Oncology

  • 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

    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

    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

    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

    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

    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

    The gut microbiota has been reported to regulate the efficacy of cancer therapy. Here, the authors show that short-chain fatty acids, which are generated through bacterial fermentation, increases immune tolerance leading to resistance to anti-CTLA-4 immunotherapy in mice and patients with metastatic melanoma.

    • Clélia Coutzac
    • , Jean-Mehdi Jouniaux
    • , Angelo Paci
    • , Julien Schmidt
    • , Domenico Mallardo
    • , Atmane Seck
    • , Vahe Asvatourian
    • , Lydie Cassard
    • , Patrick Saulnier
    • , Ludovic Lacroix
    • , Paul-Louis Woerther
    • , Aurore Vozy
    • , Marie Naigeon
    • , Laetitia Nebot-Bral
    • , Mélanie Desbois
    • , Ester Simeone
    • , Christine Mateus
    • , Lisa Boselli
    • , Jonathan Grivel
    • , Emilie Soularue
    • , Patricia Lepage
    • , Franck Carbonnel
    • , Paolo Antonio Ascierto
    • , Caroline Robert
    •  & Nathalie Chaput
  • Article
    | Open Access

    Immune checkpoint inhibitors have limited efficacy in tumors with lower mutational burden and non-permissive microenvironment. Here, the authors show that combining MEK inhibition with an agonist anti-CD40 immunostimulatory antibody improves antitumor treatment by inducing immunogenic changes in the tumor microenvironment.

    • Daniel Baumann
    • , Tanja Hägele
    • , Julian Mochayedi
    • , Jennifer Drebant
    • , Caroline Vent
    • , Sven Blobner
    • , Julia Han Noll
    • , Irena Nickel
    • , Corinna Schumacher
    • , Sophie Luise Boos
    • , Aline Sophie Daniel
    • , Susann Wendler
    • , Michael Volkmar
    • , Oliver Strobel
    •  & Rienk Offringa
  • Article
    | Open Access

    The cell adhesion molecule E-selectin regulates haematopoietic stem cell self-renewal in the bone marrow vascular niche. Here, the authors show E-selectin adhesion directly induces survival signaling in acute myeloid leukaemia and therapeutic inhibition improves chemotherapy outcomes in mice.

    • Valerie Barbier
    • , Johanna Erbani
    • , Corrine Fiveash
    • , Julie M. Davies
    • , Joshua Tay
    • , Michael R. Tallack
    • , Jessica Lowe
    • , John L. Magnani
    • , Diwakar R. Pattabiraman
    • , Andrew C. Perkins
    • , Jessica Lisle
    • , John E. J. Rasko
    • , Jean-Pierre Levesque
    •  & Ingrid G. Winkler
  • Article
    | Open Access

    The identification of mRNA targets for RNA binding proteins (RBP) in stem cells is difficult due to the limited number of available cells. Here, as a proof-of-principle, the authors adapt the HyperTRIBE method to find that an RBP, MSI2, has increased RNA binding in leukemic compared with normal stem cells for selective regulation of oncogenic genes.

    • Diu T. T. Nguyen
    • , Yuheng Lu
    • , Karen L. Chu
    • , Xuejing Yang
    • , Sun-Mi Park
    • , Zi-Ning Choo
    • , Christopher R. Chin
    • , Camila Prieto
    • , Alexandra Schurer
    • , Ersilia Barin
    • , Angela M. Savino
    • , Saroj Gourkanti
    • , Payal Patel
    • , Ly P. Vu
    • , Christina S. Leslie
    •  & Michael G. Kharas
  • Article
    | Open Access

    The advancement of upper tract urothelial carcinoma (UTUC) research is hampered by the lack of disease-specific models. Here, the authors report patient derived xenograft and cell line models of UTUC, and show that these models retain the genomic and biological heterogeneity of human disease.

    • Kwanghee Kim
    • , Wenhuo Hu
    • , François Audenet
    • , Nima Almassi
    • , Aphrothiti J. Hanrahan
    • , Katie Murray
    • , Aditya Bagrodia
    • , Nathan Wong
    • , Timothy N. Clinton
    • , Shawn Dason
    • , Vishnu Mohan
    • , Sylvia Jebiwott
    • , Karan Nagar
    • , Jianjiong Gao
    • , Alex Penson
    • , Chris Hughes
    • , Benjamin Gordon
    • , Ziyu Chen
    • , Yiyu Dong
    • , Philip A. Watson
    • , Ricardo Alvim
    • , Arijh Elzein
    • , Sizhi P. Gao
    • , Emiliano Cocco
    • , Alessandro D. Santin
    • , Irina Ostrovnaya
    • , James J. Hsieh
    • , Irit Sagi
    • , Eugene J. Pietzak
    • , A. Ari Hakimi
    • , Jonathan E. Rosenberg
    • , Gopa Iyer
    • , Herbert A. Vargas
    • , Maurizio Scaltriti
    • , Hikmat Al-Ahmadie
    • , David B. Solit
    •  & Jonathan A. Coleman
  • Article
    | Open Access

    Molecular analysis of archival formalin-fixed clinical tissues can be difficult. Here, researchers have developed MethCORR, an approach that infers gene expression from DNA methylation data and use the approach for molecular characterization and prognostication of colorectal cancer using archival samples.

    • Trine B. Mattesen
    • , Mads H. Rasmussen
    • , Juan Sandoval
    • , Halit Ongen
    • , Sigrid S. Árnadóttir
    • , Josephine Gladov
    • , Anna Martinez-Cardus
    • , Manuel Castro de Moura
    • , Anders H. Madsen
    • , Søren Laurberg
    • , Emmanouil T. Dermitzakis
    • , Manel Esteller
    • , Claus L. Andersen
    •  & Jesper B. Bramsen
  • Article
    | Open Access

    Evolutionary steering uses therapies to control tumour evolution by exploiting trade-offs. Here, using a barcoding approach applied to large cell populations, the authors explore evolutionary steering in lung cancer cells treated with EGFR inhibitors.

    • Ahmet Acar
    • , Daniel Nichol
    • , Javier Fernandez-Mateos
    • , George D. Cresswell
    • , Iros Barozzi
    • , Sung Pil Hong
    • , Nicholas Trahearn
    • , Inmaculada Spiteri
    • , Mark Stubbs
    • , Rosemary Burke
    • , Adam Stewart
    • , Giulio Caravagna
    • , Benjamin Werner
    • , Georgios Vlachogiannis
    • , Carlo C. Maley
    • , Luca Magnani
    • , Nicola Valeri
    • , Udai Banerji
    •  & Andrea Sottoriva
  • Article
    | Open Access

    Abscopal responses in patients and preclinical models following radiation therapy are rare. Here the authors show that, in murine tumor models, reducing adrenergic stress or β2-adrenergic receptor signalling not only improves control of the irradiated tumor but significantly increases abscopal events.

    • Minhui Chen
    • , Guanxi Qiao
    • , Bonnie L. Hylander
    • , Hemn Mohammadpour
    • , Xiang-Yang Wang
    • , John R. Subjeck
    • , Anurag K. Singh
    •  & Elizabeth A. Repasky
  • Article
    | Open Access

    Pineoblastoma is a rare pediatric cancer. Here, the authors present inactivation of Rb plus p53 via a WAP-Cre transgene induces metastatic pineoblastoma resembling human disease, and using this model, predict tricyclic antidepressants as a potential therapy for pineoblastoma, supported by their pre-clinical model.

    • Philip E. D. Chung
    • , Deena M. A. Gendoo
    • , Ronak Ghanbari-Azarnier
    • , Jeff C. Liu
    • , Zhe Jiang
    • , Jennifer Tsui
    • , Dong-Yu Wang
    • , Xiao Xiao
    • , Bryan Li
    • , Adrian Dubuc
    • , David Shih
    • , Marc Remke
    • , Ben Ho
    • , Livia Garzia
    • , Yaacov Ben-David
    • , Seok-Gu Kang
    • , Sidney Croul
    • , Benjamin Haibe-Kains
    • , Annie Huang
    • , Michael D. Taylor
    •  & Eldad Zacksenhaus
  • Article
    | Open Access

    Cutaneous gamma-delta T cell lymphomas are rare but aggressive cancers. Here, by DNA, RNA and T cell receptor sequencing, the authors elucidate the molecular ontogeny by revising the cell of origin and identifying potentially targetable mutations.

    • Jay Daniels
    • , Peter G. Doukas
    • , Maria E. Martinez Escala
    • , Kimberly G. Ringbloom
    • , David J. H. Shih
    • , Jingyi Yang
    • , Kyle Tegtmeyer
    • , Joonhee Park
    • , Jane J. Thomas
    • , Mehmet E. Selli
    • , Can Altunbulakli
    • , Ragul Gowthaman
    • , Samuel H. Mo
    • , Balaji Jothishankar
    • , David R. Pease
    • , Barbara Pro
    • , Farah R. Abdulla
    • , Christopher Shea
    • , Nidhi Sahni
    • , Alejandro A. Gru
    • , Brian G. Pierce
    • , Abner Louissaint Jr
    • , Joan Guitart
    •  & Jaehyuk Choi
  • Article
    | Open Access

    Why the carcinogen urethane causes only lung tumours driven by a specific oncogenic mutation in just one Ras gene in mice is unclear. Here, the authors capture mutations immediately after urethane exposure and show that the sequence specificity of mutagenesis, transcriptional status, and Ras genetic loci may all contribute to this specificity.

    • Siqi Li
    • , David M. MacAlpine
    •  & Christopher M. Counter
  • Article
    | Open Access

    PD-L1 is highly expressed in triple-negative breast cancers (TNBC). Here, the authors show that nucleophosmin 1 (NPM1) transcriptionally activates PD-L1 expression and inhibits T cell activity in TNBC.

    • Ge Qin
    • , Xin Wang
    • , Shubiao Ye
    • , Yizhuo Li
    • , Miao Chen
    • , Shusen Wang
    • , Tao Qin
    • , Changlin Zhang
    • , Yixin Li
    • , Qian Long
    • , Huabin Hu
    • , Dingbo Shi
    • , Jiaping Li
    • , Kai Zhang
    • , Qinglian Zhai
    • , Yanlai Tang
    • , Tiebang Kang
    • , Ping Lan
    • , Fangyun Xie
    • , Jianjun Lu
    •  & Wuguo Deng
  • Article
    | Open Access

    Oncogenic Ras mutations are common drivers in myeloid leukemia. Here, the authors show in patient cells and in mice that oncogenic K-Ras activates NLRP3 inflammasome to drive myeloproliferation, which can be reversed by genetic or pharmacologic NLRP3 blockade.

    • Shaima’a Hamarsheh
    • , Lena Osswald
    • , Benedikt S. Saller
    • , Susanne Unger
    • , Donatella De Feo
    • , Janaki Manoja Vinnakota
    • , Martina Konantz
    • , Franziska M. Uhl
    • , Heiko Becker
    • , Michael Lübbert
    • , Khalid Shoumariyeh
    • , Christoph Schürch
    • , Geoffroy Andrieux
    • , Nils Venhoff
    • , Annette Schmitt-Graeff
    • , Sandra Duquesne
    • , Dietmar Pfeifer
    • , Matthew A. Cooper
    • , Claudia Lengerke
    • , Melanie Boerries
    • , Justus Duyster
    • , Charlotte M. Niemeyer
    • , Miriam Erlacher
    • , Bruce R. Blazar
    • , Burkard Becher
    • , Olaf Groß
    • , Tilman Brummer
    •  & Robert Zeiser
  • Article
    | Open Access

    It is known that there are sex differences in the incidence and prognosis of certain cancers, including melanoma. In this study, the authors utilize a melanoma model to reveal that castrated mice have a higher metastatic burden associated with androgen dependent impaired neutrophil function.

    • Janet L. Markman
    • , Rebecca A. Porritt
    • , Daiko Wakita
    • , Malcolm E. Lane
    • , Daisy Martinon
    • , Magali Noval Rivas
    • , Michael Luu
    • , Edwin M. Posadas
    • , Timothy R. Crother
    •  & Moshe Arditi
  • Article
    | Open Access

    The MET receptor is frequently activated in cancer. Here, the authors show that in head and neck and lung squamous carcinoma, a polymorphic MET variant enhances binding to HER2, resulting in activation of HER2 signalling and progression of the cancers.

    • Li Ren Kong
    • , Nur Afiqah Binte Mohamed Salleh
    • , Richard Weijie Ong
    • , Tuan Zea Tan
    • , Nicholas L. Syn
    • , Robby Miguel Goh
    • , Chee Wai Fhu
    • , Daniel S. W. Tan
    • , N. Gopalakrishna Iyer
    • , Srinivasaraghavan Kannan
    • , Chandra S. Verma
    • , Yaw Chyn Lim
    • , Ross Soo
    • , Jingshan Ho
    • , Yiqing Huang
    • , Joline S. J. Lim
    • , Benedict Junrong Yan
    • , Min En Nga
    • , Seng Gee Lim
    • , H. Phillip Koeffler
    • , Soo Chin Lee
    • , Dennis Kappei
    • , Huynh The Hung
    •  & Boon Cher Goh
  • Article
    | Open Access

    Professional antigen presenting cells (APCs) are deterred from phagocytosing cancer cells that express CD47. Here, the authors show that in glioblastoma mouse models, temozolomide improves the phagocytosis effect of CD47 blockade in APCs and results in the activation of adaptive anti-tumour responses.

    • Christina A. von Roemeling
    • , Yifan Wang
    • , Yaqing Qie
    • , Hengfeng Yuan
    • , Hai Zhao
    • , Xiujie Liu
    • , Zhaogang Yang
    • , Mingming Yang
    • , Weiye Deng
    • , Katelyn A. Bruno
    • , Charles K. Chan
    • , Andrew S. Lee
    • , Stephen S. Rosenfeld
    • , Kyuson Yun
    • , Aaron J. Johnson
    • , Duane A. Mitchell
    • , Wen Jiang
    •  & Betty Y. S. Kim
  • Article
    | Open Access

    A Phase I/II trial previously revealed variable anti-tumor efficacy of the PARP inhibitor niraparib in combination with the PD-1 inhibitor pembrolizumab in platinum-resistant ovarian cancer patients. Here, the authors perform an integrated genomic and immunomics analysis of tumor samples from the same patients and find potential predictive biomarkers of response to such combination therapy.

    • Anniina Färkkilä
    • , Doga C. Gulhan
    • , Julia Casado
    • , Connor A. Jacobson
    • , Huy Nguyen
    • , Bose Kochupurakkal
    • , Zoltan Maliga
    • , Clarence Yapp
    • , Yu-An Chen
    • , Denis Schapiro
    • , Yinghui Zhou
    • , Julie R. Graham
    • , Bruce J. Dezube
    • , Pamela Munster
    • , Sandro Santagata
    • , Elizabeth Garcia
    • , Scott Rodig
    • , Ana Lako
    • , Dipanjan Chowdhury
    • , Geoffrey I. Shapiro
    • , Ursula A. Matulonis
    • , Peter J. Park
    • , Sampsa Hautaniemi
    • , Peter K. Sorger
    • , Elizabeth M. Swisher
    • , Alan D. D’Andrea
    •  & Panagiotis A. Konstantinopoulos
  • Article
    | Open Access

    Modern imaging techniques can detect cancer cells in the lymph nodes of cancer patients. In this study, the authors show that tumour related leukocytosis, a phenomenon where leukocytes are increased in number, can lead to the false positive detection of cancer cells in lymph nodes.

    • Seiji Mabuchi
    • , Naoko Komura
    • , Tomoyuki Sasano
    • , Kotaro Shimura
    • , Eriko Yokoi
    • , Katsumi Kozasa
    • , Hiromasa Kuroda
    • , Ryoko Takahashi
    • , Mahiru Kawano
    • , Yuri Matsumoto
    • , Hiroki Kato
    • , Jun Hatazawa
    •  & Tadashi Kimura
  • Article
    | Open Access

    Oncolytic viruses can activate tumor neoantigen-specific T cell responses. However, PD-L1 upregulation on tumor cells and immune cells leads to tumor resistance to this immunotherapy approach. Here, the authors develop an oncolytic virus which expresses both a PD-L1 inhibitor and GM-CSF which allows an improved tumor neoantigen-specific T cell response in preclinical models.

    • Guan Wang
    • , Xi Kang
    • , Katherine S. Chen
    • , Tiffany Jehng
    • , Lindsey Jones
    • , Jie Chen
    • , Xue F. Huang
    •  & Si-Yi Chen
  • Article
    | Open Access

    Alternate splicing of mRNA precursors has been linked to tumor development. Here the authors reveal a role of the E3 ligase RNF113A in spliceosome regulation affecting cell survival upon DNA damage.

    • Kateryna Shostak
    • , Zheshen Jiang
    • , Benoit Charloteaux
    • , Alice Mayer
    • , Yvette Habraken
    • , Lars Tharun
    • , Sebastian Klein
    • , Xinyi Xu
    • , Hong Quan Duong
    • , Andrii Vislovukh
    • , Pierre Close
    • , Alexandra Florin
    • , Florian Rambow
    • , Jean-Christophe Marine
    • , Reinhard Büttner
    •  & Alain Chariot
  • Article
    | Open Access

    Breast cancer is frequently diagnosed using ultrasound. Here, the authors show that, in addition to ultrasound, shear wave elastography can be used to diagnose breast cancer and, in conjunction with deep learning and radiomics, can predict whether the disease has spread to axillary lymph nodes.

    • Xueyi Zheng
    • , Zhao Yao
    • , Yini Huang
    • , Yanyan Yu
    • , Yun Wang
    • , Yubo Liu
    • , Rushuang Mao
    • , Fei Li
    • , Yang Xiao
    • , Yuanyuan Wang
    • , Yixin Hu
    • , Jinhua Yu
    •  & Jianhua Zhou
  • Article
    | Open Access

    Venetoclax monotherapy is effective in 40% of t(11:14) positive multiple myeloma (MM). Here, the authors show that electron transport chain complex I (CI) and complex II (CII) activity predict MM sensitivity to venetoclax, and inhibition of CI with IACS-010759 or CII with TTFA increase sensitivity.

    • Richa Bajpai
    • , Aditi Sharma
    • , Abhinav Achreja
    • , Claudia L. Edgar
    • , Changyong Wei
    • , Arusha A. Siddiqa
    • , Vikas A. Gupta
    • , Shannon M. Matulis
    • , Samuel K. McBrayer
    • , Anjali Mittal
    • , Manali Rupji
    • , Benjamin G. Barwick
    • , Sagar Lonial
    • , Ajay K. Nooka
    • , Lawrence H. Boise
    • , Deepak Nagrath
    •  & Mala Shanmugam
  • Article
    | Open Access

    Mechanisms regulating the formation of pre-metastatic niches remain poorly understood. Here, the authors show that ITGBL1-containing extracellular vesicles derived from primary colorectal cancer cells activate the production of inflammatory cytokines by resident fibroblasts in distant organs, promoting metastatic cancer growth.

    • Qing Ji
    • , Lihong Zhou
    • , Hua Sui
    • , Liu Yang
    • , Xinnan Wu
    • , Qing Song
    • , Ru Jia
    • , Ruixiao Li
    • , Jian Sun
    • , Ziyuan Wang
    • , Ningning Liu
    • , Yuanyuan Feng
    • , Xiaoting Sun
    • , Gang Cai
    • , Yu Feng
    • , Jianfeng Cai
    • , Yihai Cao
    • , Guoxiang Cai
    • , Yan Wang
    •  & Qi Li
  • Article
    | Open Access

    Tumors can overproduce pro-angiogenic ligands overcoming currently approved anti-angiogenic therapies and hindering their success. Here, the authors show that targeting phosphoinositide recycling during tumor angiogenesis harnesses the tumor’s own production of angiogenic ligands to deplete adjacent endothelial cells of the capacity to respond to these signals.

    • Amber N. Stratman
    • , Olivia M. Farrelly
    • , Constantinos M. Mikelis
    • , Mayumi F. Miller
    • , Zhiyong Wang
    • , Van N. Pham
    • , Andrew E. Davis
    • , Margaret C. Burns
    • , Sofia A. Pezoa
    • , Daniel Castranova
    • , Joseph J. Yano
    • , Tina M. Kilts
    • , George E. Davis
    • , J. Silvio Gutkind
    •  & Brant M. Weinstein
  • Article
    | Open Access

    Osteosarcoma is an aggressive tumour and little is known the mechanisms underpinning its highly metastatic nature. Here, the authors highlight a role for the CK1α/CBX4 axis in driving metastasis, suggesting that this pathway might be targeted for therapeutic benefit.

    • Xin Wang
    • , Ge Qin
    • , Xiaoting Liang
    • , Wen Wang
    • , Zhuo Wang
    • , Dan Liao
    • , Li Zhong
    • , Ruhua Zhang
    • , Yi-Xin Zeng
    • , Yuanzhong Wu
    •  & Tiebang Kang
  • Article
    | Open Access

    The efficacy of immune checkpoint inhibitors (ICI) in osteosarcoma has been limited. Here, the authors investigate the immunogenomic landscape of osteosarcoma, and integrated analyses highlight features related to a suppressed immune microenvironment.

    • Chia-Chin Wu
    • , Hannah C. Beird
    • , J. Andrew Livingston
    • , Shailesh Advani
    • , Akash Mitra
    • , Shaolong Cao
    • , Alexandre Reuben
    • , Davis Ingram
    • , Wei-Lien Wang
    • , Zhenlin Ju
    • , Cheuk Hong Leung
    • , Heather Lin
    • , Youyun Zheng
    • , Jason Roszik
    • , Wenyi Wang
    • , Shreyaskumar Patel
    • , Robert S. Benjamin
    • , Neeta Somaiah
    • , Anthony P. Conley
    • , Gordon B. Mills
    • , Patrick Hwu
    • , Richard Gorlick
    • , Alexander Lazar
    • , Najat C. Daw
    • , Valerae Lewis
    •  & P. Andrew Futreal
  • Article
    | Open Access

    Prostate cancer is often a multifocal disease but how best to manage this clinically remains unclear. Here, the authors report a single case study of a patient with two genetically diverse tumours which showed differential response to therapy.

    • Scott Wilkinson
    • , Stephanie A. Harmon
    • , Nicholas T. Terrigino
    • , Fatima Karzai
    • , Peter A. Pinto
    • , Ravi A. Madan
    • , David J. VanderWeele
    • , Ross Lake
    • , Rayann Atway
    • , John R. Bright
    • , Nicole V. Carrabba
    • , Shana Y. Trostel
    • , Rosina T. Lis
    • , Guinevere Chun
    • , James L. Gulley
    • , Maria J. Merino
    • , Peter L. Choyke
    • , Huihui Ye
    • , William L. Dahut
    • , Baris Turkbey
    •  & Adam G. Sowalsky
  • Article
    | Open Access

    High-grade serous ovarian carcinoma is often associated with TP53 mutation and chromosomal instability (CIN). Here, the authors generate ex vivo cultures from biopsies and ascites of patients and perform characterization to evaluate CIN mechanisms and compare drug sensitivity with patient responses.

    • Louisa Nelson
    • , Anthony Tighe
    • , Anya Golder
    • , Samantha Littler
    • , Bjorn Bakker
    • , Daniela Moralli
    • , Syed Murtuza Baker
    • , Ian J. Donaldson
    • , Diana C. J. Spierings
    • , René Wardenaar
    • , Bethanie Neale
    • , George J. Burghel
    • , Brett Winter-Roach
    • , Richard Edmondson
    • , Andrew R. Clamp
    • , Gordon C. Jayson
    • , Sudha Desai
    • , Catherine M. Green
    • , Andy Hayes
    • , Floris Foijer
    • , Robert D. Morgan
    •  & Stephen S. Taylor
  • Article
    | Open Access

    In somatic cells the mechanisms maintaining the chromosome ends are normally inactivated; however, cancer cells can re-activate these pathways to support continuous growth. Here, the authors characterize the telomeric landscapes across tumour types and identify genomic alterations associated with different telomere maintenance mechanisms.

    • Lina Sieverling
    • , Chen Hong
    • , Sandra D. Koser
    • , Philip Ginsbach
    • , Kortine Kleinheinz
    • , Barbara Hutter
    • , Delia M. Braun
    • , Isidro Cortés-Ciriano
    • , Ruibin Xi
    • , Rolf Kabbe
    • , Peter J. Park
    • , Roland Eils
    • , Matthias Schlesner
    • , Kadir C. Akdemir
    • , Eva G. Alvarez
    • , Adrian Baez-Ortega
    • , Rameen Beroukhim
    • , Paul C. Boutros
    • , David D. L. Bowtell
    • , Benedikt Brors
    • , Kathleen H. Burns
    • , Peter J. Campbell
    • , Kin Chan
    • , Ken Chen
    • , Isidro Cortés-Ciriano
    • , Ana Dueso-Barroso
    • , Andrew J. Dunford
    • , Paul A. Edwards
    • , Xavier Estivill
    • , Dariush Etemadmoghadam
    • , Lars Feuerbach
    • , J. Lynn Fink
    • , Milana Frenkel-Morgenstern
    • , Dale W. Garsed
    • , Mark Gerstein
    • , Dmitry A. Gordenin
    • , David Haan
    • , James E. Haber
    • , Julian M. Hess
    • , Barbara Hutter
    • , Marcin Imielinski
    • , David T. W. Jones
    • , Young Seok Ju
    • , Marat D. Kazanov
    • , Leszek J. Klimczak
    • , Youngil Koh
    • , Jan O. Korbel
    • , Kiran Kumar
    • , Eunjung Alice Lee
    • , Jake June-Koo Lee
    • , Yilong Li
    • , Andy G. Lynch
    • , Geoff Macintyre
    • , Florian Markowetz
    • , Iñigo Martincorena
    • , Alexander Martinez-Fundichely
    • , Matthew Meyerson
    • , Satoru Miyano
    • , Hidewaki Nakagawa
    • , Fabio C. P. Navarro
    • , Stephan Ossowski
    • , Peter J. Park
    • , John V. Pearson
    • , Montserrat Puiggròs
    • , Karsten Rippe
    • , Nicola D. Roberts
    • , Steven A. Roberts
    • , Bernardo Rodriguez-Martin
    • , Steven E. Schumacher
    • , Ralph Scully
    • , Mark Shackleton
    • , Nikos Sidiropoulos
    • , Lina Sieverling
    • , Chip Stewart
    • , David Torrents
    • , Jose M. C. Tubio
    • , Izar Villasante
    • , Nicola Waddell
    • , Jeremiah A. Wala
    • , Joachim Weischenfeldt
    • , Lixing Yang
    • , Xiaotong Yao
    • , Sung-Soo Yoon
    • , Jorge Zamora
    • , Cheng-Zhong Zhang
    • , Benedikt Brors
    • , Karsten Rippe
    • , David T. W. Jones
    •  & Lars Feuerbach
  • Article
    | Open Access

    Aberrant alternative splicing has been shown to contribute to the tumorigenic processes. Here, the authors show that MTR4 is overexpressed in hepatocellular carcinoma and has a role in tumorigenesis through the modulation of the splicing of glycolytic genes PKM2 and GLUT1.

    • Lili Yu
    • , Jinchul Kim
    • , Lei Jiang
    • , Bingbing Feng
    • , Yue Ying
    • , Kai-yuan Ji
    • , Qingshuang Tang
    • , Wancheng Chen
    • , Taoyi Mai
    • , Wenlong Dou
    • , Jianlong Zhou
    • , Le-yang Xiang
    • , Yang-fan He
    • , Dinghua Yang
    • , Qingjiao Li
    • , Xuemei Fu
    •  & Yang Xu
  • Article
    | Open Access

    Here, using electrical stimulation on patients undergoing awake brain surgery, the authors show that disruption of the premotor cortex makes patients unconscious of motor arrest. This finding suggests the premotor cortex is crucial for motor awareness.

    • Luca Fornia
    • , Guglielmo Puglisi
    • , Antonella Leonetti
    • , Lorenzo Bello
    • , Anna Berti
    • , Gabriella Cerri
    •  & Francesca Garbarini
  • Article
    | Open Access

    The effects of anesthetics on cancer metastasis are largely unknown. Here, the authors show in two preclinical mouse models that surgical resection of primary tumours under anesthesia with sevoflurane leads to more lung metastases than with propofol and that such distinct effects are associated with change of cytokines and modulation of myeloid cells in the lung.

    • Ru Li
    • , Yujie Huang
    •  & Jun Lin
  • Article
    | Open Access

    Relevant features of T cell repertoire in human cancer remain to be delineated. Here the authors show, by TCR sequencing in a large cohort of lung cancer patients, that while a majority of T cell clones are shared between tumor and adjacent lung tissue, less frequent tumor-unique T cell clones correlate with worse prognosis.

    • Alexandre Reuben
    • , Jiexin Zhang
    • , Shin-Heng Chiou
    • , Rachel M. Gittelman
    • , Jun Li
    • , Won-Chul Lee
    • , Junya Fujimoto
    • , Carmen Behrens
    • , Xiaoke Liu
    • , Feng Wang
    • , Kelly Quek
    • , Chunlin Wang
    • , Farrah Kheradmand
    • , Runzhe Chen
    • , Chi-Wan Chow
    • , Heather Lin
    • , Chantale Bernatchez
    • , Ali Jalali
    • , Xin Hu
    • , Chang-Jiun Wu
    • , Agda Karina Eterovic
    • , Edwin Roger Parra
    • , Erik Yusko
    • , Ryan Emerson
    • , Sharon Benzeno
    • , Marissa Vignali
    • , Xifeng Wu
    • , Yuanqing Ye
    • , Latasha D. Little
    • , Curtis Gumbs
    • , Xizeng Mao
    • , Xingzhi Song
    • , Samantha Tippen
    • , Rebecca L. Thornton
    • , Tina Cascone
    • , Alexandra Snyder
    • , Jennifer A. Wargo
    • , Roy Herbst
    • , Stephen Swisher
    • , Humam Kadara
    • , Cesar Moran
    • , Neda Kalhor
    • , Jianhua Zhang
    • , Paul Scheet
    • , Ara A. Vaporciyan
    • , Boris Sepesi
    • , Don L. Gibbons
    • , Harlan Robins
    • , Patrick Hwu
    • , John V. Heymach
    • , Padmanee Sharma
    • , James P. Allison
    • , Veera Baladandayuthapani
    • , Jack J. Lee
    • , Mark M. Davis
    • , Ignacio I. Wistuba
    • , P. Andrew Futreal
    •  & Jianjun Zhang
  • Article
    | Open Access

    Ibrutinib, a Bruton tyrosine kinase inhibitor, provides effective treatment for chronic lymphocytic leukemia (CLL). Here, the authors describe time-dependent molecular changes to malignant cells and to the immune system in patients undergoing ibrutinib therapy, with can be used for therapy monitoring.

    • André F. Rendeiro
    • , Thomas Krausgruber
    • , Nikolaus Fortelny
    • , Fangwen Zhao
    • , Thomas Penz
    • , Matthias Farlik
    • , Linda C. Schuster
    • , Amelie Nemc
    • , Szabolcs Tasnády
    • , Marienn Réti
    • , Zoltán Mátrai
    • , Donát Alpár
    • , Csaba Bödör
    • , Christian Schmidl
    •  & Christoph Bock
  • Article
    | Open Access

    Group 3 medulloblastoma (MB) is considered one of the most aggressive forms of this cancer. Here, the authors show that Otx2 and c-MYC oncogenes can drive Group 3 MB formation in mouse and human cerebellar organoids while SMARCA4 overexpression or a EZH2-specific inhibitor can inhibit tumorigenesis.

    • Claudio Ballabio
    • , Marica Anderle
    • , Matteo Gianesello
    • , Chiara Lago
    • , Evelina Miele
    • , Marina Cardano
    • , Giuseppe Aiello
    • , Silvano Piazza
    • , Davide Caron
    • , Francesca Gianno
    • , Andrea Ciolfi
    • , Lucia Pedace
    • , Angela Mastronuzzi
    • , Marco Tartaglia
    • , Franco Locatelli
    • , Elisabetta Ferretti
    • , Felice Giangaspero
    •  & Luca Tiberi
  • Article
    | Open Access

    Identifying patients that will respond to a particular therapy remains a key challenge in precision oncology. Here, in gastric cancer, the authors show that circulating tumour DNA can predict recurrence, provided that the signal from white blood cells is filtered out.

    • Alessandro Leal
    • , Nicole C. T. van Grieken
    • , Doreen N. Palsgrove
    • , Jillian Phallen
    • , Jamie E. Medina
    • , Carolyn Hruban
    • , Mark A. M. Broeckaert
    • , Valsamo Anagnostou
    • , Vilmos Adleff
    • , Daniel C. Bruhm
    • , Jenna V. Canzoniero
    • , Jacob Fiksel
    • , Marianne Nordsmark
    • , Fabienne A. R. M. Warmerdam
    • , Henk M. W. Verheul
    • , Dick Johan van Spronsen
    • , Laurens V. Beerepoot
    • , Maud M. Geenen
    • , Johanneke E. A. Portielje
    • , Edwin P. M. Jansen
    • , Johanna van Sandick
    • , Elma Meershoek-Klein Kranenbarg
    • , Hanneke W. M. van Laarhoven
    • , Donald L. van der Peet
    • , Cornelis J. H. van de Velde
    • , Marcel Verheij
    • , Remond Fijneman
    • , Robert B. Scharpf
    • , Gerrit A. Meijer
    • , Annemieke Cats
    •  & Victor E. Velculescu
  • Article
    | Open Access

    Experimental PVSRIPO oncolytic virus therapy of glioblastoma has shown long-term efficacy in a subset of patients. Here the authors engineer the virus to enable incorporation of tumor-specific antigens, and show proof-of-principle evidence that this modification increases anti-tumor immunity and extends survival in mice.

    • Mubeen M. Mosaheb
    • , Elena Y. Dobrikova
    • , Michael C. Brown
    • , Yuanfan Yang
    • , Jana Cable
    • , Hideho Okada
    • , Smita K. Nair
    • , Darell D. Bigner
    • , David M. Ashley
    •  & Matthias Gromeier
  • Article
    | Open Access

    Our understanding on how CAFs can be activated to support tumour progression is still limited. Here, the authors demonstrate that adenosine produced in the tumour microenvironment can enhance the expression of CD73 in CAFs ultimately driving CD8 T-Cell suppression and tumour growth.

    • Miao Yu
    • , Gang Guo
    • , Lei Huang
    • , Libin Deng
    • , Chang-Sheng Chang
    • , Bhagelu R. Achyut
    • , Madison Canning
    • , Ningchun Xu
    • , Ali S. Arbab
    • , Roni J. Bollag
    • , Paulo C. Rodriguez
    • , Andrew L. Mellor
    • , Huidong Shi
    • , David H. Munn
    •  & Yan Cui
  • Article
    | Open Access

    Glutamine is an energetic source required for the proliferation of cancer cells. Here, the authors show that soft tissue sarcomas expressing high levels of glutaminase (GLS) are particularly sensitive to glutamine starvation and GLS inhibition in tumour-bearing allograft and autochthonous mouse models.

    • Pearl Lee
    • , Dania Malik
    • , Nicholas Perkons
    • , Peiwei Huangyang
    • , Sanika Khare
    • , Seth Rhoades
    • , Yao-Yu Gong
    • , Michelle Burrows
    • , Jennifer M. Finan
    • , Itzhak Nissim
    • , Terence P. F. Gade
    • , Aalim M. Weljie
    •  & M. Celeste Simon
  • Article
    | Open Access

    The tumour microenvironment is known to have an acidic pH but how this influences cancer cell phenotype is unclear. Here, the authors show that tumour cells upregulate TGF-β2 under acidosis, which leads to the increased formation of lipid droplets allowing for invasiveness and metastases.

    • Cyril Corbet
    • , Estelle Bastien
    • , Joao Pedro Santiago de Jesus
    • , Emeline Dierge
    • , Ruben Martherus
    • , Catherine Vander Linden
    • , Bastien Doix
    • , Charline Degavre
    • , Céline Guilbaud
    • , Laurenne Petit
    • , Carine Michiels
    • , Chantal Dessy
    • , Yvan Larondelle
    •  & Olivier Feron
  • Article
    | Open Access

    There are many patients who do not respond to immune checkpoint inhibitor (ICI) immunotherapy. Here, the authors show a significant negative correlation between sphingosine kinase-1 (SK1) expression and survival for ICI-treated melanoma patients, and further show that targeting SK1 improves response to ICI in mouse cancer models.

    • Caroline Imbert
    • , Anne Montfort
    • , Marine Fraisse
    • , Elie Marcheteau
    • , Julia Gilhodes
    • , Elodie Martin
    • , Florie Bertrand
    • , Marlène Marcellin
    • , Odile Burlet-Schiltz
    • , Anne Gonzalez de Peredo
    • , Virginie Garcia
    • , Stéphane Carpentier
    • , Sophie Tartare-Deckert
    • , Pierre Brousset
    • , Philippe Rochaix
    • , Florent Puisset
    • , Thomas Filleron
    • , Nicolas Meyer
    • , Laurence Lamant
    • , Thierry Levade
    • , Bruno Ségui
    • , Nathalie Andrieu-Abadie
    •  & Céline Colacios