scispace - formally typeset
Search or ask a question
Author

Antonio Jimeno

Bio: Antonio Jimeno is an academic researcher from University of Colorado Boulder. The author has contributed to research in topics: Cancer & Head and neck squamous-cell carcinoma. The author has an hindex of 66, co-authored 305 publications receiving 19794 citations. Previous affiliations of Antonio Jimeno include Anschutz Medical Campus & Johns Hopkins University School of Medicine.


Papers
More filters
Journal ArticleDOI
26 Sep 2008-Science
TL;DR: It is found that pancreatic cancers contain an average of 63 genetic alterations, the majority of which are point mutations, which defined a core set of 12 cellular signaling pathways and processes that were each genetically altered in 67 to 100% of the tumors.
Abstract: There are currently few therapeutic options for patients with pancreatic cancer, and new insights into the pathogenesis of this lethal disease are urgently needed. Toward this end, we performed a comprehensive genetic analysis of 24 pancreatic cancers. We first determined the sequences of 23,219 transcripts, representing 20,661 protein-coding genes, in these samples. Then, we searched for homozygous deletions and amplifications in the tumor DNA by using microarrays containing probes for approximately 10(6) single-nucleotide polymorphisms. We found that pancreatic cancers contain an average of 63 genetic alterations, the majority of which are point mutations. These alterations defined a core set of 12 cellular signaling pathways and processes that were each genetically altered in 67 to 100% of the tumors. Analysis of these tumors' transcriptomes with next-generation sequencing-by-synthesis technologies provided independent evidence for the importance of these pathways and processes. Our data indicate that genetically altered core pathways and regulatory processes only become evident once the coding regions of the genome are analyzed in depth. Dysregulation of these core pathways and processes through mutation can explain the major features of pancreatic tumorigenesis.

3,721 citations

Journal ArticleDOI
Katherine A Hoadley1, Christina Yau2, Christina Yau3, Toshinori Hinoue4  +735 moreInstitutions (16)
05 Apr 2018-Cell
TL;DR: Molecular similarities among histologically or anatomically related cancer types provide a basis for focused pan-cancer analyses, such as pan-gastrointestinal, Pan-gynecological, pan-kidney, and pan-squamous cancers, and those related by stemness features, which may inform strategies for future therapeutic development.

1,535 citations

Journal ArticleDOI
TL;DR: This Review will discuss specific PDTX disease examples illustrating an overview of the opportunities and limitations of these models in cancer drug development, and describe concepts regarding predictive biomarker development and future applications.
Abstract: Progress in oncology drug development has been hampered by a lack of preclinical models that reliably predict clinical activity of novel compounds in cancer patients. In an effort to address these shortcomings, there has been a recent increase in the use of patient-derived tumour xenografts (PDTX) engrafted into immune-compromised rodents such as athymic nude or NOD/SCID mice for preclinical modelling. Numerous tumour-specific PDTX models have been established and, importantly, they are biologically stable when passaged in mice in terms of global gene-expression patterns, mutational status, metastatic potential, drug responsiveness and tumour architecture. These characteristics might provide significant improvements over standard cell-line xenograft models. This Review will discuss specific PDTX disease examples illustrating an overview of the opportunities and limitations of these models in cancer drug development, and describe concepts regarding predictive biomarker development and future applications.

1,093 citations

Journal ArticleDOI
TL;DR: This review summarizes the rationale, preclinical evidence, retrospective clinical analyses, and the interim clinical data pertaining HER2 therapies in gastric cancer.

997 citations

Journal ArticleDOI
Ezra E.W. Cohen1, Denis Soulières2, Christophe Le Tourneau3, Christophe Le Tourneau4, Christophe Le Tourneau5, José Dinis6, Lisa Licitra7, Myung-Ju Ahn8, Ainara Soria, Jean-Pascal Machiels9, Jean-Pascal Machiels10, Nicolas Mach, Ranee Mehra11, Barbara Burtness12, Pingye Zhang13, Jonathan D. Cheng13, Ramona F. Swaby13, Kevin J. Harrington14, Kevin J. Harrington15, Mirelis Acosta-Rivera, Douglas Adkins, Morteza Aghmesheh, Mario Airoldi, Eduardas Aleknavicius, Yousuf Al-Farhat, Alain Algazi, Salah Almokadem, Anna Alyasova, Jessica Bauman, Marco Benasso, Alfonso Berrocal, Victoria Bray, Barbara Ann Burtness12, F. Caponigro, Ana Castro, Terrence P. Cescon, Kelvin K. W. Chan, Arvind Chaudhry, Bruno Chauffert, Ezra W. Cohen1, Tibor Csoszi, J. de Boer, Jean-Pierre Delord, Andreas Dietz, Charlotte Dupuis, Laurence Digue, Jozsef Erfan, Yolanda Alvarez, Mererid Evans, Mary J. Fidler, Martin David Forster, Signe Friesland, Apar Kishor Ganti, Lionnel Geoffrois, Cliona Grant, Viktor Gruenwald, Kevin J. Harrington14, Thomas K. Hoffmann, Geza Horvai, Arturas Inciura, Raymond Woo-Jun Jang, Petra Jankowska, Antonio Jimeno, Mano Joseph, Alejandro Juarez Ramiro, Boguslawa Karaszewska, Andrzej Kawecki, Ulrich Keilholz, Ulrich Keller, Sung Bae Kim, Judit Kocsis, Nuria Kotecki, Mark F. Kozloff, Julio Lambea, Laszlo Landherr, Yuri Lantsukhay, Sergey Alexandrovich Lazarev, Lip Way Lee, Igor Dmitrievich Lifirenko, Danko Martincic, Oleg Vladmirovhich Matorin, Margaret McGrath, Krzysztof Misiukiewicz, John C. Morris, Fagim Fanisovich Mufazalov, Jiaxin Niu, Devraj Pamoorthy Srinivasan, Pedro Perez Segura, Daniel Rauch, Maria Leonor Ribeiro, Cristina P. Rodriguez, Frederic Rolland, Antonio Russo, Agnes Ruzsa, Frederico Sanches, Sang-Won Shin, Mikhail Shtiveland, Pol Specenier, Eva Szekanecz, Judit Szota, Carla M.L. van Herpen, Hector A. Velez-Cortes, William V. Walsh, Stefan Wilop, Ralph Winterhalder, Marek Z. Wojtukiewicz, Deborah Wong, Dan P. Zandberg 
TL;DR: The clinically meaningful prolongation of overall survival and favourable safety profile of pembrolizumab in patients with recurrent or metastatic head and neck squamous cell carcinoma support the further evaluation of p embrolizUMab as a monotherapy and as part of combination therapy in earlier stages of disease.

984 citations


Cited by
More filters
Journal ArticleDOI
25 Nov 2009-Cell
TL;DR: The mesenchymal state is associated with the capacity of cells to migrate to distant organs and maintain stemness, allowing their subsequent differentiation into multiple cell types during development and the initiation of metastasis.

8,642 citations

Journal ArticleDOI
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.
Abstract: Background Intratumor heterogeneity may foster tumor evolution and adaptation and hinder personalized-medicine strategies that depend on results from single tumor-biopsy samples. Methods To examine intratumor heterogeneity, we performed exome sequencing, chromosome aberration analysis, and ploidy profiling on multiple spatially separated samples obtained from primary renal carcinomas and associated metastatic sites. We characterized the consequences of intratumor heterogeneity using immunohistochemical analysis, mutation functional analysis, and profiling of messenger RNA expression. Results Phylogenetic reconstruction revealed branched evolutionary tumor growth, with 63 to 69% of all somatic mutations not detectable across every tumor region. Intratumor heterogeneity was observed for a mutation within an autoinhibitory domain of the mammalian target of rapamycin (mTOR) kinase, correlating with S6 and 4EBP phosphorylation in vivo and constitutive activation of mTOR kinase activity in vitro. Mutational intratumor heterogeneity was seen for multiple tumor-suppressor genes converging on loss of function; SETD2, PTEN, and KDM5C underwent multiple distinct and spatially separated inactivating mutations within a single tumor, suggesting convergent phenotypic evolution. Gene-expression signatures of good and poor prognosis were detected in different regions of the same tumor. Allelic composition and ploidy profiling analysis revealed extensive intratumor heterogeneity, with 26 of 30 tumor samples from four tumors harboring divergent allelic-imbalance profiles and with ploidy heterogeneity in two of four tumors. Conclusions 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. Intratumor heterogeneity, associated with heterogeneous protein function, may foster tumor adaptation and therapeutic failure through Darwinian selection. (Funded by the Medical Research Council and others.)

6,672 citations

Journal ArticleDOI
29 Mar 2013-Science
TL;DR: This work has revealed the genomic landscapes of common forms of human cancer, which consists of a small number of “mountains” (genes altered in a high percentage of tumors) and a much larger number of "hills" (Genes altered infrequently).
Abstract: Over the past decade, comprehensive sequencing efforts have revealed the genomic landscapes of common forms of human cancer. For most cancer types, this landscape consists of a small number of “mountains” (genes altered in a high percentage of tumors) and a much larger number of “hills” (genes altered infrequently). To date, these studies have revealed ~140 genes that, when altered by intragenic mutations, can promote or “drive” tumorigenesis. A typical tumor contains two to eight of these “driver gene” mutations; the remaining mutations are passengers that confer no selective growth advantage. Driver genes can be classified into 12 signaling pathways that regulate three core cellular processes: cell fate, cell survival, and genome maintenance. A better understanding of these pathways is one of the most pressing needs in basic cancer research. Even now, however, our knowledge of cancer genomes is sufficient to guide the development of more effective approaches for reducing cancer morbidity and mortality.

6,441 citations

Journal ArticleDOI
26 Sep 2008-Science
TL;DR: Recurrent mutations in the active site of isocitrate dehydrogenase 1 (IDH1) occurred in a large fraction of young patients and in most patients with secondary GBMs and were associated with an increase in overall survival.
Abstract: Glioblastoma multiforme (GBM) is the most common and lethal type of brain cancer. To identify the genetic alterations in GBMs, we sequenced 20,661 protein coding genes, determined the presence of amplifications and deletions using high-density oligonucleotide arrays, and performed gene expression analyses using next-generation sequencing technologies in 22 human tumor samples. This comprehensive analysis led to the discovery of a variety of genes that were not known to be altered in GBMs. Most notably, we found recurrent mutations in the active site of isocitrate dehydrogenase 1 (IDH1) in 12% of GBM patients. Mutations in IDH1 occurred in a large fraction of young patients and in most patients with secondary GBMs and were associated with an increase in overall survival. These studies demonstrate the value of unbiased genomic analyses in the characterization of human brain cancer and identify a potentially useful genetic alteration for the classification and targeted therapy of GBMs.

5,250 citations