Predicting clinical response to anticancer drugs using an ex vivo platform that captures tumour heterogeneity.

Nat Commun
Authors
Keywords
Abstract

Predicting clinical response to anticancer drugs remains a major challenge in cancer treatment. Emerging reports indicate that the tumour microenvironment and heterogeneity can limit the predictive power of current biomarker-guided strategies for chemotherapy. Here we report the engineering of personalized tumour ecosystems that contextually conserve the tumour heterogeneity, and phenocopy the tumour microenvironment using tumour explants maintained in defined tumour grade-matched matrix support and autologous patient serum. The functional response of tumour ecosystems, engineered from 109 patients, to anticancer drugs, together with the corresponding clinical outcomes, is used to train a machine learning algorithm; the learned model is then applied to predict the clinical response in an independent validation group of 55 patients, where we achieve 100% sensitivity in predictions while keeping specificity in a desired high range. The tumour ecosystem and algorithm, together termed the CANScript technology, can emerge as a powerful platform for enabling personalized medicine.

Year of Publication
2015
Journal
Nat Commun
Volume
6
Pages
6169
Date Published
2015 Feb 27
ISSN
2041-1723
URL
DOI
10.1038/ncomms7169
PubMed ID
25721094
PubMed Central ID
PMC4351621
Links
Grant list
P50 CA090381 / CA / NCI NIH HHS / United States