Phenotype-driven precision oncology as a guide for clinical decisions one patient at a time

被引：68

作者：

Chia, Shumei ^{[1
]}

Low, Joo-Leng ^{[1
]}

Zhang, Xiaoqian ^{[1
]}

Kwang, Xue-Lin ^{[2
]}

Chong, Fui-Teen ^{[2
]}

Sharma, Ankur ^{[1
]}

Bertrand, Denis ^{[1
]}

Toh, Shen Yon ^{[2
]}

Leong, Hui-Sun ^{[2
]}

Thangavelu, Matan T. ^{[1
]}

Hwang, Jacqueline S. G. ^{[3
]}

Lim, Kok-Hing ^{[3
]}

Skanthakumar, Thakshayeni ^{[2
]}

Tan, Hiang-Khoon ^{[3
]}

Su, Yan ^{[1
]}

Choo, Siang Hui ^{[1
]}

Hentze, Hannes ^{[4
]}

Tan, Iain B. H. ^{[1
,2
]}

Lezhava, Alexander ^{[1
]}

Tan, Patrick ^{[1
]}

Tan, Daniel S. W. ^{[2
]}

Periyasamy, Giridharan ^{[1
]}

Koh, Judice L. Y. ^{[1
]}

Iyer, N. Gopalakrishna ^{[2
]}

DasGupta, Ramanuj ^{[1
]}

机构：

[1] ASTAR, Genome Inst Singapore, PerkinElmer GIS Ctr Precis Oncol, Canc Therapeut & Stratified Oncol, 60 Biopolis St,02-01 Genome, Singapore 138672, Singapore

[2] Natl Canc Ctr Singapore, Canc Therapeut Res Lab, 11 Hosp Dr, Singapore 169610, Singapore

[3] Singapore Gen Hosp, Dept Anat Pathol, Outram Rd, Singapore 169608, Singapore

[4] ASTAR, BRC, 20 Biopolis Way,07-01 Ctr, Singapore 138668, Singapore

来源：

NATURE COMMUNICATIONS | 2017年 / 8卷

基金：

英国医学研究理事会;

关键词：

SQUAMOUS-CELL CARCINOMA; TUMOR XENOGRAFTS; CANCER; RESISTANCE; MUTATIONS; MODELS; HETEROGENEITY; FRAMEWORK; BIOBANK; COMPLEX;

D O I：

10.1038/s41467-017-00451-5

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

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 similar to 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.

引用

页数：12

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