Featured
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Review Article |
Li-Fraumeni syndrome: cancer risk assessment and clinical management
Individuals with Li-Fraumeni syndrome, who carry germline mutations in theTP53 gene that encodes the tumour-suppressor protein p53, are at high risk of developing cancers in multiple organs. In this Review, considerations for cancer screening and management in carriers of TP53mutations are discussed, and an evidence-based approach to cancer surveillance in such individuals is proposed.
- Kate A. McBride
- , Mandy L. Ballinger
- & Gillian Mitchell
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News & Views |
CALR mutations and a new diagnostic algorithm for MPN
Between 2005 and 2007, mutations in JAK2 and MPL were described in most patients with myeloproliferative neoplasms (MPN). These seminal discoveries have forever changed our diagnostic approach to MPN. In December 2013, mutations in CALR were reported in MPN wild-type for JAK2 and MPL. These mutations provide additional diagnostic and prognostic tools in MPN.
- Ayalew Tefferi
- & Animesh Pardanani
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Research Highlight |
Is now the time to extend biomarker stratification to other RAS-family genes?
- Mina Razzak
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Review Article |
Gastric cancer—molecular and clinical dimensions
Momentum is building for carrying out more phase III comparative trials in gastric cancer, with some using biomarker-based patient selection strategies. In this Review, the authors discuss representative molecular and clinical dimensions of gastric cancer, the fourth most common cancer in men and fifth most common cancer in women.
- Roopma Wadhwa
- , Shumei Song
- & Jaffer A. Ajani
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Review Article |
Liquid biopsy: monitoring cancer-genetics in the blood
As heterogeneity increasingly needs to be taken into account in the treatment of solid tumours, methods to detect genetic variation have come to the fore. One method that might have considerable clinical utility is the detection of variations in circulating-free DNA. This Review outlines the possibilities and challenges that this technique offers in terms of predictive and prognostic markers, as well as in the detection of therapy resistance.
- Emily Crowley
- , Federica Di Nicolantonio
- & Alberto Bardelli
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Review Article |
Paradoxical oncogenesis—the long-term effects of BRAF inhibition in melanoma
Although patients with melanoma generally benefit from BRAF or MEK targeted therapies, adverse events can occur on treatment, including the emergence of second malignancies. Evidence suggests unintended or paradoxical activation of MAPK signalling might underlie the majority of these second malignancies. The authors discuss the basis for this paradoxical MAPK activation, and the rationale for novel therapeutic strategies for the management of BRAF-inhibitor-induced neoplasia.
- Geoffrey T. Gibney
- , Jane L. Messina
- & Keiran S. M. Smalley
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Review Article |
The future of epigenetic therapy in solid tumours—lessons from the past
Describing data from preclinical studies and early clinical trial results, Azad et al. suggest that low-dose epigenetic-modulating agents can reprogramme tumour cells and override any immediate cytotoxic effects that are typically observed at high doses. Such optimization of drug dosing and scheduling of currently available epigenetic therapies could give these agents a prominent place in cancer management—when used alone or in combination with other therapies.
- Nilofer Azad
- , Cynthia A. Zahnow
- & Stephen B. Baylin
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Review Article |
Aetiology, genetics and prevention of secondary neoplasms in adult cancer survivors
The occurrence of second malignant neoplasms in survivors of cancer is one of the most serious complications of cancer and its treatment. Second and higher-order malignancies now comprise about 18% of all incident cancers in the USA, superseding first primary cancers of the breast, lung, and prostate. This Review article discusses the wide-range of factors that influence the occurrence of second malignant neoplasms and a review of modifiable behavioural and lifestyle factors.
- Lois B. Travis
- , Wendy Demark Wahnefried
- & Andrea K. Ng
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In Brief |
New disease entity identified for meningioma
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Review Article |
Clinical opportunities and challenges in targeting tumour dormancy
Tumour dormancy is when cancer sleeps undetected for periods that can last up to decades. The therapeutic potential of inducing or maintaining this dormant period is clear. This Review describes the mechanisms of dormancy and uses genitourinary cancers as models to demonstrate how dormancy principles could be exploited clinically.
- Jonathan A. Hensel
- , Thomas W. Flaig
- & Dan Theodorescu
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Research Highlight |
11q negative neuroblastoma subgroups predict outcomes and may guide treatment
- Rebecca Kirk
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News & Views |
HPV testing for cervical cancer: the good, the bad, and the ugly
A randomized, controlled trial has shown human papillomavirus (HPV) DNA testing with and without liquid-based cytology to be more sensitive but less specific than conventional Papanicolaou smears for detection of precancerous lesions of the cervix. The lead-time advantage of early detection of precancerous lesions by HPV DNA testing resulted in cervical cancer reduction; however, an increased detection of possibly regressive precancerous lesions could result in unnecessary treatment, especially in women aged 25–34 years.
- Philip E. Castle
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Review Article |
Molecular markers to individualize adjuvant therapy for colon cancer
Prognostic and predictive markers in colon cancer might help define which patients with stage II disease are likely to benefit from adjuvant therapy. In this Review, Tara Gangadhar and Richard Schilsky discuss the recent clinical development of such markers, including microsatellite instability and 18q loss of heterozygosity. Further validation of these markers could potentially lead to the individualization of adjuvant therapy in colon cancer.
- Tara Gangadhar
- & Richard L. Schilsky