Journal ArticleDOI
Implementing personalized cancer genomics in clinical trials
TLDR
Some of the challenges of adapting data for rare cancers or molecular subsets of certain cancers, which will require aligning the availability of investigational agents, rapid turnaround of clinical grade sequencing, molecular eligibility and reconsidering clinical trial design and end points are discussed.Abstract:
The recent surge in high-throughput sequencing of cancer genomes has supported an expanding molecular classification of cancer. These studies have identified putative predictive biomarkers signifying aberrant oncogene pathway activation and may provide a rationale for matching patients with molecularly targeted therapies in clinical trials. Here, we discuss some of the challenges of adapting these data for rare cancers or molecular subsets of certain cancers, which will require aligning the availability of investigational agents, rapid turnaround of clinical grade sequencing, molecular eligibility and reconsidering clinical trial design and end points.read more
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Liquid biopsy: monitoring cancer-genetics in the blood.
TL;DR: This Review will explore how tumour-associated mutations detectable in the blood can be used in the clinic after diagnosis, including the assessment of prognosis, early detection of disease recurrence, and as surrogates for traditional biopsies with the purpose of predicting response to treatments and the development of acquired resistance.
Journal ArticleDOI
Subclonal diversification of primary breast cancer revealed by multiregion sequencing
Lucy R. Yates,Moritz Gerstung,Stian Knappskog,Christine Desmedt,Gunes Gundem,Peter Van Loo,Turid Aas,L. Alexandrov,Denis Larsimont,Helen Davies,Yang Li,Young Seok Ju,Manasa Ramakrishna,Hans Kristian Haugland,Peer Kaare Lilleng,Serena Nik-Zainal,Stuart McLaren,Adam Butler,Sancha Martin,Dominic D Glodzik,Andrew Menzies,Keiran Raine,Jonathan Hinton,David T. Jones,Laura Mudie,Bing B Jiang,Delphine Vincent,April Greene-Colozzi,Pierre-Yves Adnet,Aquila Fatima,Marion Maetens,Michail Ignatiadis,Michael R. Stratton,Christos Sotiriou,Andrea L. Richardson,Per Eystein Lønning,David C. Wedge,Peter J. Campbell +37 more
TL;DR: To understand the subclonal structure of primary breast cancer, whole-genome and targeted sequencing was applied to multiple samples from each of 50 patients' tumors, finding thatLandmarks of disease progression arose within detectable subclones of antecedent lesions.
Journal ArticleDOI
Clinical drug response can be predicted using baseline gene expression levels and in vitro drug sensitivity in cell lines.
TL;DR: A method for the prediction of chemotherapeutic response in patients using only before-treatment baseline tumor gene expression data, validated in three independent clinical trial datasets, and obtained predictions equally good, or better, gene signatures derived directly from clinical data.
Journal ArticleDOI
Current Challenges in Cancer Treatment.
Jon Zugazagoitia,Cristiano Guedes,Santiago Ponce,Irene Ferrer,Sonia Molina-Pinelo,Luis Paz-Ares +5 more
TL;DR: This review highlights the current concepts and discusses some of the current challenges and future prospects in cancer therapy, and selects the most comprehensive and relevant research articles, clinical trials, translational papers, and review articles on precision oncology and immuno-oncology.
Journal ArticleDOI
Precision medicine for cancer with next-generation functional diagnostics
TL;DR: A future diagnostic strategy that integrates functional testing with next-generation sequencing and immunoprofiling to precisely match combination therapies to individual cancer patients is suggested.
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Intratumor heterogeneity and branched evolution revealed by multiregion sequencing.
Marco Gerlinger,Andrew Rowan,Stuart Horswell,James Larkin,David Endesfelder,Eva Grönroos,Pierre Martinez,Nicholas Matthews,Aengus Stewart,Patrick S. Tarpey,Ignacio Varela,Benjamin Phillimore,Sharmin Begum,Neil Q. McDonald,Adam Butler,David T. Jones,Keiran Raine,Calli Latimer,Claudio R. Santos,Mahrokh Nohadani,Aron Charles Eklund,Bradley Spencer-Dene,Graham Clark,Lisa Pickering,Gordon Stamp,Martin Gore,Zoltan Szallasi,Zoltan Szallasi,Julian Downward,P. Andrew Futreal,Charles Swanton +30 more
TL;DR: Intratumor heterogeneity can lead to underestimation of the tumor genomics landscape portrayed from single tumor-biopsy samples and may present major challenges to personalized-medicine and biomarker development.
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Identification of the transforming EML4–ALK fusion gene in non-small-cell lung cancer
Manabu Soda,Young Lim Choi,Munehiro Enomoto,Shuji Takada,Yoshihiro Yamashita,Shunpei Ishikawa,Shin-ichiro Fujiwara,Hideki Watanabe,Kentaro Kurashina,Hisashi Hatanaka,Masashi Bando,Shoji Ohno,Yuichi Ishikawa,Hiroyuki Aburatani,Toshiro Niki,Yasunori Sohara,Yukihiko Sugiyama,Hiroyuki Mano +17 more
TL;DR: It is shown that a small inversion within chromosome 2p results in the formation of a fusion gene comprising portions of the echinoderm microtubule-associated protein-like 4 (EML4) gene and the anaplastic lymphoma kinase (ALK) gene in non-small-cell lung cancer (NSCLC) cells.
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