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The latest articles published online ahead of print. These online versions are definitive and may be cited using the digital object identifier (DOI).


16 May 2017

Research Highlight

Lung cancer: Tracing tumour evolution | PDF (127 KB)

Published online: 16 May 2017 | doi:10.1038/nrclinonc.2017.73




Early phase clinical trials of anticancer agents in children and adolescents — an ITCC perspective

Lucas Moreno, Andrew D. J. Pearson, Xavier Paoletti, Irene Jimenez, Birgit Geoerger, Pamela R. Kearns, C. Michel Zwaan, Francois Doz, Andre Baruchel, Josef Vormoor, Michela Casanova, Stefan M. Pfister, Bruce Morland, Gilles Vassal & on behalf of the Innovative Therapies for Children with Cancer (ITCC) Consortium

Published online: 16 May 2017 | doi:10.1038/nrclinonc.2017.59

Precision medicine has dramatically changed the landscape of drug development in oncology, but this paradigm shift remains to be adopted in early phase clinical trials of molecularly targeted agents and immunotherapeutic agents in children with cancer. The authors, members of the Innovative Therapies for Children with Cancer (ITCC) Consortium, describe trial design strategies to enable drugs with promising activity to progress rapidly to randomized studies and, therefore, substantially accelerate drug development for children and adolescents with cancer.


09 May 2017

Research Highlight

Immunotherapy: Nivolumab keeps HCC in check and opens avenues for checkmate | PDF (87 KB)

Published online: 09 May 2017 | doi:10.1038/nrclinonc.2017.70


25 April 2017

News and Views

Immunotherapy: Does adjuvant ipilimumab have little adverse effect on quality of life?

Paul Lorigan & Adele C. Green

Published online: 25 April 2017 | doi:10.1038/nrclinonc.2017.60

Adjuvant ipilimumab is associated with an 11% improvement in 5-year overall survival in patients with high-risk melanoma, but at the cost of considerable toxicity, with half of patients discontinuing treatment owing to adverse events. An analysis of quality-of-life (QoL) outcomes, however, showed little impact of adverse effects of this treatment on QoL, which is puzzling.


11 April 2017

News and Views

Gynaecological cancer: Novel molecular subtypes of cervical cancer — potential clinical consequences

Chris J. L. M. Meijer & Renske D. M. Steenbergen

Published online: 11 April 2017 | doi:10.1038/nrclinonc.2017.52

The Cancer Genome Atlas Research Network recently published the most comprehensive, multi-omic molecular characterization of cervical cancers performed to date. The data reveal novel disease subtypes, and provide new insights into the aetiology and pathogenesis of cervical cancer. Importantly, the information obtained has potentially major clinical implications.



EMT, CSCs, and drug resistance: the mechanistic link and clinical implications

Tsukasa Shibue & Robert A. Weinberg

Published online: 11 April 2017 | doi:10.1038/nrclinonc.2017.44

According to the cancer stem cell (CSC) paradigm, a minor subpopulation of cancer cells with stem-cell properties predominantly underlies tumour progression, therapy resistance, and disease recurrence. Notably, epithelial-to-mesenchymal transition (EMT) is implicated in these processes, and CSCs typically show markers of EMT-programme activation. Herein, the authors outline our current understanding of the links between the EMT programme, the CSC phenotype, metastasis, and drug resistance, and discuss the potential for therapeutic targeting of these facets of tumour biology.


04 April 2017


Targeting c-MET in gastrointestinal tumours: rationale, opportunities and challenges

Conor A. Bradley, Manuel Salto-Tellez, Pierre Laurent-Puig, Alberto Bardelli, Christian Rolfo, Josep Tabernero, Hajrah A. Khawaja, Mark Lawler, Patrick G. Johnston, Sandra Van Schaeybroeck & on behalf of the MErCuRIC consortium

Published online: 04 April 2017 | doi:10.1038/nrclinonc.2017.40

Patients with c-MET-expressing colorectal or gastrointestinal cancers generally have worse outcomes than those of patients whose tumours have low levels of, or absent c-MET expression. However, c-MET targeted agents have, thus far, failed to show clinical efficacy. In this Review, the authors describe the opportunities and challenges created by the clinical implementation of c-MET targeted therapies.

Targeted agents and immunotherapies: optimizing outcomes in melanoma

Jason J. Luke, Keith T. Flaherty, Antoni Ribas & Georgina V. Long

Published online: 04 April 2017 | doi:10.1038/nrclinonc.2017.43

In less than a decade, the treatment landscape of metastatic melanoma has changed dramatically. Novel targeted agents and immunotherapies are revolutionizing patient outcomes, but the range of available drugs complicates clinical decision-making. Herein, the authors chart the therapeutic advances and review the current evidence that can be used to guide therapeutic decisions for individual patients with metastatic melanoma, highlighting knowledge gaps.


14 March 2017


Charged-particle therapy in cancer: clinical uses and future perspectives

Marco Durante, Roberto Orecchia & Jay S. Loeffler

Published online: 14 March 2017 | doi:10.1038/nrclinonc.2017.30

Conventional radiotherapy with X-rays is being replaced by radiotherapy with high-energy charged particles, an approach that better spares healthy tissue from radiation but is associated with higher costs. Evidence supporting the cost-effectiveness of either modality can only come from the results of randomized clinical trials. The authors of this Review discuss ongoing randomized trials of charged-particle therapies as well as aspects related to radiobiology, which need to be taken into account in order to fully exploit the therapeutic potential of charged particles.


02 March 2017


Integrating liquid biopsies into the management of cancer

Giulia Siravegna, Silvia Marsoni, Salvatore Siena & Alberto Bardelli

Published online: 02 March 2017 | doi:10.1038/nrclinonc.2017.14

Analysis of circulating tumour components using liquid biopsy approaches holds considerable promise to improve the detection and treatment of cancer. In this Review, Alberto Bardelli and colleagues outline how different forms of liquid biopsy, and particularly the assessment of circulating tumour DNA, can be exploited to guide patient care, and discuss the progress made to date in integrating such analyses into the clinic.


14 February 2017



The changing landscape of clinical trial and approval processes in China

Qing Zhou, Xiao-Yuan Chen, Zhi-Min Yang & Yi-Long Wu

Published online: 14 February 2017 | doi:10.1038/nrclinonc.2017.10

The expansion of research and development of anticancer drugs in China has resulted in considerable delays in the approval of both clinical trials of novel agents, and the marketing approval of these agents once tested. In this Perspective, the authors describe the measures taken by the Chinese FDA to address these challenges in a rapidly developing research environment.


24 January 2017


Proteasome inhibitors in cancer therapy

Elisabet E. Manasanch & Robert Z. Orlowski

Published online: 24 January 2017 | doi:10.1038/nrclinonc.2016.206

By preventing the accumulation of misfolded or damaged proteins, the ubiquitin-proteasome pathway has essential functions in cell homeostasis. Cancer cells produce proteins that promote cell survival and proliferation, and inhibit cell death, and thus, clinical trials have tested the therapeutic effect of proteasome inhibitors on patients with a variety of cancer types, mainly haematological malignancies. Herein, the authors discuss the advances and challenges derived from the introduction of proteasome inhibitors in the clinic, including therapeutic resistance.

Tumour-associated macrophages as treatment targets in oncology

Alberto Mantovani, Federica Marchesi, Alberto Malesci, Luigi Laghi & Paola Allavena

Published online: 24 January 2017 | doi:10.1038/nrclinonc.2016.217

Tumour-associated macrophages (TAMs) are key drivers of tumour-promoting inflammation and cancer progression, and are important determinants of responsiveness to a range of therapies. Herein, the authors summarize the roles of TAMs in cancer, and discuss the potential of TAM-targeted therapeutic strategies to complement and synergize with other anticancer treatments.


29 December 2016


Advances in the molecular genetics of gliomas — implications for classification and therapy

Guido Reifenberger, Hans-Georg Wirsching, Christiane B. Knobbe-Thomsen & Michael Weller

Published online: 29 December 2016 | doi:10.1038/nrclinonc.2016.204

In 2016, a revised WHO classification of glioma was published, in which molecular data and traditional histological information are incorporated into integrated diagnoses. Herein, the authors highlight the developments in our understanding of the molecular genetics of gliomas that underlie this classification, and review the current landscape of molecular biomarkers used in the classification of disease subtypes. In addition, they discuss how these advances can promote the development of novel pathogenesis-based therapeutic approaches, paving the way to precision medicine.


29 November 2016



The need for multidisciplinarity in specialist training to optimize future patient care

Alison C. Tree, Victoria Harding, Aneel Bhangu, Venkatesh Krishnasamy, Dion Morton, Justin Stebbing, Bradford J. Wood & Ricky A. Sharma

Published online: 29 November 2016 | doi:10.1038/nrclinonc.2016.185

A multidisciplinary approach is essential for the optimization of patient care in oncology, especially in the current landscape, in which standard-of-care approaches to cancer treatment are evolving towards highly targeted treatments, precise image guidance and personalized cancer therapy. Herein, the authors discuss current career development pathways for oncologists, suggesting strategies to improve clinical training and research, with specific emphasis on the involvement of trainees in multidisciplinary teams.


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Until print versions of AOP papers are published, they should be cited in the style "Nature Reviews Clinical Oncology AOP, published online day month year; doi:10.1038/nrclinoncXXX". Once the print version (identical to the AOP) is published, it should be cited as follows: "Nature Reviews Clinical Oncology volume number, page range (year); doi:10.1038/nrclinoncXXX".

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