jacob
    • , Matthias Wölfl
    • , Johannes Trebing
    • , Kirstin Kucka
    • , Dina Kouhestani
    • , Tea Gogishvili
    • , Bastian Krenz
    • , Justina Lutz
    • , Leo Rasche
    • , Dirk Hönemann
    • , Hannes Neuweiler
    • , Julia C. Heiby
    • , Ralf C. Bargou
    • , Harald Wajant
    • , Hermann Einsele
    • , Gert Riethmüller
    •  & Gernot Stuhler
  • Article
    | Open Access

    It is unclear whether fallopian tube epithelium or ovarian surface epithelium is the cell-of-origin of high grade serous ovarian carcinoma (HGSOC). Here the authors report a dualistic origin for HGSOC using genetically engineered mouse models and observe differential chemotherapy sensitivity depending on the cell-of-origin.

    • Shuang Zhang
    • , Igor Dolgalev
    • , Tao Zhang
    • , Hao Ran
    • , Douglas A. Levine
    •  & Benjamin G. Neel
  • Article
    | Open Access

    Several cancers harbour mutant p53 and express higher levels of p53-derived peptide-MHCs. Here, the authors report affinity matured human antibody, P1C1TM, specific for the p53125-134 peptide in complex with the HLA-A24 class I MHC molecule and show its efficacy and specificity for mutant p53 expressing tumours.

    • Lionel Low
    • , Angeline Goh
    • , Joanna Koh
    • , Samantha Lim
    •  & Cheng-I Wang
  • Article
    | Open Access

    Stepwise acquisition of mutations gives rise to myelodysplastic syndrome (MDS) in older adults. Here, the authors infer the clonal hierarchy of 1809 MDS patients, revealing insights into the evolution of dominant/secondary mutations and how these impact clinical phenotypes like leukemic progression and therapy response.

    • Yasunobu Nagata
    • , Hideki Makishima
    • , Cassandra M. Kerr
    • , Bartlomiej P. Przychodzen
    • , Mai Aly
    • , Abhinav Goyal
    • , Hassan Awada
    • , Mohammad Fahad Asad
    • , Teodora Kuzmanovic
    • , Hiromichi Suzuki
    • , Tetsuichi Yoshizato
    • , Kenichi Yoshida
    • , Kenichi Chiba
    • , Hiroko Tanaka
    • , Yuichi Shiraishi
    • , Satoru Miyano
    • , Sudipto Mukherjee
    • , Thomas LaFramboise
    • , Aziz Nazha
    • , Mikkael A. Sekeres
    • , Tomas Radivoyevitch
    • , Torsten Haferlach
    • , Seishi Ogawa
    •  & Jaroslaw P. Maciejewski
  • Article
    | Open Access

    LncRNAs at the HOX gene locus are increased in expression in NPM1 mutant acute myeloid leukemia. In this study, the authors show that one such lncRNA, HOX3B-AS3, has a role in regulating gene transcription and protein synthesis in leukemia cells.

    • Dimitrios Papaioannou
    • , Andreas Petri
    • , Oliver M. Dovey
    • , Sara Terreri
    • , Eric Wang
    • , Frances A. Collins
    • , Lauren A. Woodward
    • , Allison E. Walker
    • , Deedra Nicolet
    • , Felice Pepe
    • , Prasanthi Kumchala
    • , Marius Bill
    • , Christopher J. Walker
    • , Malith Karunasiri
    • , Krzysztof Mrózek
    • , Miranda L. Gardner
    • , Virginia Camilotto
    • , Nina Zitzer
    • , Jonathan L. Cooper
    • , Xiongwei Cai
    • , Xiaoqing Rong-Mullins
    • , Jessica Kohlschmidt
    • , Kellie J. Archer
    • , Michael A. Freitas
    • , Yi Zheng
    • , Robert J. Lee
    • , Iannis Aifantis
    • , George Vassiliou
    • , Guramrit Singh
    • , Sakari Kauppinen
    • , Clara D. Bloomfield
    • , Adrienne M. Dorrance
    •  & Ramiro Garzon
  • Article
    | Open Access

    The regenerating islet-derived (REG) protein family suppresses cell death and promotes cell proliferation. Here the authors report that the lncRNA REG1CP forms an RNA–DNA triplex at the promoter of REG3A gene to increase its expression.

    • Hamed Yari
    • , Lei Jin
    • , Liu Teng
    • , Yufang Wang
    • , Yongyan Wu
    • , Guang Zhi Liu
    • , Wei Gao
    • , Jin Liang
    • , Yanfeng Xi
    • , Yu Chen Feng
    • , Chunming Zhang
    • , Yuan Yuan Zhang
    • , Hessam Tabatabaee
    • , Ting La
    • , Rui Hong Yang
    • , Fu Hua Wang
    • , Xu Guang Yan
    • , Margaret Farrelly
    • , Rodney Scott
    • , Tao Liu
    • , Rick F. Thorne
    • , Su Tang Guo
    •  & Xu Dong Zhang
  • Article
    | Open Access

    B-cell acute lymphoblastic leukaemia (B-ALL) is a common childhood cancer. Here, the authors conducted a meta-analysis with four genome-wide association studies, totalling 5,321 cases and 16,666 controls of European descent, identifying B-ALL risk loci, whose integration with epigenomic profiling indicates cell-cycle and B-cell development deregulation as central mechanisms in B-ALL susceptibility, often in a subtype-specific fashion.

    • Jayaram Vijayakrishnan
    • , Maoxiang Qian
    • , James B. Studd
    • , Wenjian Yang
    • , Ben Kinnersley
    • , Philip J. Law
    • , Peter Broderick
    • , Elizabeth A. Raetz
    • , James Allan
    • , Ching-Hon Pui
    • , Ajay Vora
    • , William E. Evans
    • , Anthony Moorman
    • , Allen Yeoh
    • , Wentao Yang
    • , Chunliang Li
    • , Claus R. Bartram
    • , Charles G. Mullighan
    • , Martin Zimmerman
    • , Stephen P. Hunger
    • , Martin Schrappe
    • , Mary V. Relling
    • , Martin Stanulla
    • , Mignon L. Loh
    • , Richard S. Houlston
    •  & Jun J. Yang
  • Article
    | Open Access

    PDLIM2 is repressed epigenetically in lung cancers, which are frequently resistant to anti-PD-1/PD-L1 and chemotherapy. Here, the authors describe the mechanism through which epigenetic restoration of PDLIM2 synergises with anti-PD-1 and chemotherapy in lung cancers.

    • Fan Sun
    • , Liwen Li
    • , Pengrong Yan
    • , Jingjiao Zhou
    • , Steven D. Shapiro
    • , Gutian Xiao
    •  & Zhaoxia Qu
  • Article
    | Open Access

    The ATR pathway is active during DNA replication stress to maintain genome stability. Here the authors reveal the role of the zinc finger containing protein 161 (ZFP161) to facilitate replication fork stability by acting as a scaffold to facilitate the interaction between RPA and ATR/ATRIP.

    • Wootae Kim
    • , Fei Zhao
    • , Rentian Wu
    • , Sisi Qin
    • , Somaira Nowsheen
    • , Jinzhou Huang
    • , Qin Zhou
    • , Yuping Chen
    • , Min Deng
    • , Guijie Guo
    • , Kuntian Luo
    • , Zhenkun Lou
    •  & Jian Yuan
  • Article
    | Open Access

    Detecting genomic abnormalities in metastatic castration-resistant prostate cancer (mCRPC) may impact clinical treatment. Here, the authors present whole-genome sequencing of metastatic biopsies from 197 mCRPC patients, highlighting the landscape of microsatellite stability, homologous repair deficiency, and other genomic subgroups.

    • Lisanne F. van Dessel
    • , Job van Riet
    • , Minke Smits
    • , Yanyun Zhu
    • , Paul Hamberg
    • , Michiel S. van der Heijden
    • , Andries M. Bergman
    • , Inge M. van Oort
    • , Ronald de Wit
    • , Emile E. Voest
    • , Neeltje Steeghs
    • , Takafumi N. Yamaguchi
    • , Julie Livingstone
    • , Paul C. Boutros
    • , John W. M. Martens
    • , Stefan Sleijfer
    • , Edwin Cuppen
    • , Wilbert Zwart
    • , Harmen J. G. van de Werken
    • , Niven Mehra
    •  & Martijn P. Lolkema
  • Article
    | Open Access

    The ERK signalling pathway is activated in many cancers, however ERK1 and ERK2 are difficult to target pharmacologically. Here, the authors identify a small molecule inhibitor that binds covalently to the D-recruitment site of ERK and induces cell death and reduces tumour growth in mice.

    • Tamer S. Kaoud
    • , William H. Johnson
    • , Nancy D. Ebelt
    • , Andrea Piserchio
    • , Diana Zamora-Olivares
    • , Sabrina X. Van Ravenstein
    • , Jacey R. Pridgen
    • , Ramakrishna Edupuganti
    • , Rachel Sammons
    • , Micael Cano
    • , Mangalika Warthaka
    • , Matthew Harger
    • , Clint D. J. Tavares
    • , Jihyun Park
    • , Mohamed F. Radwan
    • , Pengyu Ren
    • , Eric V. Anslyn
    • , Kenneth Y. Tsai
    • , Ranajeet Ghose
    •  & Kevin N. Dalby
  • Article
    | Open Access

    Treatment with demethylation agents can reactivate transposable elements. Here in glioblastoma, the authors also show that this is accompanied by de novo presentation of TE-derived peptides on MHC class I molecules.

    • Yu Kong
    • , Christopher M. Rose
    • , Ashley A. Cass
    • , Alexander G. Williams
    • , Martine Darwish
    • , Steve Lianoglou
    • , Peter M. Haverty
    • , Ann-Jay Tong
    • , Craig Blanchette
    • , Matthew L. Albert
    • , Ira Mellman
    • , Richard Bourgon
    • , John Greally
    • , Suchit Jhunjhunwala
    •  & Haiyin Chen-Harris
  • Article
    | Open Access

    There is a need to further improve the efficacy of biodegradable wafers used in surgically treated brain tumors. Here, the authors report a flexible, biodegradable wireless device capable of adhesion to surgical site for optimal drug delivery upon mild-thermic actuation and report therapeutic efficacy in mouse and canine tumor models.

    • Jongha Lee
    • , Hye Rim Cho
    • , Gi Doo Cha
    • , Hyunseon Seo
    • , Seunghyun Lee
    • , Chul-Kee Park
    • , Jin Wook Kim
    • , Shutao Qiao
    • , Liu Wang
    • , Dayoung Kang
    • , Taegyu Kang
    • , Tomotsugu Ichikawa
    • , Jonghoon Kim
    • , Hakyong Lee
    • , Woongchan Lee
    • , Sanghoek Kim
    • , Soon-Tae Lee
    • , Nanshu Lu
    • , Taeghwan Hyeon
    • , Seung Hong Choi
    •  & Dae-Hyeong Kim