6533b857fe1ef96bd12b3ce6

RESEARCH PRODUCT

In the literature: April 2018

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The most important aim of precision medicine is the selection of the best treatment for each individual patient. To achieve this objective, the analysis of the molecular changes that can occur due to tumour heterogeneity or after anticancer treatment is fundamental. A dynamical study of the disease could lead to the identification of specific targets, which need to be inhibited at time of tumour progression. By using high-throughput sequencing, it is possible to identify a very limited number of somatic mutations that can be exploited for cancer treatment and drug development. However, the ability to predict response to targeted agents needs to be further improved. To do this, parallel studies, in which drug responses in patients are matched to laboratory preclinical models to personalise treatment and understand mechanisms of chemosensitivity, are fundamental. Organoids are 3D cell-culture systems generated from cancer cells obtained from tumour biopsies from patients. Organoids models make the dynamical study of tumours alterations possible. A relevant publication on the capability of patient-derived organoids (PDOs) obtained from patients  with heavily metastatic gastrointestinal tumours in predicting response to treatment was recently reported in Science.1 In this article, a total of 110 fresh biopsies obtained from 71 heavily pretreated patients diagnosed with colorectal, gastric cancer or cholangiocarcinoma, enrolled in four Phase I/II clinical trials, were processed by investigators at the Institute of Cancer Research and Royal Marsden Hospital in London. In several cases, PDOs were established from sequential biopsies from metastatic locations at baseline, at the time of best response and at the time of disease progression. Overall, a 96% overlap in mutational spectrum was observed between PDOs, PDO-derived orthotopic tumours (PDO-xenografts) and their parental biopsies. High concordance was also detected in mutational profile, copy number alterations and transcriptomic profiling. Intratumour heterogeneity was also reproduced. Moreover, PDOs were adopted as drug-screening …