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Patient-derived organoids may predict clinical response and enable prospective therapeutic selection in pancreatic cancer
Pancreatic ductal adenocarcinoma (PDAC) is characterised by a very poor prognosis. Despite some minor therapeutic advances, median overall survival of patients with metastatic disease ranges from 6 to 11 months. Even for those who undergo potential curative surgery, expected median survival is below 27 months. Current treatment for both localised and metastatic disease is often based on unspecific characteristics, such as performance status and comorbidities. As many patients with PDAC are chemorefractory, there is an unmet clinical need to define responsiveness. Moreover, precision medicine approaches for pancreatic cancer are challenging.
In an article recently published in Cancer Discovery by a multi-institutional group of investigators, a successful methodology to develop pancreatic ductal carcinoma patient-derived organoids is described.1 Seventy-five per cent of attempts to generate organoids did succeed wherever coming from both surgical resection specimens as well as fine needle biopsies. This is an important finding which enables prospective investigation on molecular classification and dynamic resistance to different anticancer agents in pancreatic cancer, where limitations such as amount and quality of available tissue and short survival are very relevant.
Using deep molecular characterisation of the patient-derived organoids’ genome and transcriptome, the expected hallmarks of pancreatic cancer were identified and, interestingly, a very high concordance between the primary tumour and paired organoids was observed. The establishment of such stable models led to the possibility to perform sensitivity test to validate organoids’ response to chemotherapy, comparing the results with the corresponding patient’s clinical effect. Interestingly, it was possible to observe a huge concordance between responses to different agents of organoids and the one obtained by patients. Transcriptional signatures were also derived, mirroring patient outcomes in two separate clinical cohorts. One was made up of patients following adjuvant treatment with gemcitabine and the second was selected in the palliative setting after …
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