In silico prescription of anticancer drugs to cohorts of 28 tumor types reveals targeting opportunities

Cancer Cell
Carlota Rubio-PerezNuria Lopez-Bigas

Abstract

Large efforts dedicated to detect somatic alterations across tumor genomes/exomes are expected to produce significant improvements in precision cancer medicine. However, high inter-tumor heterogeneity is a major obstacle to developing and applying therapeutic targeted agents to treat most cancer patients. Here, we offer a comprehensive assessment of the scope of targeted therapeutic agents in a large pan-cancer cohort. We developed an in silico prescription strategy based on identification of the driver alterations in each tumor and their druggability options. Although relatively few tumors are tractable by approved agents following clinical guidelines (5.9%), up to 40.2% could benefit from different repurposing options, and up to 73.3% considering treatments currently under clinical investigation. We also identified 80 therapeutically targetable cancer genes.

References

Jun 26, 2002·Cancer Gene Therapy·Richard E BullerMark Pegram
Mar 3, 2004·Nature Reviews. Cancer·P Andrew FutrealMichael R Stratton
Sep 10, 2008·Nature Biotechnology·Jordi MestresRicard V Solé
Oct 22, 2008·Nature Chemical Biology·Andrew L Hopkins
Jun 26, 2009·The New England Journal of Medicine·Peter C FongJohann S de Bono
Mar 8, 2011·Cell·Douglas Hanahan, Robert A Weinberg
Mar 26, 2011·Science·Michael R Stratton
Jul 27, 2011·Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology·Amit M OzaElizabeth A Eisenhauer
Sep 29, 2011·Nucleic Acids Research·Anna GaultonJohn P Overington
Oct 21, 2011·Nucleic Acids Research·Mark D Halling-BrownBissan Al-Lazikani
Jul 12, 2012·Nature Biotechnology·Bissan Al-LazikaniPaul Workman
Aug 21, 2012·Nucleic Acids Research·Abel Gonzalez-Perez, Nuria Lopez-Bigas
Nov 9, 2012·Clinical Chemistry·Jennifer Jennings, Thomas J Hudson
Jan 29, 2013·The Journal of Gene Medicine·Samantha L GinnJo Wixon
Mar 30, 2013·Science·Bert VogelsteinKenneth W Kinzler
Apr 2, 2013·Cell·Levi A Garraway, Eric S Lander
Apr 17, 2013·Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology·Levi A Garraway
Jun 19, 2013·Blood·Bartlomiej PrzychodzenHideki Makishima
Aug 1, 2013·Nature Methods·Abel Gonzalez-PerezUNKNOWN International Cancer Genome Consortium Mutation Pathways and Consequences Subgroup of the Bioinformatics Analyses Working Gr
Aug 10, 2013·Trends in Pharmacological Sciences·Subash C GuptaBharat B Aggarwal
Sep 17, 2013·Nature Methods·Abel Gonzalez-PerezNuria Lopez-Bigas
Sep 28, 2013·Nature Genetics·UNKNOWN Cancer Genome Atlas Research NetworkJoshua M Stuart
Oct 3, 2013·Scientific Reports·David TamboreroNuria Lopez-Bigas
Apr 29, 2014·Molecular Oncology·Rodrigo DienstmannA John Iafrate
Aug 28, 2014·Bioinformatics·Michael P SchroederNuria Lopez-Bigas

❮ Previous
Next ❯

Citations

Dec 15, 2015·Clinical Pharmacology and Therapeutics·B Chen, A J Butte
Jan 30, 2016·Nature Reviews. Cancer·Emmy D G FleurenRoger J Daly
Feb 24, 2016·ELife·Ed ReznikChris Sander
Mar 12, 2015·Cancer Cell·Emmanuel Martinez-LedesmaRoel G W Verhaak
Jul 22, 2015·Nature Reviews. Clinical Oncology·Monica ArnedosFabrice Andre
Nov 6, 2015·Nature Reviews. Cancer·Adam A FriedmanKeith T Flaherty
Jul 23, 2015·Nature·Xose S PuenteElías Campo
Mar 16, 2016·Future Medicinal Chemistry·Lirong Wang, Xiang-Qun Xie
Dec 29, 2015·Chembiochem : a European Journal of Chemical Biology·Daniel Varon Silva
Oct 17, 2015·Nanomedicine·Deniz Ali Bölükbas, Silke Meiners
Mar 31, 2016·Journal of the American Medical Informatics Association : JAMIA·Feixiong ChengZhongming Zhao
Oct 23, 2015·Genes & Diseases·Jing WangTong-Chuan He
Apr 25, 2015·Nature Reviews. Drug Discovery·Megan Cully
May 21, 2016·ACS Chemical Biology·Toru Komatsu, Satpal Virdee
Jun 21, 2016·Cancer Cell·Jakob HedegaardLars Dyrskjøt
Jul 12, 2016·Cell·Francesco IorioMathew J Garnett
Jul 16, 2016·Nature Communications·Matan HofreeTrey Ideker
Sep 15, 2016·Epigenomics·Aniruddha ChatterjeeMichael R Eccles
Sep 8, 2016·Proceedings of the National Academy of Sciences of the United States of America·Seung-Hyun JungSug Hyung Lee
Oct 8, 2016·Genome Medicine·Carlota Rubio-PerezAbel Gonzalez-Perez
Nov 1, 2016·Nature Genetics·Bishoy M FaltasMark A Rubin
Dec 3, 2016·Nucleic Acids Research·Gautier KoscielnyIan Dunham
Mar 30, 2017·Nature Communications·Kuan-Lin HuangLi Ding
Nov 12, 2016·Molecular & Cellular Proteomics : MCP·Jing WangBing Zhang
Jun 18, 2017·Expert Review of Proteomics·Mari Masuda, Tesshi Yamada
Oct 28, 2017·Briefings in Bioinformatics·Gonzalo Gómez-LópezFátima Al-Shahrour
May 3, 2018·Molecular Biology and Evolution·Atsushi NiidaHideki Innan
Mar 10, 2018·Nature Communications·Sai GeJun Qin

❮ Previous
Next ❯

Related Concepts

Related Feeds

Cancer Stem Cells in Glioblastoma

Glioblastoma is the most common and aggressive type of brain tumor. It contains a population of tumor initiating stem cell-like cells known as cancer stem cells. Investigations are ongoing into these cancer stem cells found in these solid tumors which are highly resistance to treatment. Here is the latest research on cancer stem cells in glioblastoma.

Cancer Genomics (Keystone)

Cancer genomics approaches employ high-throughput technologies to identify the complete catalog of somatic alterations that characterize the genome, transcriptome and epigenome of cohorts of tumor samples. Discover the latest research using such technologies in this feed.

Cancer Incidence & Mortality

Cancer has emerged as a global concern due to its increase in incidence and mortality. Efforts are underway to evaluate and develop action plans to reduce the global burden of cancer. Currently, lung cancer, breast cancer and prostate cancer are the leading causes of cancer mortality. Here is the latest research on cancer incidence and mortality.

Adenocarcinoma, Clear Cell

Clear Cell Adenocarcinoma is a tumor that arises in the female genital tract and is characterized by cells that appear clear under the microscope. Discover the latest research here.