Integrative omics analyses broaden treatment targets in human cancer

Sengupta, Sohini; Sun, Sam Q.; Huang, Kuan-lin; Oh, Clara; Bailey, Matthew H.; Varghese, Rajees; Wyczalkowski, Matthew A.; Ning, Jie; Tripathi, Piyush; McMichael, Joshua F.; Johnson, Kimberly J.; Kandoth, Cyriac; Welch, John; Ma, Cynthia; Wendl, Michael C.; Payne, Samuel H.; Fenyö, David; Townsend, Reid R.; Dipersio, John F.; Chen, Feng; Ding, Li

doi:10.1186/S13073-018-0564-Z

Title: Integrative omics analyses broaden treatment targets in human cancer

Journal Article · 27 July 2018 · Genome Medicine

DOI: https://doi.org/10.1186/S13073-018-0564-Z · OSTI ID:1463657

Sengupta, Sohini; Sun, Sam Q.; Huang, Kuan-lin; Oh, Clara; Bailey, Matthew H.; Varghese, Rajees; Wyczalkowski, Matthew A.; Ning, Jie; Tripathi, Piyush; McMichael, Joshua F.; Johnson, Kimberly J.; Kandoth, Cyriac; Welch, John; Ma, Cynthia; Wendl, Michael C.; Payne, Samuel H.; Fenyö, David; Townsend, Reid R.; Dipersio, John F.; Chen, Feng more »

Although large-scale, next-generation sequencing (NGS) studies of cancers hold promise for enabling precision oncology, challenges remain in integrating NGS with clinically validated biomarkers. To overcome such challenges, we utilized the Database of Evidence for Precision Oncology (DEPO) to link druggability to genomic, transcriptomic, and proteomic biomarkers. Using a pan-cancer cohort of 6570 tumors, we identified tumors with potentially druggable biomarkers consisting of drug-associated mutations, mRNA expression outliers, and protein/phosphoprotein expression outliers identified by DEPO. As a result, within the pan-cancer cohort of 6570 tumors, we found that 3% are druggable based on FDA-approved drug-mutation interactions in specific cancer types. However, mRNA/phosphoprotein/protein expression outliers and drug repurposing across cancer types suggest potential druggability in up to 16% of tumors. The percentage of potential drug-associated tumors can increase to 48% if we consider preclinical evidence. Further, our analyses showed co-occurring potentially druggable multi-omics alterations in 32% of tumors, indicating a role for individualized combinational therapy, with evidence supporting mTOR/PI3K/ESR1 co-inhibition and BRAF/AKT co-inhibition in 1.6 and 0.8% of tumors, respectively. We experimentally validated a subset of putative druggable mutations in BRAF identified by a protein structure-based computational tool. Finally, analysis of a large-scale drug screening dataset lent further evidence supporting repurposing of drugs across cancer types and the use of expression outliers for inferring druggability. Finally, our results suggest that an integrated analysis platform can nominate multi-omics alterations as biomarkers of druggability and aid ongoing efforts to bring precision oncology to patients.

View Accepted Manuscript (DOE)

Cite

Export

Save

Research Organization:: Pacific Northwest National Laboratory (PNNL), Richland, WA (United States)

Sponsoring Organization:: USDOE

Grant/Contract Number:: AC05-76RL01830; R01CA178383; R01CA180006; R01DK087960; U01HG006517

OSTI ID:: 1463657

Report Number(s):: PNNL-SA-138193; PII: 564

Journal Information:: Genome Medicine, Vol. 10, Issue 1; ISSN 1756-994X

Publisher:: BioMed Central (BMC)Copyright Statement

Country of Publication:: United States

Language:: English

Citation Metrics:

Cited by: 10 works

Citation information provided by
Web of Science

References (88)

Relationship between aspirin use after diagnosis of colorectal cancer and patient survival: a meta-analysis of observational studies Ye, X-F; Wang, J.; Shi, W-T British Journal of Cancer, Vol. 111, Issue 11 https://doi.org/10.1038/bjc.2014.481	journal	September 2014
Database of evidence for precision oncology portal Sun, Sam Q.; Mashl, R. Jay; Sengupta, Sohini Bioinformatics, Vol. 34, Issue 24 https://doi.org/10.1093/bioinformatics/bty531	journal	July 2018
Comparative genomic hybridisation array and DNA sequencing to direct treatment of metastatic breast cancer: a multicentre, prospective trial (SAFIR01/UNICANCER) André, Fabrice; Bachelot, Thomas; Commo, Frederic The Lancet Oncology, Vol. 15, Issue 3 https://doi.org/10.1016/S1470-2045(13)70611-9	journal	March 2014
Association of KRAS p.G13D Mutation With Outcome in Patients With Chemotherapy-Refractory Metastatic Colorectal Cancer Treated With Cetuximab De Roock, Wendy; Jonker, Derek J.; Di Nicolantonio, Federica JAMA, Vol. 304, Issue 16 https://doi.org/10.1001/jama.2010.1535	journal	October 2010
High-Throughput Detection of Actionable Genomic Alterations in Clinical Tumor Samples by Targeted, Massively Parallel Sequencing Wagle, Nikhil; Berger, Michael F.; Davis, Matthew J. Cancer Discovery, Vol. 2, Issue 1 https://doi.org/10.1158/2159-8290.CD-11-0184	journal	November 2011
Targeting HER2 with T-DM1, an Antibody Cytotoxic Drug Conjugate, is Effective in HER2 Over Expressing Bladder Cancer Hayashi, Tetsutaro; Seiler, Roland; Oo, Htoo Zarni Journal of Urology, Vol. 194, Issue 4 https://doi.org/10.1016/j.juro.2015.05.087	journal	October 2015
Discovery and saturation analysis of cancer genes across 21 tumour types Lawrence, Michael S.; Stojanov, Petar; Mermel, Craig H. Nature, Vol. 505, Issue 7484 https://doi.org/10.1038/nature12912	journal	January 2014
Using Multiplexed Assays of Oncogenic Drivers in Lung Cancers to Select Targeted Drugs Kris, Mark G.; Johnson, Bruce E.; Berry, Lynne D. JAMA, Vol. 311, Issue 19 https://doi.org/10.1001/jama.2014.3741	journal	May 2014
Mutational landscape and significance across 12 major cancer types Kandoth, Cyriac; McLellan, Michael D.; Vandin, Fabio Nature, Vol. 502, Issue 7471 https://doi.org/10.1038/nature12634	journal	October 2013
Clinical Actionability Enhanced through Deep Targeted Sequencing of Solid Tumors Chen, K.; Meric-Bernstam, F.; Zhao, H. Clinical Chemistry, Vol. 61, Issue 3 https://doi.org/10.1373/clinchem.2014.231100	journal	January 2015
Toward understanding and exploiting tumor heterogeneity Alizadeh, Ash A.; Aranda, Victoria; Bardelli, Alberto Nature Medicine, Vol. 21, Issue 8 https://doi.org/10.1038/nm.3915	journal	August 2015
In Silico Prescription of Anticancer Drugs to Cohorts of 28 Tumor Types Reveals Targeting Opportunities Rubio-Perez, Carlota; Tamborero, David; Schroeder, Michael P. Cancer Cell, Vol. 27, Issue 3 https://doi.org/10.1016/j.ccell.2015.02.007	journal	March 2015
ClinVar: public archive of relationships among sequence variation and human phenotype Landrum, Melissa J.; Lee, Jennifer M.; Riley, George R. Nucleic Acids Research, Vol. 42, Issue D1 https://doi.org/10.1093/nar/gkt1113	journal	November 2013
Epidermal Growth Factor Receptor Activation in Glioblastoma through Novel Missense Mutations in the Extracellular Domain Lee, Jeffrey C.; Vivanco, Igor; Beroukhim, Rameen PLoS Medicine, Vol. 3, Issue 12 https://doi.org/10.1371/journal.pmed.0030485	journal	December 2006
Whole-exome sequencing and clinical interpretation of formalin-fixed, paraffin-embedded tumor samples to guide precision cancer medicine Van Allen, Eliezer M.; Wagle, Nikhil; Stojanov, Petar Nature Medicine, Vol. 20, Issue 6 https://doi.org/10.1038/nm.3559	journal	May 2014
Fusion of EML4 and ALK is associated with development of lung adenocarcinomas lacking EGFR and KRAS mutations and is correlated with ALK expression Zhang, Xuchao; Zhang, Shirley; Yang, Xuening Molecular Cancer, Vol. 9, Issue 1 https://doi.org/10.1186/1476-4598-9-188	journal	January 2010
Genomics of Drug Sensitivity in Cancer (GDSC): a resource for therapeutic biomarker discovery in cancer cells Yang, Wanjuan; Soares, Jorge; Greninger, Patricia Nucleic Acids Research, Vol. 41, Issue D1 https://doi.org/10.1093/nar/gks1111	journal	November 2012
Assessing PIK3CA and PTEN in Early-Phase Trials with PI3K/AKT/mTOR Inhibitors Janku, Filip; Hong, David S.; Fu, Siqing Cell Reports, Vol. 6, Issue 2 https://doi.org/10.1016/j.celrep.2013.12.035	journal	January 2014
Estrogen- and Progesterone-Receptor Status in ECOG 2197: Comparison of Immunohistochemistry by Local and Central Laboratories and Quantitative Reverse Transcription Polymerase Chain Reaction by Central Laboratory Badve, Sunil S.; Baehner, Frederick L.; Gray, Robert P. Journal of Clinical Oncology, Vol. 26, Issue 15 https://doi.org/10.1200/JCO.2007.13.6424	journal	May 2008
Cancer Genome Landscapes Vogelstein, B.; Papadopoulos, N.; Velculescu, V. E. Science, Vol. 339, Issue 6127 https://doi.org/10.1126/science.1235122	journal	March 2013
Incidence of Invasive Breast Cancer by Hormone Receptor Status From 1992 to 1998 Li, Christopher I.; Daling, Janet R.; Malone, Kathleen E. Journal of Clinical Oncology, Vol. 21, Issue 1 https://doi.org/10.1200/JCO.2003.03.088	journal	January 2003
Down-modulation of an oncogene protein product and reversion of the transformed phenotype by monoclonal antibodies Drebin, Jeffrey A.; Link, Victoria C.; Stern, David F. Cell, Vol. 41, Issue 3 https://doi.org/10.1016/S0092-8674(85)80050-7	journal	July 1985
Phase II Trial of Bicalutamide in Patients with Androgen Receptor-Positive, Estrogen Receptor-Negative Metastatic Breast Cancer Gucalp, A.; Tolaney, S.; Isakoff, S. J. Clinical Cancer Research, Vol. 19, Issue 19 https://doi.org/10.1158/1078-0432.CCR-12-3327	journal	August 2013
Development and validation of a clinical cancer genomic profiling test based on massively parallel DNA sequencing Frampton, Garrett M.; Fichtenholtz, Alex; Otto, Geoff A. Nature Biotechnology, Vol. 31, Issue 11 https://doi.org/10.1038/nbt.2696	journal	October 2013
Combined BRAF and MEK Inhibition versus BRAF Inhibition Alone in Melanoma Long, Georgina V.; Stroyakovskiy, Daniil; Gogas, Helen New England Journal of Medicine, Vol. 371, Issue 20 https://doi.org/10.1056/NEJMoa1406037	journal	November 2014
HER2 Status and Benefit from Adjuvant Trastuzumab in Breast Cancer Paik, Soonmyung; Kim, Chungyeul; Wolmark, Norman New England Journal of Medicine, Vol. 358, Issue 13 https://doi.org/10.1056/NEJMc0801440	journal	March 2008
Everolimus in Postmenopausal Hormone-Receptor–Positive Advanced Breast Cancer Baselga, José; Campone, Mario; Piccart, Martine New England Journal of Medicine, Vol. 366, Issue 6 https://doi.org/10.1056/NEJMoa1109653	journal	February 2012
Considerations for the successful co-development of targeted cancer therapies and companion diagnostics Fridlyand, Jane; Simon, Richard M.; Walrath, Jessica C. Nature Reviews Drug Discovery, Vol. 12, Issue 10 https://doi.org/10.1038/nrd4101	journal	September 2013
BRAF mutant colorectal cancer: prognosis, treatment, and new perspectives Sanz-Garcia, E.; Argiles, G.; Elez, E. Annals of Oncology, Vol. 28, Issue 11 https://doi.org/10.1093/annonc/mdx401	journal	July 2017
Intratumor heterogeneity in human glioblastoma reflects cancer evolutionary dynamics Sottoriva, A.; Spiteri, I.; Piccirillo, S. G. M. Proceedings of the National Academy of Sciences, Vol. 110, Issue 10 https://doi.org/10.1073/pnas.1219747110	journal	February 2013
Estrogen Receptor ( ESR1 ) mRNA Expression and Benefit From Tamoxifen in the Treatment and Prevention of Estrogen Receptor–Positive Breast Cancer Kim, Chungyeul; Tang, Gong; Pogue-Geile, Katherine L. Journal of Clinical Oncology, Vol. 29, Issue 31 https://doi.org/10.1200/JCO.2010.32.9615	journal	November 2011
Treatment Algorithms Based on Tumor Molecular Profiling: The Essence of Precision Medicine Trials Le Tourneau, Christophe; Kamal, Maud; Tsimberidou, Apostolia-Maria Journal of the National Cancer Institute, Vol. 108, Issue 4 https://doi.org/10.1093/jnci/djv362	journal	November 2015
SIFT: predicting amino acid changes that affect protein function Ng, P. C. Nucleic Acids Research, Vol. 31, Issue 13 https://doi.org/10.1093/nar/gkg509	journal	July 2003
DGIdb: mining the druggable genome Griffith, Malachi; Griffith, Obi L.; Coffman, Adam C. Nature Methods, Vol. 10, Issue 12 https://doi.org/10.1038/nmeth.2689	journal	October 2013
The Ensembl genome database project Hubbard, T. Nucleic Acids Research, Vol. 30, Issue 1 https://doi.org/10.1093/nar/30.1.38	journal	January 2002
Inhibitory Fc receptors modulate in vivo cytoxicity against tumor targets Clynes, Raphael A.; Towers, Terri L.; Presta, Leonard G. Nature Medicine, Vol. 6, Issue 4 https://doi.org/10.1038/74704	journal	April 2000
The right drugs at the right time for the right patient: the MD Anderson precision oncology decision support platform Johnson, Amber; Zeng, Jia; Bailey, Ann M. Drug Discovery Today, Vol. 20, Issue 12 https://doi.org/10.1016/j.drudis.2015.05.013	journal	December 2015
A method and server for predicting damaging missense mutations Adzhubei, Ivan A.; Schmidt, Steffen; Peshkin, Leonid Nature Methods, Vol. 7, Issue 4 https://doi.org/10.1038/nmeth0410-248	journal	April 2010
CancerDR: Cancer Drug Resistance Database Kumar, Rahul; Chaudhary, Kumardeep; Gupta, Sudheer Scientific Reports, Vol. 3, Issue 1 https://doi.org/10.1038/srep01445	journal	March 2013
Dramatic Response Induced by Vemurafenib in a BRAF V600E-Mutated Lung Adenocarcinoma Peters, Solange; Michielin, Olivier; Zimmermann, Stefan Journal of Clinical Oncology, Vol. 31, Issue 20 https://doi.org/10.1200/JCO.2012.47.6143	journal	July 2013
Wild-Type KRAS Is Required for Panitumumab Efficacy in Patients With Metastatic Colorectal Cancer Amado, Rafael G.; Wolf, Michael; Peeters, Marc Journal of Clinical Oncology, Vol. 26, Issue 10 https://doi.org/10.1200/JCO.2007.14.7116	journal	April 2008
Systematic identification of genomic markers of drug sensitivity in cancer cells Garnett, Mathew J.; Edelman, Elena J.; Heidorn, Sonja J. Nature, Vol. 483, Issue 7391 https://doi.org/10.1038/nature11005	journal	March 2012
Randomized Phase II Study of Erlotinib Combined With Bevacizumab Compared With Bevacizumab Alone in Metastatic Renal Cell Cancer Bukowski, Ronald M.; Kabbinavar, Fairooz F.; Figlin, Robert A. Journal of Clinical Oncology, Vol. 25, Issue 29 https://doi.org/10.1200/JCO.2007.11.5154	journal	October 2007
The Origin and Evolution of Mutations in Acute Myeloid Leukemia Welch, John S.; Ley, Timothy J.; Link, Daniel C. Cell, Vol. 150, Issue 2 https://doi.org/10.1016/j.cell.2012.06.023	journal	July 2012
The RAC1 P29S Hotspot Mutation in Melanoma Confers Resistance to Pharmacological Inhibition of RAF Watson, Ian R.; Li, Liren; Cabeceiras, Peter K. Cancer Research, Vol. 74, Issue 17 https://doi.org/10.1158/0008-5472.CAN-14-1232-T	journal	July 2014
Proteogenomics connects somatic mutations to signalling in breast cancer Mertins, Philipp; Mani, D. R.; Ruggles, Kelly V. Nature, Vol. 534, Issue 7605 https://doi.org/10.1038/nature18003	journal	May 2016
Database of Genomic Biomarkers for Cancer Drugs and Clinical Targetability in Solid Tumors Dienstmann, Rodrigo; Jang, In Sock; Bot, Brian Cancer Discovery, Vol. 5, Issue 2 https://doi.org/10.1158/2159-8290.CD-14-1118	journal	February 2015
Protein-structure-guided discovery of functional mutations across 19 cancer types Niu, Beifang; Scott, Adam D.; Sengupta, Sohini Nature Genetics, Vol. 48, Issue 8 https://doi.org/10.1038/ng.3586	journal	June 2016
The Cancer Cell Line Encyclopedia enables predictive modelling of anticancer drug sensitivity Barretina, Jordi; Caponigro, Giordano; Stransky, Nicolas Nature, Vol. 483, Issue 7391 https://doi.org/10.1038/nature11003	journal	March 2012
Epidermal Growth Factor Receptor and Epidermal Growth Factor Receptor Therapies in Renal Cell Carcinoma: Do We Need a Better Mouse Trap? Dancey, Janet E. Journal of Clinical Oncology, Vol. 22, Issue 15 https://doi.org/10.1200/JCO.2004.04.934	journal	August 2004
Genomic Landscape of Non-Small Cell Lung Cancer in Smokers and Never-Smokers Govindan, Ramaswamy; Ding, Li; Griffith, Malachi Cell, Vol. 150, Issue 6 https://doi.org/10.1016/j.cell.2012.08.024	journal	September 2012
ERBB receptors and cancer: the complexity of targeted inhibitors Hynes, Nancy E.; Lane, Heidi A. Nature Reviews Cancer, Vol. 5, Issue 5 https://doi.org/10.1038/nrc1609	journal	May 2005
Estrogen receptor alpha (ESR1) gene amplification is frequent in breast cancer Holst, Frederik; Stahl, Phillip R.; Ruiz, Christian Nature Genetics, Vol. 39, Issue 5 https://doi.org/10.1038/ng2006	journal	April 2007
TCPA: a resource for cancer functional proteomics data Li, Jun; Lu, Yiling; Akbani, Rehan Nature Methods, Vol. 10, Issue 11 https://doi.org/10.1038/nmeth.2650	journal	September 2013
Integrated Proteogenomic Characterization of Human High-Grade Serous Ovarian Cancer Zhang, Hui; Liu, Tao; Zhang, Zhen Cell, Vol. 166, Issue 3 https://doi.org/10.1016/j.cell.2016.05.069	journal	July 2016
Panitumumab–FOLFOX4 Treatment and RAS Mutations in Colorectal Cancer Douillard, Jean-Yves; Oliner, Kelly S.; Siena, Salvatore New England Journal of Medicine, Vol. 369, Issue 11 https://doi.org/10.1056/NEJMoa1305275	journal	September 2013
Clinical efficacy of a RAF inhibitor needs broad target blockade in BRAF-mutant melanoma Bollag, Gideon; Hirth, Peter; Tsai, James Nature, Vol. 467, Issue 7315 https://doi.org/10.1038/nature09454	journal	September 2010
A Landscape of Pharmacogenomic Interactions in Cancer Iorio, Francesco; Knijnenburg, Theo A.; Vis, Daniel J. Cell, Vol. 166, Issue 3 https://doi.org/10.1016/j.cell.2016.06.017	journal	July 2016
Combination Targeted Therapy With Sorafenib and Bevacizumab Results in Enhanced Toxicity and Antitumor Activity Azad, Nilofer S.; Posadas, Edwin M.; Kwitkowski, Virginia E. Journal of Clinical Oncology, Vol. 26, Issue 22 https://doi.org/10.1200/JCO.2007.10.8332	journal	August 2008
Antitumor Activity in RAS-Driven Tumors by Blocking AKT and MEK Tolcher, A. W.; Khan, K.; Ong, M. Clinical Cancer Research, Vol. 21, Issue 4 https://doi.org/10.1158/1078-0432.CCR-14-1901	journal	December 2014
Lapatinib or Trastuzumab Plus Taxane Therapy for Human Epidermal Growth Factor Receptor 2–Positive Advanced Breast Cancer: Final Results of NCIC CTG MA.31 Gelmon, Karen A.; Boyle, Frances M.; Kaufman, Bella Journal of Clinical Oncology, Vol. 33, Issue 14 https://doi.org/10.1200/JCO.2014.56.9590	journal	May 2015
Whole-Exome Sequencing of Metastatic Cancer and Biomarkers of Treatment Response Beltran, Himisha; Eng, Kenneth; Mosquera, Juan Miguel JAMA Oncology, Vol. 1, Issue 4 https://doi.org/10.1001/jamaoncol.2015.1313	journal	July 2015
Efficacy of Gefitinib, an Inhibitor of the Epidermal Growth Factor Receptor Tyrosine Kinase, in Symptomatic Patients With Non–Small Cell Lung Cancer: A Randomized Trial Kris, Mark G.; Natale, Ronald B.; Herbst, Roy S. JAMA, Vol. 290, Issue 16 https://doi.org/10.1001/jama.290.16.2149	journal	October 2003
Aspirin Use, Tumor PIK3CA Mutation, and Colorectal-Cancer Survival Liao, Xiaoyun; Lochhead, Paul; Nishihara, Reiko New England Journal of Medicine, Vol. 367, Issue 17 https://doi.org/10.1056/NEJMoa1207756	journal	October 2012
Safety, Pharmacokinetics, and Activity of ABX-EGF, a Fully Human Anti–Epidermal Growth Factor Receptor Monoclonal Antibody in Patients With Metastatic Renal Cell Cancer Rowinsky, Eric K.; Schwartz, Garry H.; Gollob, Jared A. Journal of Clinical Oncology, Vol. 22, Issue 15 https://doi.org/10.1200/JCO.2004.11.061	journal	August 2004
Systematic Prioritization of Druggable Mutations in ∼5000 Genomes Across 16 Cancer Types Using a Structural Genomics-based Approach Zhao, Junfei; Cheng, Feixiong; Wang, Yuanyuan Molecular & Cellular Proteomics, Vol. 15, Issue 2 https://doi.org/10.1074/mcp.M115.053199	journal	December 2015
Radiotherapy plus Cetuximab for Squamous-Cell Carcinoma of the Head and Neck Bonner, James A.; Harari, Paul M.; Giralt, Jordi New England Journal of Medicine, Vol. 354, Issue 6 https://doi.org/10.1056/NEJMoa053422	journal	February 2006
Trastuzumab — Mechanism of Action and Use in Clinical Practice Hudis, Clifford A. New England Journal of Medicine, Vol. 357, Issue 1 https://doi.org/10.1056/NEJMra043186	journal	July 2007
Proteogenomic characterization of human colon and rectal cancer Zhang, Bing; Wang, Jing; Wang, Xiaojing Nature, Vol. 513, Issue 7518 https://doi.org/10.1038/nature13438	journal	July 2014
A DLL3-targeted antibody-drug conjugate eradicates high-grade pulmonary neuroendocrine tumor-initiating cells in vivo Saunders, Laura R.; Bankovich, Alexander J.; Anderson, Wade C. Science Translational Medicine, Vol. 7, Issue 302 https://doi.org/10.1126/scitranslmed.aac9459	journal	August 2015
A Description of the Clinical Proteomic Tumor Analysis Consortium (CPTAC) Common Data Analysis Pipeline Rudnick, Paul A.; Markey, Sanford P.; Roth, Jeri Journal of Proteome Research, Vol. 15, Issue 3 https://doi.org/10.1021/acs.jproteome.5b01091	journal	February 2016
Humanization of an anti-p185HER2 antibody for human cancer therapy. Carter, P.; Presta, L.; Gorman, C. M. Proceedings of the National Academy of Sciences, Vol. 89, Issue 10, p. 4285-4289 https://doi.org/10.1073/pnas.89.10.4285	journal	May 1992
A Phase II Trial of Gefitinib (Iressa, ZD1839) in Stage IV and Recurrent Renal Cell Carcinoma Dawson, N. A. Clinical Cancer Research, Vol. 10, Issue 23 https://doi.org/10.1158/1078-0432.CCR-04-0310	journal	December 2004
My Cancer Genome: a unified genomics and clinical trial portal Swanton, Charles The Lancet Oncology, Vol. 13, Issue 7 https://doi.org/10.1016/S1470-2045(12)70312-1	journal	July 2012
NRAS-mutant melanoma: current challenges and future prospect Muñoz-Couselo, Eva; Zamora Adelantado, Ester; Ortiz Vélez, Carolina OncoTargets and Therapy, Vol. Volume 10 https://doi.org/10.2147/OTT.S117121	journal	January 2017
Half or more of the somatic mutations in cancers of self-renewing tissues originate prior to tumor initiation Tomasetti, C.; Vogelstein, B.; Parmigiani, G. Proceedings of the National Academy of Sciences, Vol. 110, Issue 6 https://doi.org/10.1073/pnas.1221068110	journal	January 2013
Comprehensive assessment of cancer missense mutation clustering in protein structures Kamburov, Atanas; Lawrence, Michael S.; Polak, Paz Proceedings of the National Academy of Sciences, Vol. 112, Issue 40 https://doi.org/10.1073/pnas.1516373112	journal	September 2015
Personalized Oncology Through Integrative High-Throughput Sequencing: A Pilot Study Roychowdhury, S.; Iyer, M. K.; Robinson, D. R. Science Translational Medicine, Vol. 3, Issue 111 https://doi.org/10.1126/scitranslmed.3003161	journal	November 2011
The landscape and therapeutic relevance of cancer-associated transcript fusions Yoshihara, K.; Wang, Q.; Torres-Garcia, W. Oncogene, Vol. 34, Issue 37 https://doi.org/10.1038/onc.2014.406	journal	December 2014
A Phase II Study of the Efficacy and Safety of the Combination Therapy of the MEK Inhibitor Refametinib (BAY 86-9766) Plus Sorafenib for Asian Patients with Unresectable Hepatocellular Carcinoma Lim, H. Y.; Heo, J.; Choi, H. J. Clinical Cancer Research, Vol. 20, Issue 23 https://doi.org/10.1158/1078-0432.CCR-13-3445	journal	October 2014
The landscape of precision cancer medicine clinical trials in the United States Roper, Nitin; Stensland, Kristian D.; Hendricks, Ryan Cancer Treatment Reviews, Vol. 41, Issue 5 https://doi.org/10.1016/j.ctrv.2015.02.009	journal	May 2015
Non-V600 BRAF mutations recurrently found in lung cancer predict sensitivity to the combination of Trametinib and Dabrafenib Noeparast, Amir; Teugels, Erik; Giron, Philippe Oncotarget, Vol. 8, Issue 36 https://doi.org/10.18632/oncotarget.11635	journal	August 2016
Phase I first-in-human study of HLX07, a novel and improved recombinant anti-EGFR humanized monoclonal antibody, in patients with advanced solid cancers Hou, Ming-Mo; Ho, Ching-Liang; Lin, Hsuan-Yu Investigational New Drugs https://doi.org/10.1007/s10637-021-01099-1	journal	March 2021
Unexpected Benefit from Alpelisib and Fulvestrant in a Woman with Highly Pre-treated ER-Positive, HER2-Negative PIK3CA Mutant Metastatic Breast Cancer Hoste, Griet; Slembrouck, Laurence; Jongen, Lynn Clinical Drug Investigation, Vol. 38, Issue 11 https://doi.org/10.1007/s40261-018-0696-3	journal	September 2018
PIM1 mediates epithelial-mesenchymal transition by targeting Smads and c-Myc in the nucleus and potentiates clear-cell renal-cell carcinoma oncogenesis Zhao, Bin; Liu, Lei; Mao, Jun Cell Death & Disease, Vol. 9, Issue 3 https://doi.org/10.1038/s41419-018-0348-9	journal	February 2018
OncoOmics approaches to reveal essential genes in breast cancer: a panoramic view from pathogenesis to precision medicine López-Cortés, Andrés; Paz-y-Miño, César; Guerrero, Santiago Scientific Reports, Vol. 10, Issue 1 https://doi.org/10.1038/s41598-020-62279-2	journal	March 2020
Proteogenomics connects somatic mutations to signalling in breast cancer Ping, Yan,; Francesca, Petralia,; Pei, Wang, The University of North Carolina at Chapel Hill University Libraries https://doi.org/10.17615/mepw-5x28	text	January 2016
An integrated map of genetic variation from 1,092 human genomes Yun, Li, The University of North Carolina at Chapel Hill University Libraries https://doi.org/10.17615/rsw4-ne53	text	January 2012

Cited By (2)

Integrative molecular analysis of metastatic hepatocellular carcinoma Wang, Dongfang; Zhu, Yanjing; Tang, Jing BMC Medical Genomics, Vol. 12, Issue 1 https://doi.org/10.1186/s12920-019-0586-4	journal	November 2019
Targeted Therapy Against the Cell of Origin in Cutaneous Squamous Cell Carcinoma Goldie, Stephen J.; Chincarini, Ginevra; Darido, Charbel International Journal of Molecular Sciences, Vol. 20, Issue 9 https://doi.org/10.3390/ijms20092201	journal	May 2019

Linked Research (8)

Figures / Tables (8)

Similar Records

Jiangsu Nanjing – Lawrence Berkeley Life Sciences Center for Translational Medicine (CRADA AWD00000392)

Technical Report · 2019 · OSTI ID:1576564

Karpen, Gary

Prognostic, predictive, and pharmacogenomic assessments of CDX 2 refine stratification of colorectal cancer

Journal Article · 2018 · Moletular Oncology · OSTI ID:1632044

Bruun, Jarle; Sveen, Anita; Barros, Rita; +11 more

Frequencies and expression levels of programmed death ligand 1 (PD-L1) in circulating tumor RNA (ctRNA) in various cancer types

Journal Article · 2018 · Biochemical and Biophysical Research Communications · OSTI ID:23125164

Ishiba, Toshiyuki; Hoffmann, Andreas-Claudius; Usher, Joshua; +3 more

Related Subjects

60 APPLIED LIFE SCIENCES
cancer genomics
mult-omics
proteogenomics
precision medicine
cancer and druggability

Additional file 1: of Integrative omics analyses broaden treatment targets in human cancer Sengupta, Sohini; Sun, Sam; Huang, Kuan-lin https://doi.org/10.6084/m9.figshare.6874364 The current record is supplemented by this dataset	dataset	July 2018
Additional file 1: of Integrative omics analyses broaden treatment targets in human cancer Sengupta, Sohini; Sun, Sam; Huang, Kuan-lin https://doi.org/10.6084/m9.figshare.6874364.v1 The current record is supplemented by this dataset	dataset	July 2018
Additional file 2: of Integrative omics analyses broaden treatment targets in human cancer Sun, Sam; Oh, Clara; Bailey, Matthew https://doi.org/10.6084/m9.figshare.6874382 The current record is supplemented by this dataset	dataset	July 2018
Additional file 3: of Integrative omics analyses broaden treatment targets in human cancer Sengupta, Sohini; Sun, Sam; Huang, Kuan-lin https://doi.org/10.6084/m9.figshare.6874406 The current record is supplemented by this dataset	dataset	July 2018
Additional file 3: of Integrative omics analyses broaden treatment targets in human cancer Sengupta, Sohini; Sun, Sam; Huang, Kuan-lin https://doi.org/10.6084/m9.figshare.6874406.v1 The current record is supplemented by this dataset	dataset	July 2018
Integrative omics analyses broaden treatment targets in human cancer [Supplementary Data] Sengupta, Sohini; Sun, Sam; Huang, Kuan-lin https://doi.org/10.6084/m9.figshare.c.4181018 The current record is supplemented by this collection	collection	July 2018
Integrative omics analyses broaden treatment targets in human cancer [Supplemental Data] Sun, Sam; Oh, Clara; Bailey, Matthew https://doi.org/10.6084/m9.figshare.c.4181018.v1 The current record is supplemented by this collection	collection	July 2018
Additional file 2: of Integrative omics analyses broaden treatment targets in human cancer Sengupta, Sohini; Sun, Sam; Huang, Kuan-lin https://doi.org/10.6084/m9.figshare.6874382.v1 The current record is supplemented by this dataset	dataset	July 2018