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Machine Learning Detects Pan-cancer Ras Pathway Activation in The Cancer Genome Atlas

Gregory P. Way, Francisco Sanchez-Vega, Konnor La, Joshua Armenia, Walid K. Chatila, Augustin Luna, Chris Sander, Andrew D. Cherniack, Marco Mina, Giovanni Ciriello, Nikolaus Schultz, Yolanda Sanchez (+726 others)
2018 Cell Reports  
The transcriptome is underused in precision oncology and, combined with machine learning, can aid in the identification of hidden responders.  ...  Applied to the Ras pathway, the method detects Ras activation across cancer types and identifies phenocopying variants.  ...  We applied our method across cancer types to learn an independent, pan-cancer signature of pathway aberration.  ... 
doi:10.1016/j.celrep.2018.03.046 pmid:29617658 pmcid:PMC5918694 fatcat:a2myugjuhjfsldnfnftc6aauq4

Genomic pan-cancer classification using image-based deep learning

Taoyu Ye, Sen Li, Yang Zhang
2021 Computational and Structural Biotechnology Journal  
Powered by the deep learning, this approach can potentially provide a new solution for pan-cancer classification and cancer driver gene discovery.  ...  To circumvent this problem, a novel image-based deep learning strategy is employed to distinguish different types of cancer.  ...  By comparing differences in pathways between those two different types of cancers, many other signaling pathways are also involved in the pathogenesis of breast cancer, such as Ras, MAPK, TGF-beta, AMPK  ... 
doi:10.1016/j.csbj.2021.01.010 pmid:33598099 pmcid:PMC7848437 fatcat:fhw7y5evnzgjrkbclf5qhizlh4

Building patient-specific models for receptor tyrosine kinase signaling networks

Kyoichi Ebata, Sawa Yamashiro, Keita Iida, Mariko Okada
2021 The FEBS Journal  
Cancer progresses due to changes in the dynamic interactions of multidimensional factors associated with gene mutations.  ...  and diversity of cancers.  ...  Conflicts of interest The authors declare no conflict of interest. References  ... 
doi:10.1111/febs.15831 pmid:33755310 fatcat:eobfm6tbdbhz3b2tddgrg3ktyi

New Strategies in Endometrial Cancer: Targeting the PI3K/mTOR Pathway--The Devil Is in the Details

A. P. Myers
2013 Clinical Cancer Research  
Endometrial cancers harbor the highest rates of PI3K pathway alterations reported to date.  ...  The PI3K pathway is highly druggable and several classes of agents are in clinical development including rapalogs, pan-PI3K inhibitors, PI3K isoform-specific inhibitors, dual PI3K/mTOR catalytic inhibitors  ...  that is associated with PI3K pathway activation (41) .  ... 
doi:10.1158/1078-0432.ccr-13-0615 pmid:24089439 fatcat:c5m7kzeaizeudmgs5zhybrylzy

KRAS: The Critical Driver and Therapeutic Target for Pancreatic Cancer

Andrew M. Waters, Channing J. Der
2017 Cold Spring Harbor Perspectives in Medicine  
With the highest RAS mutation frequencies seen with the top three causes of cancer deaths in the United States (lung, colorectal, and pancreatic cancer), the development of anti-RAS therapies is a major  ...  With the KRAS isoform mutated in 84% of all RAS-mutant cancers, we focus on KRAS.  ...  Our research is funded by grants from the National Cancer Institute (CA042978, CA175747, CA199235, CA203657, and CA196510), the Department of Defense, the Pancreatic Cancer Action Network/American Association  ... 
doi:10.1101/cshperspect.a031435 pmid:29229669 fatcat:l642nud56ngczb23ekzcr2fiyi

PI3K and cancer: lessons, challenges and opportunities

David A. Fruman, Christian Rommel
2014 Nature reviews. Drug discovery  
In our opinion, enthusiasm and commitment towards targeting such an important pathway in cancer should not be reduced.  ...  Overview of the PI3K/AKT/mTOR signaling network Key features of the PI3K/AKT/mTOR signaling network that illustrate both the promise and the challenges for targeting the pathway in cancer have been previously  ...  Identification of S664 TSC2 phosphorylation as a marker for extracellular signal-regulated kinase mediated mTOR activation in tuberous sclerosis and human cancer. Cancer Res 67, 7106-12 (2007). 64.  ... 
doi:10.1038/nrd4204 pmid:24481312 pmcid:PMC3994981 fatcat:nnllsriyo5egjd52cggmioh6ku

Integrated Phosphoproteomics and Transcriptional Classifiers Reveal Hidden RAS Signaling Dynamics in Multiple Myeloma [article]

Yu-Hsiu Tony Lin, Gregory P. Way, Benjamin G. Barwick, Margarette C. Mariano, Makeba Marcoulis, Ian D. Ferguson, Christoph Driessen, Lawrence H. Boise, Casey S. Greene, Arun P. Wiita
2019 bioRxiv   pre-print
Transcriptional analysis suggests that aberrant MAPK pathway activation is only present in a fraction of RAS-mutated vs. WT RAS patients.  ...  These results may lead to improved stratification of MM patients in clinical trials while also revealing unexplored modes of Ras biology.  ...  Machine Learning Detects Pan-cancer Ras Pathway Activation in The Cancer Genome Atlas. Cell Rep 23, 172-180 e173 (2018). 31. Guinney, J., et al.  ... 
doi:10.1101/563312 fatcat:7aj6bvqh6zaozccb4yoxixirpi

The Rasopathy family: Consequences of germline activation of the RAS/MAPK pathway

Mylène Tajan, Romain Paccoud, Sophie Branka, Thomas Edouard, Armelle Yart
2018 Endocrine reviews  
Indeed, RAS/ MAPK pathway hyperactivation following somatic mutations of genes encoding membrane receptors or actors of the RAS/MAPK pathway has been causally linked to a wide range of cancers, so that  ...  Along with an eightfold increased cancer risk, NS is associated with cancer predisposition, notably childhood cancers ().  ... 
doi:10.1210/er.2017-00232 pmid:29924299 fatcat:c4nsobeibvemlk4qmracibr4u4

Studying a Complex Tumor

Siyuan Zheng, Milan G. Chheda, Roel G.W. Verhaak
2012 The Cancer Journal  
Identification of expression subtypes have resulted in new insights such as the association between genomic abnormalities and expression signatures.  ...  Glioblastoma multiforme (GBM) is a histopathologically heterogeneous disease with few treatment options.  ...  The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Cancer Institute or the National Institutes of Health.  ... 
doi:10.1097/ppo.0b013e3182431c57 pmid:22290264 pmcid:PMC3342695 fatcat:x5hhc3jphnenzatky23pz2cxt4

Identifying Discriminative Biological Function Features and Rules for Cancer-Related Long Non-coding RNAs

Liucun Zhu, Xin Yang, Rui Zhu, Lei Yu
2020 Frontiers in Genetics  
In this study, we utilized a decision tree (DT), a type of rule learning algorithm, to investigate cancer-related lncRNAs with functional annotation contents [gene ontology (GO) terms and KEGG pathways  ...  The rules provided not only a new tool for identifying cancer-related lncRNAs but also connected the lncRNAs and cancers with the combinations of GO terms.  ...  GO: 2000052, which describes the activation (positive regulation) of the Wnt signaling pathway, could contribute to the identification of cancerrelated lncRNAs.  ... 
doi:10.3389/fgene.2020.598773 pmid:33391350 pmcid:PMC7772407 fatcat:fuorhbtwfvg5dah5mvrqkftnyi

Biomarker Identification through Multiomics Data Analysis of Prostate Cancer Prognostication Using a Deep Learning Model and Similarity Network Fusion

Tzu-Hao Wang, Cheng-Yang Lee, Tzong-Yi Lee, Hsien-Da Huang, Justin Bo-Kai Hsu, Tzu-Hao Chang
2021 Cancers  
This study helps us to understand the etiology and pathways of PRAD and further benefits both patients and physicians with potential prognostic biomarkers when making clinical decisions after surgical  ...  Additionally, when evaluating the selected multiomics biomarkers with clinical information (Gleason score, age, and cancer stage), a high-performance prediction model was generated with C-index = 0.713  ...  DL, deep learning; SE, standard error.  ... 
doi:10.3390/cancers13112528 pmid:34064004 fatcat:pf4pldbcarcr7bzc5hwzpvlvbe

Precision and Predictive Medicine in Urothelial Cancer: Are We Making Progress?

Joaquim Bellmunt, Anna Orsola, Guru Sonpavde
2015 European Urology  
Conflicts of interest: Guru Sonpavde has received research support from Onyx, Bayer, and Boehringer-Ingelheim, and is an advisory board member or consultant for Merck, Genentech, Sanofi, and Bayer.  ...  From TCGA we have learned that bladder cancer is a molecularly heterogeneous disease with a multitude of genomic changes affecting many signaling pathways [2] .  ...  The concept of targeting selected patients has also been supported by deep responses when targeting the FGFR pathway with pan-FGFR tyrosine kinase inhibitors in patients bearing tumors with FGFR3 mutations  ... 
doi:10.1016/j.eururo.2015.04.025 pmid:25935702 fatcat:ctdnr3w4r5gkxlbcwyft5di7yq

The Revolutionizing Impact of Artificial Intelligence on Breast Cancer Management

Parvin Akbari, Pegah Gavidel, Mossa Gardaneh
2019 Archives of Breast Cancer  
Deep learning is a branch of ML based on learning data representations, as opposed to task-1 specific algorithms.  ...  Bioinformatics, drug design, and medical image analysis are some of the biomedical applications of deep learning.  ...  Machine Learning Detects Pan-cancer Ras Pathway Activation in The C //] 7. Zinn PO, Singh SK, Kotrotsou A, Hassan I, Thomas G, et al.  ... 
doi:10.32768/abc.201961-3 fatcat:nc6j7d26fnbq3k5w4nm2pku7o4

Synthetic Lethality in Cancer Therapeutics

Roderick L. Beijersbergen, Lodewyk F.A. Wessels, René Bernards
2017 Annual Review of Cancer Biology  
Treatment with targeted drugs has primarily focused on the genes and pathways that are mutated in cancer, which severely limits the repertoire of drug targets.  ...  Synthetic lethality exploits the notion that the presence of a mutation in a cancer gene is often associated with a new vulnerability that can be targeted therapeutically, thus greatly expanding the arsenal  ...  The work of the authors was supported by grants from the Dutch Cancer Society (KWF), the Netherlands Organization for Scientific Research (NWO) through the Center for Cancer Genomics, and the European  ... 
doi:10.1146/annurev-cancerbio-042016-073434 fatcat:ljsesel32nh6npuarjo7nrig2e

EGFs and ERBBs—Brief history and prospects

David F. Stern
2010 Seminars in Cell and Developmental Biology  
The biology and pathogenesis of this system, and its importance for fundamental research in cancer biology is reviewed.  ...  These growth factors and receptors are important drivers in human cancers, and they are the targets for several effective anti-cancer therapies in clinical use.  ...  Acknowledgments This work was supported by USPHS grant R01CA45708 from the National Cancer Institute.  ... 
doi:10.1016/j.semcdb.2010.10.006 pmid:20970513 pmcid:PMC2992880 fatcat:dq2wjvpa2bb2zmjflcnfc3krv4
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