ArticleCell2018
Chemistry-First Approach for Nomination of Personalized Treatment in Lung Cancer.
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Article in Cell, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 85 papers.
0numbers the graph read from it
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85citing papers in PubMed
5.8field-weighted citation impact, top 3% of its field
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Who cites it
85 citing papers in PubMed, 146 citations in OpenAlex.
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- Deciphering the let-7c-5p/RRM2 axis in lung adenocarcinoma: expression, prognosis, and immune landscape implications.Frontiers in oncology · 2025Article
- SRC kinase drives multidrug resistance induced by KRAS-G12C inhibition.Science advances · 2024Article
- Somatic mutations in autoinflammatory and autoimmune disease.Nature reviews. Rheumatology · 2024Review
- Benzoxazole-derivatives enhance progranulin expression and reverse the aberrant lysosomal proteome caused by GRN haploinsufficiency.Nature communications · 2024Article
25 more citing papers are in PubMed but not listed here.
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Authors and funding
40 authors at 7 institutions in 3 countries.
Elizabeth A McMillanDepartment of Cell Biology, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA.
Myung-Jeom RyuSeverance Biomedical Science Institute, Brain Korea 21 PLUS Project for Medical Science, Yonsei University College of Medicine, Seoul, Korea.
Caroline H DiepDepartment of Cell Biology, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA.
Saurabh MendirattaDepartment of Cell Biology, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA.
Jean R ClemenceauDepartment of Cell Biology, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA.
Rachel M VadenDepartment of Cell Biology, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA.
Ju-Hwa KimSeverance Biomedical Science Institute, Brain Korea 21 PLUS Project for Medical Science, Yonsei University College of Medicine, Seoul, Korea.
Takashi MotoyajiBiomolecular Research Laboratories, Pharmaceutical Research Division, Takeda Pharmaceutical Company, Ltd., Fujisawa, Kanagawa, Japan.
Kyle R CovingtonDepartment of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX 77030, USA.
Michael PeytonHamon Center for Therapeutic Oncology, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA.
Kenneth HuffmanHamon Center for Therapeutic Oncology, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA.
Xiaofeng WuDepartment of Cell Biology, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA.
Luc GirardHamon Center for Therapeutic Oncology, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA.
Yeojin SungSeverance Biomedical Science Institute, Brain Korea 21 PLUS Project for Medical Science, Yonsei University College of Medicine, Seoul, Korea.
Pei-Hsaun ChenChildren's Research Institute, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA.
Prema L MallipeddiDepartment of Biochemistry, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA.
Joo Young LeeSeverance Biomedical Science Institute, Brain Korea 21 PLUS Project for Medical Science, Yonsei University College of Medicine, Seoul, Korea.
Jordan HansonDepartment of Biochemistry, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA.
Sukesh VorugantiDepartment of Biochemistry, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA.
Yunku YuDepartment of Clinical Sciences, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA.
Sunho ParkDepartment of Clinical Sciences, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA.
Jessica SudderthChildren's Research Institute, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA.
Christopher DeSevoDepartment of Cell Biology, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA.
Donna M MuznyDepartment of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX 77030, USA.
HarshaVardhan DoddapaneniDepartment of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX 77030, USA.
Adi GazdarDepartment of Pathology, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA.
Richard A GibbsDepartment of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX 77030, USA.
Tae-Hyun HwangDepartment of Clinical Sciences, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA.
John V HeymachDepartment of Thoracic/Head and Neck Medical Oncology, MD Anderson Cancer Center, Houston, TX 77030, USA.
Ignacio WistubaTranslational Molecular Pathology, MD Anderson Cancer Center, Houston, TX 77030, USA.
Kevin R CoombesDepartment of Biomedical Informatics, The Ohio State University, Columbus, OH 43210, USA.
Noelle S WilliamsDepartment of Biochemistry, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA.
David A WheelerDepartment of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX 77030, USA.
John B MacMillanDepartment of Biochemistry, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA.
Ralph J DeberardinisChildren's Research Institute, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA.
Michael G RothDepartment of Biochemistry, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA.
Bruce A PosnerDepartment of Biochemistry, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA.
John D MinnaHamon Center for Therapeutic Oncology, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA. Electronic address: john.minna@utsouthwestern.edu.
Hyun Seok KimSeverance Biomedical Science Institute, Brain Korea 21 PLUS Project for Medical Science, Yonsei University College of Medicine, Seoul, Korea. Electronic address: hsfkim@yuhs.ac.
Michael A WhiteDepartment of Cell Biology, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA. Electronic address: michael.white@utsouthwestern.edu.
The University of Texas Southwestern Medical Center · USBaylor College of Medicine · USYonsei University · KRSouthwestern Medical Center · USThe University of Texas MD Anderson Cancer Center · USTakeda (Japan) · JPThe Ohio State University · US
Funding
Translational Therapeutics Research Program (TT)P30CA016058 · NCI · OHIO STATE UNIVERSITY · PI Tasleem J Padamsee · 1985 to 2026
$132.3MUNIVERSITY OF TEXAS--SPORE IN LUNG CANCERP50CA070907 · NCI · UT SOUTHWESTERN MEDICAL CENTER · PI GIBBONS, DON LYNN · 1996 to 2024
$57.4MUT Southwestern Medical Center Simmons Comprehensive Cancer CenterP30CA142543 · NCI · UT SOUTHWESTERN MEDICAL CENTER · PI Sandi Leigh Pruitt · 2010 to 2026
$53.7MMetabolic Regulators of Tumor Growth and ProgressionR35CA220449 · NCI · UT SOUTHWESTERN MEDICAL CENTER · PI RALPH J DEBERARDINIS · 2017 to 2026
$9.4MDIVISION OF CELL &MOLECULAR BIOLOGY TRAINING PROGRAMT32GM008203 · NIGMS · UT SOUTHWESTERN MEDICAL CENTER · PI COBB, MELANIE H. · 1987 to 2018
$7.0MCancer Biology Training GrantT32CA124334 · NCI · UT SOUTHWESTERN MEDICAL CENTER · PI SHAY, JERRY WILLIAM · 2007 to 2021
$5.3MLung cancer oncogenotype-selective drug target discoveryU01CA176284 · NCI · UT SOUTHWESTERN MEDICAL CENTER · PI MACMILLAN, JOHN B, MINNA, JOHN D. · 2013 to 2016
$2.8MTargeting Mechanistic Subtypes of Neoplastic DiseaseR35CA197717 · NCI · UT SOUTHWESTERN MEDICAL CENTER · PI WHITE, MICHAEL A. · 2015 to 2015
$725kNCI NIH HHS P30 CA016058NCI NIH HHS P30 CA142543NCI NIH HHS P50 CA070907NCI NIH HHS R35 CA197717NCI NIH HHS R35 CA220449NCI NIH HHS T32 CA124334NCI NIH HHS U01 CA176284NIGMS NIH HHS T32 GM008203
Abstract
Diversity in the genetic lesions that cause cancer is extreme. In consequence, a pressing challenge is the development of drugs that target patient-specific disease mechanisms. To address this challenge, we employed a chemistry-first discovery paradigm for de novo identification of druggable targets linked to robust patient selection hypotheses. In particular, a 200,000 compound diversity-oriented chemical library was profiled across a heavily annotated test-bed of >100 cellular models representative of the diverse and characteristic somatic lesions for lung cancer. This approach led to the delineation of 171 chemical-genetic associations, shedding light on the targetability of mechanistic vulnerabilities corresponding to a range of oncogenotypes present in patient populations lacking effective therapy. Chemically addressable addictions to ciliogenesis in TTC21B mutants and GLUT8-dependent serine biosynthesis in KRAS/KEAP1 double mutants are prominent examples. These observations indicate a wealth of actionable opportunities within the complex molecular etiology of cancer.
Indexed as
Carcinoma, Non-Small-Cell LungCell Line, TumorCell ProliferationCytochrome P450 Family 4Drug DiscoveryG1 Phase Cell Cycle CheckpointsGlucocorticoidsGlucose Transport Proteins, FacilitativeHumansKelch-Like ECH-Associated Protein 1Lung NeoplasmsMicrotubule-Associated ProteinsMutationNF-E2-Related Factor 2Proto-Oncogene Proteins p21(ras)Receptor, Notch2CYP4F11 protein, humanCytochrome P450 Family 4GlucocorticoidsGlucose Transport Proteins, FacilitativeKEAP1 protein, humanKelch-Like ECH-Associated Protein 1KRAS protein, humanMicrotubule-Associated ProteinsNFE2L2 protein, humanNF-E2-Related Factor 2NOTCH2 protein, humanNR3C1 protein, humanProto-Oncogene Proteins p21(ras)Receptor, Notch2Receptors, GlucocorticoidRNA, Small InterferingSLC2A8 protein, humanSmall Molecule LibrariesTTC21B protein, humancancer target identificationchemical biologyciliogenesisglucocorticoid therapiesKRAS mutantlung cancerNRF2 signalingserine biosynthesis
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