Research Highlight |
Featured
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Review Article |
Towards a new classification of gastroenteropancreatic neuroendocrine neoplasms
Contrary to other cancer types, histopathology remains the mainstay of diagnosis and classification of gastroenteropancreatic neuroendocrine neoplasms (GEP-NENs). Increasing knowledge of the molecular genetics and biology of GEP-NENs promises to improve classification of disease subtypes, and thus the management of the disease. Herein, the authors discuss the features of GEP-NENs that, as prognostic or predictive biomarkers, could form the basis for a novel, clinically useful molecular classification system.
- Mark Kidd
- , Irvin Modlin
- & Kjell Öberg
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Review Article |
Cancer metabolism: a therapeutic perspective
Metabolic reprogramming to support tumour growth is a near universal characteristic of cancer, and thus targeting cancer metabolism has been, and continues to be, a focus for drug-development efforts. In this Review, the authors describe the various metabolic alterations and vulnerabilities of tumours that are potentially important targets for anticancer agents, highlighting both the challenges and opportunities.
- Ubaldo E. Martinez-Outschoorn
- , Maria Peiris-Pagés
- & Michael P. Lisanti
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Review Article |
Diet, nutrition, and cancer: past, present and future
Diet has long been linked with the development and progression of cancer, and indeed obesity is a clear risk factor for many cancers; however, teasing out the relationships between nutritional factors and cancer aetiology has proved difficult, complicating the development of dietary recommendations for cancer prevention. In this Review, the issues and challenges in diet–cancer research are discussed, including those relating to the design of epidemiological studies, dietary data collection methods, and factors that affect the outcome of intervention trials.
- Susan T. Mayne
- , Mary C. Playdon
- & Cheryl L. Rock
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Review Article |
Molecular therapy for acute myeloid leukaemia
Acute myeloid leukaemia (AML) is a heterogeneous disease that is typically associated with a very poor prognosis; however, cytogenetic and molecular abnormalities that characterize different forms of AML have been used to better prognosticate patients and inform treatment strategies, which might enable better outcomes to be achieved. Moreover, in the era of next-generation sequencing and molecularly targeted therapy, genetic profiling of patients with AML could open new avenues of treatment. Herein, the authors discuss the evidence-base for integrating mutational data into treatment decisions for patients with AML, and propose novel therapeutic algorithms aimed at improving outcomes of this dismal disease by promoting clinical research.
- Catherine C. Coombs
- , Martin S. Tallman
- & Ross L. Levine
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Research Highlight |
Molecular stratification and repair defects: revealing hidden treasures
- Lisa Hutchinson
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Review Article |
The influence of subclonal resistance mutations on targeted cancer therapy
The molecularly targeted therapy paradigm has led to improvements in the management of patients with cancer. Responses to targeted therapies are, however, mostly short-lived, owing to inherent or acquired resistance, which in most cases relates to the outgrowth of pre-existent rare subclones harbouring resistance mutations. Our current understanding of this concept is reviewed herein; how knowledge of pre-existing resistance mechanism obtained through the use of ultra-sensitive sensitive DNA-sequencing assays might be best exploited to improve personalized medicine is discussed.
- Michael W. Schmitt
- , Lawrence A. Loeb
- & Jesse J. Salk
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Review Article |
Post-transplantation malignancies: here today, gone tomorrow?
The incidence of cancer in transplant recipients is indisputably higher than that of the age-matched general population, and the increased cancer development in transplant recipients who require immunosuppression to avoid graft rejection is well recognized. This Review discusses the advances with mTOR inhibitors that interfere with tumour development via immune and non-immune mechanisms, and the current and future perspectives on how best to normalize the unacceptably high rates of post-transplantation malignancies are highlighted.
- Edward K. Geissler
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Review Article |
Systems biology approaches to adverse drug effects: the example of cardio-oncology
Cardiotoxic effects of chemotherapy can occur in various different ways depending upon the type of chemotherapy used and various patient characteristics. In this Review, the authors describe the established cardiotoxic effects of anthracyclines and HER2 inhibitors, and describe a systems medicine approach that might enable the optimal management of acute and chronic cardiotoxcities in patients who are receiving, or have received, these therapies.
- Sherry-Ann Brown
- , Nicole Sandhu
- & Joerg Herrmann
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News & Views |
What do breast and CRC cancers and MS have in common?
Dairy cattle meat and milk factors are proposed as risks for colon and breast cancers. Several novel small circular DNAs that are genetically active in human cells have been isolated from bovine sera and milk. Such agents have also been detected in two lesions of multiple sclerosis. A unifying concept is presented putatively explaining the risks for these diseases that are associated with these factors.
- Harald zur Hausen
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News & Views |
Management of GIST—go beyond imatinib: treat resistant subtypes
The results of the ENESTg1 trial confirm the efficacy of imatinib, but not nilotinib, as a first-line treatment for gastrointestinal stromal tumours (GISTs) harbouring sensitizing mutations in KIT or PDGFRA. Nilotonib might prove to be beneficial in other subset of patients; however, there remains an urgent unmet need to address the GIST subtypes that are therapeutic orphans.
- Maria A. Pantaleo
- & Guido Biasco
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Review Article |
Advances in targeted therapies for hepatocellular carcinoma in the genomic era
Liver cancer mortality has increased in the past 20 years, and estimates indicate that the global health burden of this disease will continue to grow. Advances in our knowledge of the human genome have provided a comprehensive picture of commonly mutated genes in patients with hepatocellular carcinoma (HCC). In this Review, the authors summarize the molecular concepts of progression of HCC, discuss the potential reasons for clinical trial failure, and propose new concepts of drug development.
- Josep M. Llovet
- , Augusto Villanueva
- & Richard S. Finn
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Opinion |
Mouse hospital and co-clinical trial project—from bench to bedside
Currently, most novel chemotherapies are initially tested in tumour cell lines and xenografts, which generally fail to reflect the full spectrum of tumour-specific mutations, and might explain the low success rates of experimental treatments. In this Perspectives, the mouse hospital co-clinical trial project is described, which enables treatments to be tested in mouse models that accurately reflect the tumour characteristics of individual patients.
- John G. Clohessy
- & Pier Paolo Pandolfi
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Review Article |
Can oncology recapitulate paleontology? Lessons from species extinctions
The evolutionary biology of cancers and organismal species are similar: in both cases, a genetically diverse population mutates and evolves through natural selection. In addition, driving both species and cancers to extinction is extremely difficult. Nevertheless, greater than 99.9% of species that have lived on Earth are now extinct, and the parallels between tumours and organismal evolution suggest that understanding species extinction through paleontology could teach us much about how to eradicate cancers. In this Review, the selective pressures that have driven species extinct and the characteristics of species that make them resistant to extinction are described, and how these factors can be translated to cancers in order to develop improved approaches to therapy and prognosis is discussed.
- Viola Walther
- , Crispin T. Hiley
- & Carlo C. Maley
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Review Article |
Using tumour phylogenetics to identify the roots of metastasis in humans
The routes and timing of metastatic dissemination during cancer progression remain shrouded in mystery. However, phylogenetic studies are beginning to shed new light on this process and various models have been proposed. In this Review, Kamila Naxerova and Rakesh Jain discuss the hypothesized trajectories of metastasis, and examine the extent to which the current phylogenetic evidence support these models. In addition, the experimental techniques of lineage tracing, their strengths and weaknesses, and future directions for studies using such methods are discussed.
- Kamila Naxerova
- & Rakesh K. Jain
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Opinion |
Management of familial cancer: sequencing, surveillance and society
Many cancers, particularly those that arise in childhood, have a hereditary component. In this Perspectives article, the authors provide their views on how the increased adoption of high-throughput DNA sequencing technologies, which produce vast genetic data that is not necessarily limited to known cancer-susceptibility loci, and cancer surveillance strategies are influencing the clinical management of familial cancer. Important ethical issues relating to genetic counselling and disclosure of genetic information on disease susceptibility are discussed, and strategies for approaching these ethical dilemmas are proposed.
- Nardin Samuel
- , Anita Villani
- & David Malkin
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Research Highlight |
Driver genes are mutated early in the course of oesophageal adenocarcinoma
- Natalie J. Wood
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News & Views |
The translocation behind follicular lymphoma development
Healthy individuals carrying the t(14;18) translocation might never develop follicular lymphoma (FL). However, individuals with more than 1 in 10,000 cells carrying this translocation are at high-risk of developing FL. The identification of this high-risk population will help define the pathways driving FL and designing targeted therapies to use before its development.
- Clémentine Sarkozy
- & Bertrand Coiffier
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Review Article |
Sinonasal carcinoma: clinical, pathological, genetic and therapeutic advances
The sinonasal cavities are affected by a range of tumour types, the most common of which are sinonasal squamous-cell carcinoma (SNSCC) and intestinal-type adenocarcinoma (ITAC). Compared with the main types of head and neck cancer, these sinonasal cancers have distinct epidemiological, clinical, aetiological, pathological and genetic characteristics, and require specialized treatment, bearing in mind their important anatomical location. All these aspects of ITAC and SNSCC are reviewed in this article.
- José Luis Llorente
- , Fernando López
- & Mario A. Hermsen
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