Editorial |
Featured Content
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Article |
Trispecific antibodies enhance the therapeutic efficacy of tumor-directed T cells through T cell receptor co-stimulation
Wu et al. develop trispecific antibodies that recognize CD38, CD3 and CD28 and induce T cell activation and co-signaling. They show in mice and non-human primates that by engaging multiple targets, these antibodies induce enhanced tumor-cell killing.
- Lan Wu
- , Edward Seung
- , Ling Xu
- , Ercole Rao
- , Dana M. Lord
- , Ronnie R. Wei
- , Virna Cortez-Retamozo
- , Beatriz Ospina
- , Valeriya Posternak
- , Gregory Ulinski
- , Peter Piepenhagen
- , Elisa Francesconi
- , Nizar El-Murr
- , Christian Beil
- , Patrick Kirby
- , Aiqun Li
- , Jennifer Fretland
- , Rita Vicente
- , Gejing Deng
- , Tarik Dabdoubi
- , Beatrice Cameron
- , Thomas Bertrand
- , Paul Ferrari
- , Stéphanie Pouzieux
- , Cendrine Lemoine
- , Catherine Prades
- , Anna Park
- , Huawei Qiu
- , Zhili Song
- , Bailin Zhang
- , Fangxian Sun
- , Marielle Chiron
- , Srinivas Rao
- , Katarina Radošević
- , Zhi-yong Yang
- & Gary J. Nabel
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Article |
A unifying paradigm for transcriptional heterogeneity and squamous features in pancreatic ductal adenocarcinoma
Iacobuzio-Donahue and colleagues use integrated transcriptomic, histologic and mutational data to analyze squamous features of pancreatic ductal adenocarcinoma (PDAC), further refining the understanding of heterogeneity and evolution in PDAC.
- Akimasa Hayashi
- , Jun Fan
- , Ruoyao Chen
- , Yu-jui Ho
- , Alvin P. Makohon-Moore
- , Nicolas Lecomte
- , Yi Zhong
- , Jungeui Hong
- , Jinlong Huang
- , Hitomi Sakamoto
- , Marc A. Attiyeh
- , Zachary A. Kohutek
- , Lance Zhang
- , Aida Boumiza
- , Rajya Kappagantula
- , Priscilla Baez
- , Jessica Bai
- , Marta Lisi
- , Kalyani Chadalavada
- , Jerry P. Melchor
- , Winston Wong
- , Gouri J. Nanjangud
- , Olca Basturk
- , Eileen M. O’Reilly
- , David S. Klimstra
- , Ralph H. Hruban
- , Laura D. Wood
- , Michael Overholtzer
- & Christine A. Iacobuzio-Donahue
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Resource |
Discovering the anticancer potential of non-oncology drugs by systematic viability profiling
Golub and colleagues tested thousands of drugs not originally developed for oncology across 578 human cancer cell lines, revealing growth-inhibitory effects and providing a resource to identify drugs with the potential to be repurposed for cancer.
- Steven M. Corsello
- , Rohith T. Nagari
- , Ryan D. Spangler
- , Jordan Rossen
- , Mustafa Kocak
- , Jordan G. Bryan
- , Ranad Humeidi
- , David Peck
- , Xiaoyun Wu
- , Andrew A. Tang
- , Vickie M. Wang
- , Samantha A. Bender
- , Evan Lemire
- , Rajiv Narayan
- , Philip Montgomery
- , Uri Ben-David
- , Colin W. Garvie
- , Yejia Chen
- , Matthew G. Rees
- , Nicholas J. Lyons
- , James M. McFarland
- , Bang T. Wong
- , Li Wang
- , Nancy Dumont
- , Patrick J. O’Hearn
- , Eric Stefan
- , John G. Doench
- , Caitlin N. Harrington
- , Heidi Greulich
- , Matthew Meyerson
- , Francisca Vazquez
- , Aravind Subramanian
- , Jennifer A. Roth
- , Joshua A. Bittker
- , Jesse S. Boehm
- , Christopher C. Mader
- , Aviad Tsherniak
- & Todd R. Golub
Latest Research
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Article |
Circulating tumor DNA dynamics predict benefit from consolidation immunotherapy in locally advanced non-small-cell lung cancer
Diehn and colleagues report that assaying circulating DNA in patients receiving chemoradiation therapy for non-small-cell lung cancer could identify the patients most likely to benefit from consolidation immunotherapy.
- Everett J. Moding
- , Yufei Liu
- , Barzin Y. Nabet
- , Jacob J. Chabon
- , Aadel A. Chaudhuri
- , Angela B. Hui
- , Rene F. Bonilla
- , Ryan B. Ko
- , Christopher H. Yoo
- , Linda Gojenola
- , Carol D. Jones
- , Jianzhong He
- , Yawei Qiao
- , Ting Xu
- , John V. Heymach
- , Anne Tsao
- , Zhongxing Liao
- , Daniel R. Gomez
- , Millie Das
- , Sukhmani K. Padda
- , Kavitha J. Ramchandran
- , Joel W. Neal
- , Heather A. Wakelee
- , Billy W. Loo Jr
- , Steven H. Lin
- , Ash A. Alizadeh
- & Maximilian Diehn
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Article |
MTSS1 suppresses mammary tumor-initiating cells by enhancing RBCK1-mediated p65 ubiquitination
Cong et al. show that MTSS1 suppresses breast cancer initiation by promoting ubiquitin-mediated suppression of the NF-κB pathway. Loss of this regulatory mechanism promotes the activation and expansion of tumor-initiating cells.
- Min Cong
- , Yuan Wang
- , Yang Yang
- , Cheng Lian
- , Xueqian Zhuang
- , Xiaoxun Li
- , Peiyuan Zhang
- , Yingjie Liu
- , Jun Tang
- , Qifeng Yang
- , Xue Zhang
- , Hua Xiong
- , Ronggui Hu
- & Guohong Hu
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Resource |
Discovering the anticancer potential of non-oncology drugs by systematic viability profiling
Golub and colleagues tested thousands of drugs not originally developed for oncology across 578 human cancer cell lines, revealing growth-inhibitory effects and providing a resource to identify drugs with the potential to be repurposed for cancer.
- Steven M. Corsello
- , Rohith T. Nagari
- , Ryan D. Spangler
- , Jordan Rossen
- , Mustafa Kocak
- , Jordan G. Bryan
- , Ranad Humeidi
- , David Peck
- , Xiaoyun Wu
- , Andrew A. Tang
- , Vickie M. Wang
- , Samantha A. Bender
- , Evan Lemire
- , Rajiv Narayan
- , Philip Montgomery
- , Uri Ben-David
- , Colin W. Garvie
- , Yejia Chen
- , Matthew G. Rees
- , Nicholas J. Lyons
- , James M. McFarland
- , Bang T. Wong
- , Li Wang
- , Nancy Dumont
- , Patrick J. O’Hearn
- , Eric Stefan
- , John G. Doench
- , Caitlin N. Harrington
- , Heidi Greulich
- , Matthew Meyerson
- , Francisca Vazquez
- , Aravind Subramanian
- , Jennifer A. Roth
- , Joshua A. Bittker
- , Jesse S. Boehm
- , Christopher C. Mader
- , Aviad Tsherniak
- & Todd R. Golub
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Article |
Molecular analysis of primary melanoma T cells identifies patients at risk for metastatic recurrence
Kupper and colleagues introduce the T-cell fraction as a molecular assessment of T-cell-mediated antitumor responses in primary melanomas that can predict metastatic recurrence.
- Wiebke Pruessmann
- , Julie Rytlewski
- , James Wilmott
- , Martin C. Mihm Jr
- , Grace H. Attrill
- , Beatrice Dyring-Andersen
- , Paul Fields
- , Qian Zhan
- , Andrew J. Colebatch
- , Peter M. Ferguson
- , John F. Thompson
- , Klaus Kallenbach
- , Erik Yusko
- , Rachael A. Clark
- , Harlan Robins
- , Richard A. Scolyer
- & Thomas S. Kupper
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Article |
Multimodal genomic features predict outcome of immune checkpoint blockade in non-small-cell lung cancer
Anagnostou et al. present an improved predictor of response to immune checkpoint blockade that integrates estimates of tumor mutational burden corrected for tumor purity, RTK genomic alterations, a smoking-related mutational signature and HLA status.
- Valsamo Anagnostou
- , Noushin Niknafs
- , Kristen Marrone
- , Daniel C. Bruhm
- , James R. White
- , Jarushka Naidoo
- , Karlijn Hummelink
- , Kim Monkhorst
- , Ferry Lalezari
- , Mara Lanis
- , Samuel Rosner
- , Joshua E. Reuss
- , Kellie N. Smith
- , Vilmos Adleff
- , Kristen Rodgers
- , Zineb Belcaid
- , Lamia Rhymee
- , Benjamin Levy
- , Josephine Feliciano
- , Christine L. Hann
- , David S. Ettinger
- , Christos Georgiades
- , Franco Verde
- , Peter Illei
- , Qing Kay Li
- , Alexander S. Baras
- , Edward Gabrielson
- , Malcolm V. Brock
- , Rachel Karchin
- , Drew M. Pardoll
- , Stephen B. Baylin
- , Julie R. Brahmer
- , Robert B. Scharpf
- , Patrick M. Forde
- & Victor E. Velculescu
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Article |
Higher prevalence of homologous recombination deficiency in tumors from African Americans versus European Americans
Ryan and colleagues analyze genomic features in tumors from African Americans and European Americans and find that homologous recombination deficiency is more prevalent in African Americans.
- Sanju Sinha
- , Khadijah A. Mitchell
- , Adriana Zingone
- , Elise Bowman
- , Neelam Sinha
- , Alejandro A. Schäffer
- , Joo Sang Lee
- , Eytan Ruppin
- & Bríd M. Ryan
News & Comment
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News & Views |
Old drugs with new tricks
Drug repurposing is an attractive strategy for extending the arsenal of oncology therapies. Screening of a large collection of existing non-oncology compounds against a panel of cancer cell lines now identifies several drugs capable of selectively inhibiting the growth of cancer cells.
- Roderick L. Beijersbergen
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Comment |
Securing the future of the clinician-scientist
By integrating discovery science with clinical practice and therapeutic intervention, clinician-scientists fulfil a unique role in cancer research. However, their numbers are in decline, which is creating the need for flexible training and research opportunities to ensure their future.
- Karen Noble
- , Joanna Owens
- , Fabrice André
- , Samuel F. Bakhoum
- , Sherene Loi
- , Hans Christian Reinhardt
- , David Tuveson
- & Charles Swanton
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News & Views |
Finding cancer drivers in the UPS system
Identifying cancer driver mutations is essential to understand disease biology and devise effective therapies, but remains a complex endeavor. A focused analytical approach is now presented that defines driver mutations affecting ubiquitin-mediated proteolysis through machine learning and mining of cancer multi-omics data.
- Han Liang
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Q&A |
Shaping the future of cancer research at NCI
Norman E. ‘Ned’ Sharpless became director of the US National Cancer Institute (NCI) in 2017. From April 2019, he served as acting commissioner of the US Food and Drug Administration (FDA), and he returned to the NCI in November. Douglas R. Lowy has been the principal deputy director of the NCI since 2010, having also served as acting director twice, most recently in 2019. Nature Cancer spoke with both last fall to learn more about what makes NCI and its leadership tick.
- Alexia-Ileana Zaromytidou
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Comment |
Intratumor heterogeneity reflects clinical disease course
Intratumoral genetic heterogeneity of driver somatic mutations is present in a variety of tumor types, yet the extent of heterogeneity is variable. We propose that this variation is a reflection of the inherent biology of a given tumor type, representing the pace of metastatic dissemination and hence clinical disease course.
- Christine A. Iacobuzio-Donahue
- , Kevin Litchfield
- & Charles Swanton
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Viewpoint |
A roadmap for the next decade in cancer research
Cancer research in recent years has been marked by significant developments in understanding disease biology and foundational discoveries that have changed clinical practice. Ten cancer researchers take stock of the field, the advances that excite them, key outstanding questions and breakthroughs they anticipate looking forward.
- René Bernards
- , Elizabeth Jaffee
- , Johanna A. Joyce
- , Scott W. Lowe
- , Elaine R. Mardis
- , Sean J. Morrison
- , Kornelia Polyak
- , Cynthia L. Sears
- , Karen H. Vousden
- & Zemin Zhang
Trispecific antibodies enhance the therapeutic efficacy of tumor-directed T cells through T cell receptor co-stimulation
A unifying paradigm for transcriptional heterogeneity and squamous features in pancreatic ductal adenocarcinoma
Discovering the anticancer potential of non-oncology drugs by systematic viability profiling
Circulating tumor DNA dynamics predict benefit from consolidation immunotherapy in locally advanced non-small-cell lung cancer
MTSS1 suppresses mammary tumor-initiating cells by enhancing RBCK1-mediated p65 ubiquitination
Molecular analysis of primary melanoma T cells identifies patients at risk for metastatic recurrence
Multimodal genomic features predict outcome of immune checkpoint blockade in non-small-cell lung cancer
Higher prevalence of homologous recombination deficiency in tumors from African Americans versus European Americans
Old drugs with new tricks
Securing the future of the clinician-scientist
Finding cancer drivers in the UPS system
Shaping the future of cancer research at NCI
Intratumor heterogeneity reflects clinical disease course
A roadmap for the next decade in cancer research