Grant Details
| Grant Number: | 1R21CA227996-01A1 Interpret this number |
| Primary Investigator: | Cheng, Chao |
| Organization: | Baylor College Of Medicine |
| Project Title: | Computational Identification of New Candidate Drugs for Lung Cancer Treatment |
| Fiscal Year: | 2019 |
Abstract
Project Summary/Abstract Lung cancer is the leading cause and accounts for a quarter of all cancer-associated deaths in the United States. There is a constant and critical need for new therapeutic agents to improve treatment of patients with this disease. However, developing an innovative drug is extremely expensive and time- consuming, taking on average 1.1 billion dollars and 11 years. Drug repurposing analysis, which identifies new diseases or indications of existing drugs, provides an effective solution to this problem. Particularly, in the era of big data, a vast amount of biomedical data have been generated, including different types of genomic data and population-based longitudinal healthcare data. These data provide an excellent opportunity for systematic drug repurposing analysis. The primary goal of this project is to apply computational techniques and statistical methods to utilize large-scale genomic and healthcare data for identifying new candidate drugs to treat lung cancer. Specific Aims: In this project we propose to (1) apply a drug repurposing method called IDEA (Integrative Drug Expression Analysis) developed by our group to systematically predict new candidate drugs for lung cancer by integrating diverse genomic data resources, and (2) apply epidemiological analysis to population-based longitudinal healthcare data to identify commonly used drugs that are associated with mortality decrease in lung cancer. In Aim 1, we will integrate 10 lung cancer gene expression data containing ~2500 tumor samples, clinical information of samples, drug treatment profiles for 20,000 compounds including >1300 FDA-approved drugs, and other genomic data sources. In Aim 2, we will systematically analyze the healthcare data from two nationwide population-based databases: the SEER-Medicare database from the United States and the National Health Insurance Research Database from Taiwan. Significance: This project will combine two complementary drug-repurposing strategies to analyze the two most abundant biomedical data types for systematic drug repurposing analysis in lung cancer. Candidate drugs identified by both genomic-based and healthcare-based analyses are supported by both molecular and epidemiological evidences, and deserve more detailed preclinical and clinical investigation. The resulting frameworks and pipelines can be readily extended to drug repurposing analysis in other cancer types and other human diseases.
Publications
Immune Infiltration in Tumor and Adjacent Non-Neoplastic Regions Codetermines Patient Clinical Outcomes in Early-Stage Lung Cancer.
Authors: Cheng C. , Nguyen T.T. , Tang M. , Wang X. , Jiang C. , Liu Y. , Gorlov I. , Gorlova O. , Iafrate J. , Lanuti M. , et al. .
Source: Journal Of Thoracic Oncology : Official Publication Of The International Association For The Study Of Lung Cancer, 2023 Sep; 18(9), p. 1184-1198.
EPub date: 2023-05-04 00:00:00.0.
PMID: 37146750
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Reduced Racial Disparity as a Result of Survival Improvement in Prostate Cancer.
Authors: Zhang B. , Li J. , Tang M. , Cheng C. .
Source: Cancers, 2023-08-04 00:00:00.0; 15(15), .
EPub date: 2023-08-04 00:00:00.0.
PMID: 37568792
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Mosaic Chromosomal Alterations Are Associated With Increased Lung Cancer Risk: Insight From the INTEGRAL-ILCCO Cohort Analysis.
Authors: Cheng C. , Hong W. , Li Y. , Xiao X. , McKay J. , Han Y. , Byun J. , Peng B. , Albanes D. , Lam S. , et al. .
Source: Journal Of Thoracic Oncology : Official Publication Of The International Association For The Study Of Lung Cancer, 2023 Aug; 18(8), p. 1003-1016.
EPub date: 2023-05-05 00:00:00.0.
PMID: 37150255
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VISTA Targeting of T-cell Quiescence and Myeloid Suppression Overcomes Adaptive Resistance.
Authors: Schaafsma E. , Croteau W. , ElTanbouly M. , Nowak E.C. , Smits N.C. , Deng J. , Sarde A. , Webber C.A. , Rabadi D. , Cheng C. , et al. .
Source: Cancer Immunology Research, 2023-01-03 00:00:00.0; 11(1), p. 38-55.
PMID: 36260656
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Genetic variants associated mRNA stability in lung.
Authors: Li J.R. , Tang M. , Li Y. , Amos C.I. , Cheng C. .
Source: Bmc Genomics, 2022-03-11 00:00:00.0; 23(1), p. 196.
EPub date: 2022-03-11 00:00:00.0.
PMID: 35272635
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Immune infiltration difference between tumor and adjacent normal regions is prognostic for gastric cancer patients.
Authors: Zhang B. , Yao K. , Cheng C. .
Source: Clinical And Translational Discovery, 2022 Mar; 2(1), .
EPub date: 2022-02-20 00:00:00.0.
PMID: 35419569
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A framework to predict the applicability of Oncotype DX, MammaPrint, and E2F4 gene signatures for improving breast cancer prognostic prediction.
Authors: Yao K. , Tong C.Y. , Cheng C. .
Source: Scientific Reports, 2022-02-09 00:00:00.0; 12(1), p. 2211.
EPub date: 2022-02-09 00:00:00.0.
PMID: 35140308
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Predicting clinical outcomes of cancer patients with a p53 deficiency gene signature.
Authors: Schaafsma E. , Takacs E.M. , Kaur S. , Cheng C. , Kurokawa M. .
Source: Scientific Reports, 2022-01-25 00:00:00.0; 12(1), p. 1317.
EPub date: 2022-01-25 00:00:00.0.
PMID: 35079034
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A B-Raf V600E gene signature for melanoma predicts prognosis and reveals sensitivity to targeted therapies.
Authors: Yao K. , Zhou E. , Cheng C. .
Source: Cancer Medicine, 2022-01-19 00:00:00.0; , .
EPub date: 2022-01-19 00:00:00.0.
PMID: 35044091
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A lepidic gene signature predicts patient prognosis and sensitivity to immunotherapy in lung adenocarcinoma.
Authors: Nguyen T.T. , Lee H.S. , Burt B.M. , Wu J. , Zhang J. , Amos C.I. , Cheng C. .
Source: Genome Medicine, 2022-01-12 00:00:00.0; 14(1), p. 5.
EPub date: 2022-01-12 00:00:00.0.
PMID: 35016696
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A network-based integration for understanding racial disparity in prostate cancer.
Authors: Zhang B. , Yao K. , Cheng C. .
Source: Translational Oncology, 2022-01-05 00:00:00.0; 17, p. 101327.
EPub date: 2022-01-05 00:00:00.0.
PMID: 34998235
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Deep Learning Predicts EBV Status in Gastric Cancer Based on Spatial Patterns of Lymphocyte Infiltration.
Authors: Zhang B. , Yao K. , Xu M. , Wu J. , Cheng C. .
Source: Cancers, 2021-11-29 00:00:00.0; 13(23), .
EPub date: 2021-11-29 00:00:00.0.
PMID: 34885112
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Clonal Hematopoiesis Mutations in Patients with Lung Cancer Are Associated with Lung Cancer Risk Factors.
Authors: Hong W. , Li A. , Liu Y. , Xiao X. , Christiani D.C. , Hung R.J. , McKay J. , Field J. , Amos C.I. , Cheng C. .
Source: Cancer Research, 2021-11-23 00:00:00.0; , .
EPub date: 2021-11-23 00:00:00.0.
PMID: 34815255
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Resident memory CD8+ T cells in regional lymph nodes mediate immunity to metastatic melanoma.
Authors: Molodtsov A.K. , Khatwani N. , Vella J.L. , Lewis K.A. , Zhao Y. , Han J. , Sullivan D.E. , Searles T.G. , Preiss N.K. , Shabaneh T.B. , et al. .
Source: Immunity, 2021-09-14 00:00:00.0; 54(9), p. 2117-2132.e7.
PMID: 34525340
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Impact of Oncotype DX testing on ER+ breast cancer treatment and survival in the first decade of use.
Authors: Schaafsma E. , Zhang B. , Schaafsma M. , Tong C.Y. , Zhang L. , Cheng C. .
Source: Breast Cancer Research : Bcr, 2021-07-17 00:00:00.0; 23(1), p. 74.
EPub date: 2021-07-17 00:00:00.0.
PMID: 34274003
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Pan-cancer association of HLA gene expression with cancer prognosis and immunotherapy efficacy.
Authors: Schaafsma E. , Fugle C.M. , Wang X. , Cheng C. .
Source: British Journal Of Cancer, 2021-05-12 00:00:00.0; , .
EPub date: 2021-05-12 00:00:00.0.
PMID: 33981015
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Chr20q amplification defines a distinct molecular subtype of microsatellite stable colorectal cancer.
Authors: Zhang B. , Yao K. , Zhou E. , Zhang L. , Cheng C. .
Source: Cancer Research, 2021-02-22 00:00:00.0; , .
EPub date: 2021-02-22 00:00:00.0.
PMID: 33619118
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B cell infiltration is highly associated with prognosis and an immune-infiltrated tumor microenvironment in neuroblastoma.
Authors: Schaafsma E. , Jiang C. , Cheng C. .
Source: Journal Of Cancer Metastasis And Treatment, 2021; 7(34), .
EPub date: 2021-06-06 00:00:00.0.
PMID: 34458583
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Influence of T Cell-Mediated Immune Surveillance on Somatic Mutation Occurrences in Melanoma.
Authors: Jiang C. , Schaafsma E. , Hong W. , Zhao Y. , Zhu K. , Chao C.C. , Cheng C. .
Source: Frontiers In Immunology, 2021; 12, p. 703821.
EPub date: 2022-01-17 00:00:00.0.
PMID: 35111147
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A TMPRSS2-ERG gene signature predicts prognosis of patients with prostate adenocarcinoma.
Authors: Zhou E. , Zhang B. , Zhu K. , Schaafsma E. , Kumar R.D. , Cheng C. .
Source: Clinical And Translational Medicine, 2020 Dec; 10(8), p. e216.
PMID: 33377652
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MYC activity inference captures diverse mechanisms of aberrant MYC pathway activation in human cancers.
Authors: Schaafsma E. , Zhao Y. , Zhang L. , Li Y. , Cheng C. .
Source: Molecular Cancer Research : Mcr, 2020-11-24 00:00:00.0; , .
EPub date: 2020-11-24 00:00:00.0.
PMID: 33234576
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Gene signature-based prediction of triple-negative breast cancer patient response to Neoadjuvant chemotherapy.
Authors: Zhao Y. , Schaafsma E. , Cheng C. .
Source: Cancer Medicine, 2020 09; 9(17), p. 6281-6295.
EPub date: 2020-07-21 00:00:00.0.
PMID: 32692484
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An EGFR signature predicts cell line and patient sensitivity to multiple tyrosine kinase inhibitors.
Authors: Cheng C. , Zhao Y. , Schaafsma E. , Weng Y.L. , Amos C. .
Source: International Journal Of Cancer, 2020-05-14 00:00:00.0; , .
EPub date: 2020-05-14 00:00:00.0.
PMID: 32406930
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Whole transcriptome signature for prognostic prediction (WTSPP): application of whole transcriptome signature for prognostic prediction in cancer.
Authors: Schaafsma E. , Zhao Y. , Wang Y. , Varn F.S. , Zhu K. , Yang H. , Cheng C. .
Source: Laboratory Investigation; A Journal Of Technical Methods And Pathology, 2020-03-06 00:00:00.0; , .
EPub date: 2020-03-06 00:00:00.0.
PMID: 32144347
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VISTA is a checkpoint regulator for naïve T cell quiescence and peripheral tolerance.
Authors: ElTanbouly M.A. , Zhao Y. , Nowak E. , Li J. , Schaafsma E. , Le Mercier I. , Ceeraz S. , Lines J.L. , Peng C. , Carriere C. , et al. .
Source: Science (new York, N.y.), 2020-01-17 00:00:00.0; 367(6475), .
PMID: 31949051
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Multifactorial deep learning reveals pan-cancer genomic tumor clusters with distinct immunogenomic landscape and response to immunotherapy.
Authors: Xie F. , Zhang J. , Wang J. , Reuben A. , Xu W. , Yi X. , Varn F.S. , Ye Y. , Cheng J. , Yu M. , et al. .
Source: Clinical Cancer Research : An Official Journal Of The American Association For Cancer Research, 2020-01-07 00:00:00.0; , .
EPub date: 2020-01-07 00:00:00.0.
PMID: 31911545
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VISTA Re-programs Macrophage Biology Through the Combined Regulation of Tolerance and Anti-inflammatory Pathways.
Authors: ElTanbouly M.A. , Schaafsma E. , Smits N.C. , Shah P. , Cheng C. , Burns C. , Blazar B.R. , Noelle R.J. , Mabaera R. .
Source: Frontiers In Immunology, 2020; 11, p. 580187.
EPub date: 2020-10-15 00:00:00.0.
PMID: 33178206
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Systematic computational identification of prognostic cytogenetic markers in neuroblastoma.
Authors: Qin C. , He X. , Zhao Y. , Tong C.Y. , Zhu K.Y. , Sun Y. , Cheng C. .
Source: Bmc Medical Genomics, 2019-12-12 00:00:00.0; 12(1), p. 192.
EPub date: 2019-12-12 00:00:00.0.
PMID: 31831008
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CD36-Mediated Metabolic Rewiring of Breast Cancer Cells Promotes Resistance to HER2-Targeted Therapies.
Authors: Feng W.W. , Wilkins O. , Bang S. , Ung M. , Li J. , An J. , Del Genio C. , Canfield K. , DiRenzo J. , Wells W. , et al. .
Source: Cell Reports, 2019-12-10 00:00:00.0; 29(11), p. 3405-3420.e5.
PMID: 31825825
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Computational STAT3 activity inference reveals its roles in the pancreatic tumor microenvironment.
Authors: Schaafsma E. , Yuan Y. , Zhao Y. , Cheng C. .
Source: Scientific Reports, 2019-12-03 00:00:00.0; 9(1), p. 18257.
EPub date: 2019-12-03 00:00:00.0.
PMID: 31796877
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BioMethyl: an R package for biological interpretation of DNA methylation data.
Authors: Wang Y. , Franks J.M. , Whitfield M.L. , Cheng C. .
Source: Bioinformatics (oxford, England), 2019-10-01 00:00:00.0; 35(19), p. 3635-3641.
PMID: 30799505
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Statins associate with improved mortality among patients with certain histological subtypes of lung cancer.
Authors: Ung M.H. , MacKenzie T.A. , Onega T.L. , Amos C.I. , Cheng C. .
Source: Lung Cancer (amsterdam, Netherlands), 2018 12; 126, p. 89-96.
EPub date: 2018-10-25 00:00:00.0.
PMID: 30527197
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