Please use this identifier to cite or link to this item: https://doi.org/10.1038/s41467-017-00451-5
Title: Phenotype-driven precision oncology as a guide for clinical decisions one patient at a time
Authors: Chia, S
Low, J.-L
Zhang, X
Kwang, X.-L
Chong, F.-T
Sharma, A
Bertrand, D
Toh, S.Y
Leong, H.-S
Thangavelu, M.T
Hwang, J.S.G 
Lim, K.-H 
Skanthakumar, T
Tan, H.-K
Su, Y
Hui Choo, S
Hentze, H
Tan, I.B.H 
Lezhava, A
Tan, P 
Tan, D.S.W
Periyasamy, G
Koh, J.L.Y
Gopalakrishna Iyer, N
Dasgupta, R
Keywords: antineoplastic agent
belinostat
biological marker
cisplatin
cytotoxic agent
docetaxol
epithelial cell adhesion molecule
erlotinib
flavopiridol
gefitinib
olaparib
protein tyrosine kinase inhibitor
sepantronium bromide
survivin
transcription factor Yap1
unclassified drug
uvomorulin
cisplatin
phosphoprotein
quinazoline derivative
signal transducing adaptor protein
tumor marker
YAP1 (Yes-associated) protein, human
biomarker
cancer
cells and cell components
genetic analysis
phenotype
survival
tumor
accuracy
animal experiment
animal model
Article
cancer genetics
cancer growth
cancer resistance
cancer survival
case study
cell culture
cell proliferation
cell viability
clinical article
clinical decision making
clinical practice
coculture
disease free survival
drug repositioning
drug substitution
drug withdrawal
epithelial mesenchymal transition
esophageal adenocarcinoma
gene expression
head and neck squamous cell carcinoma
human
IC50
immunohistochemistry
in vitro study
lymph node metastasis
monotherapy
mouth squamous cell carcinoma
nonhuman
overall survival
phenotype
primary culture
protein expression
protein protein interaction
rat
short tandem repeat
treatment indication
treatment response
tumor-related gene
unspecified side effect
upregulation
animal
drug resistance
drug screening
gene expression regulation
genetics
head and neck tumor
mouth tumor
nonobese diabetic mouse
pathology
personalized medicine
phenotype
procedures
squamous cell carcinoma
treatment outcome
tumor cell culture
Adaptor Proteins, Signal Transducing
Animals
Biomarkers, Tumor
Carcinoma, Squamous Cell
Cisplatin
Drug Resistance, Neoplasm
Gene Expression Regulation, Neoplastic
Head and Neck Neoplasms
Humans
Mice, Inbred NOD
Mouth Neoplasms
Phenotype
Phosphoproteins
Precision Medicine
Quinazolines
Treatment Outcome
Tumor Cells, Cultured
Xenograft Model Antitumor Assays
Issue Date: 2017
Publisher: Nature Publishing Group
Citation: Chia, S, Low, J.-L, Zhang, X, Kwang, X.-L, Chong, F.-T, Sharma, A, Bertrand, D, Toh, S.Y, Leong, H.-S, Thangavelu, M.T, Hwang, J.S.G, Lim, K.-H, Skanthakumar, T, Tan, H.-K, Su, Y, Hui Choo, S, Hentze, H, Tan, I.B.H, Lezhava, A, Tan, P, Tan, D.S.W, Periyasamy, G, Koh, J.L.Y, Gopalakrishna Iyer, N, Dasgupta, R (2017). Phenotype-driven precision oncology as a guide for clinical decisions one patient at a time. Nature Communications 8 (1) : 435. ScholarBank@NUS Repository. https://doi.org/10.1038/s41467-017-00451-5
Rights: Attribution 4.0 International
Abstract: Genomics-driven cancer therapeutics has gained prominence in personalized cancer treatment. However, its utility in indications lacking biomarker-driven treatment strategies remains limited. Here we present a "phenotype-driven precision-oncology" approach, based on the notion that biological response to perturbations, chemical or genetic, in ex vivo patient-individualized models can serve as predictive biomarkers for therapeutic response in the clinic. We generated a library of "screenable" patient-derived primary cultures (PDCs) for head and neck squamous cell carcinomas that reproducibly predicted treatment response in matched patient-derived-xenograft models. Importantly, PDCs could guide clinical practice and predict tumour progression in two n = 1 co-clinical trials. Comprehensive "-omics" interrogation of PDCs derived from one of these models revealed YAP1 as a putative biomarker for treatment response and survival in ~24% of oral squamous cell carcinoma. We envision that scaling of the proposed PDC approach could uncover biomarkers for therapeutic stratification and guide real-time therapeutic decisions in the future. © 2017 The Author(s).
Source Title: Nature Communications
URI: https://scholarbank.nus.edu.sg/handle/10635/178584
ISSN: 2041-1723
DOI: 10.1038/s41467-017-00451-5
Rights: Attribution 4.0 International
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