Breakthrough cancer genome analysis in time and space: novel oncotargets and early drug development

Published on Nov 1, 2018in Pharmacogenomics2.265
· DOI :10.2217/pgs-2018-0141
Ioannis D Kyrochristos3
Estimated H-index: 3
Demosthenes E Ziogas5
Estimated H-index: 5
+ 3 AuthorsDimitrios H Roukos4
Estimated H-index: 4
(Academy of Athens)
  • References (25)
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Last. Dimitrios H Roukos (Academy of Athens)H-Index: 4
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Despite standardization of multimodal treatment and approval of several targeted drugs for resectable, non-metastatic cancer (M0 patients), intrinsic and acquired resistance and relapse rates remain high, even in early-stage aggressive tumors. Genome analysis could overcome these unmet needs. Our comprehensive review underlines the controversy on stable or spatiotemporally evolving clones as well as promising yet inconclusive data on genome-based biomarkers and drug development. We propose clini...
7 CitationsSource
#1Amritha Nair (BCM: Baylor College of Medicine)H-Index: 2
#2Hsiang-Ching Chung (BCM: Baylor College of Medicine)H-Index: 1
Last. Thomas F. Westbrook (BCM: Baylor College of Medicine)H-Index: 28
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Targeting tyrosine kinase receptors that share the feedback inhibitor PTPN12 leads to broad spectrum therapeutic suppression of triple-negative breast cancer.
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#1David M. Hyman (MSK: Memorial Sloan Kettering Cancer Center)H-Index: 35
#2Sarina Anne Piha-Paul (University of Texas MD Anderson Cancer Center)H-Index: 32
Last. David B. Solit (MSK: Memorial Sloan Kettering Cancer Center)H-Index: 83
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In a basket trial design, the efficacy of the pan-HER kinase inhibitor neratinib is tested in patients with 21 different tumour types, and responses are determined by mutation and tissue type, and are restricted to HER2-mutant cancers.
109 CitationsSource
#1Valérie Turcot (UdeM: Université de Montréal)H-Index: 7
#2Yingchang Lu (ISMMS: Icahn School of Medicine at Mount Sinai)H-Index: 38
Last. Ruth Loos (ISMMS: Icahn School of Medicine at Mount Sinai)H-Index: 111
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Genome-wide association studies (GWAS) have identified >250 loci for body mass index (BMI), implicating pathways related to neuronal biology. Most GWAS loci represent clusters of common, noncoding variants from which pinpointing causal genes remains challenging. Here we combined data from 718,734 individuals to discover rare and low-frequency (minor allele frequency (MAF) < 5%) coding variants associated with BMI. We identified 14 coding variants in 13 genes, of which 8 variants were in genes (Z...
76 CitationsSource
#1Wen-Zhao Zhong (Academy of Medical Sciences, United Kingdom)H-Index: 18
#2Qun Wang (Fudan University)H-Index: 2
Last. Jianhua ShiH-Index: 5
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Summary Background Cisplatin-based adjuvant chemotherapy is the standard of care for patients with resected stage II–IIIA non-small-cell lung cancer (NSCLC). RADIANT and SELECT trial data suggest patients with EGFR-mutant stage IB–IIIA resected NSCLC could benefit from adjuvant EGFR tyrosine kinase inhibitor treatment. We aimed to compare the efficacy of adjuvant gefitinib versus vinorelbine plus cisplatin in patients with completely resected EGFR-mutant stage II–IIIA (N1–N2) NSCLC. Methods We d...
43 CitationsSource
#1Shirley Yin-Yu Pang (HKU: University of Hong Kong)H-Index: 9
#2Kc Teo (HKU: University of Hong Kong)H-Index: 9
Last. Shu-Leong Ho (HKU: University of Hong Kong)H-Index: 30
view all 7 authors...
The clinical diagnosis of neurodegenerative disorders based on phenotype is difficult in heterogeneous conditions with overlapping symptoms. It does not take into account the disease etiology or the highly variable clinical course even amongst patients diagnosed with the same disorder. The advent of next generation sequencing (NGS) has allowed for a system-wide, unbiased approach to identify all gene variants in the genome simultaneously. With the plethora of new genes being identified, genetic ...
9 CitationsSource
The unmet clinical needs of high relapse and cancer-related death rates are reflected by the poor understanding of the genome-wide mutational landscape and molecular mechanisms orchestrating therapeutic resistance. Emerging potential solutions to this challenge include the exploration of cancer genome dynamic evolution in time and space. Breakthrough next-generation sequencing (NGS) applications including multiregional NGS for intratumor heterogeneity identification, repeated cell-free DNA/circu...
18 CitationsSource
BackgroundAmong patients with non–small-cell lung cancer (NSCLC), data on intratumor heterogeneity and cancer genome evolution have been limited to small retrospective cohorts. We wanted to prospectively investigate intratumor heterogeneity in relation to clinical outcome and to determine the clonal nature of driver events and evolutionary processes in early-stage NSCLC. MethodsIn this prospective cohort study, we performed multiregion whole-exome sequencing on 100 early-stage NSCLC tumors that ...
438 CitationsSource
#1Adrian AllyH-Index: 31
#2Miruna BalasundaramH-Index: 27
Last. Peter W. LairdH-Index: 97
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Summary Liver cancer has the second highest worldwide cancer mortality rate and has limited therapeutic options. We analyzed 363 hepatocellular carcinoma (HCC) cases by whole-exome sequencing and DNA copy number analyses, and we analyzed 196 HCC cases by DNA methylation, RNA, miRNA, and proteomic expression also. DNA sequencing and mutation analysis identified significantly mutated genes, including LZTR1 , EEF1A1 , SF3B1 , and SMARCA4 . Significant alterations by mutation or downregulation by hy...
314 CitationsSource
#1Nicholas K. Hayward (USYD: University of Sydney)H-Index: 83
#2James S. Wilmott (USYD: University of Sydney)H-Index: 36
Last. Graham J. Mann (USYD: University of Sydney)H-Index: 54
view all 49 authors...
Melanoma of the skin is a common cancer only in Europeans, whereas it arises in internal body surfaces (mucosal sites) and on the hands and feet (acral sites) in people throughout the world. Here we report analysis of whole-genome sequences from cutaneous, acral and mucosal subtypes of melanoma. The heavily mutated landscape of coding and non-coding mutations in cutaneous melanoma resolved novel signatures of mutagenesis attributable to ultraviolet radiation. However, acral and mucosal melanomas...
239 CitationsSource
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