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Nat Commun. 2017 Sep 5;8(1):435. doi: 10.1038/s41467-017-00451-5.

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

Author information

1
Genome Institute of Singapore, A*STAR, Cancer Therapeutics & Stratified Oncology, PerkinElmer-GIS Centre for Precision Oncology, 60 Biopolis Street, #02-01 Genome, Singapore, 138672, Singapore.
2
National Cancer Centre Singapore, Cancer Therapeutics Research Laboratory, 11 Hospital Drive, Singapore, 169610, Singapore.
3
Department of Anatomical Pathology, Singapore General Hospital, Outram Road, Singapore, 169608, Singapore.
4
Biological Resource Centre (BRC), A*STAR, 20 Biopolis Way, #07-01 Centros, Singapore, 138668, Singapore.
5
National Cancer Centre Singapore, Cancer Therapeutics Research Laboratory, 11 Hospital Drive, Singapore, 169610, Singapore. gopaliyer@nccs.com.sg.
6
Genome Institute of Singapore, A*STAR, Cancer Therapeutics & Stratified Oncology, PerkinElmer-GIS Centre for Precision Oncology, 60 Biopolis Street, #02-01 Genome, Singapore, 138672, Singapore. dasguptar@gis.a-star.edu.sg.

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.Treatment response in patient-derived models may serve as a biomarker for response in the clinic. Here, the authors use paired patient-derived mouse xenografts and patient-derived primary culture models from head and neck squamous cell carcinomas, including metastasis, as models for high-throughput screening of anti-cancer drugs.

TRIAL REGISTRATION:

ClinicalTrials.gov NCT02806388.

PMID:
28874669
PMCID:
PMC5585361
DOI:
10.1038/s41467-017-00451-5
[Indexed for MEDLINE]
Free PMC Article

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