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Institution: South Australian Health and Medical Institute (SAHMRI) - South Australia, Australia
Peritoneal carcinomatosis from gastrointestinal tumors is a grim prognostic factor, but advancements in cytoreductive surgery, intraperitoneal chemotherapy (HIPEC & PIPAC), and patient-derived organoid culture (PDO) have improved median overall survival by 21-32 months. Patient-derived organoid culture (PDOs) offer a breakthrough in personalized medicine, allowing allowing researchers and clinicians to recapitulate the complexity and heterogeneity of individual tumors in-vitro. Our study aimed to assess the feasibility of using PDO cultures for predicting and guiding targeted drug treatments, advocating for their integration into clinical practice.
Tumours samples were collected from patients prior to receiving HIPEC/PIPAC treatments. PDOs were successfully generated from 24 patient samples (n=39) with a 74% culture success rate. Immunohistochemistry and drug panel testing with various drugs (oxaliplatin, mitomycin, gemcitabine, nab-paclitaxel)were completed within 8-10 weeks. Non-linear regression curve fits were used to generate dose response curves in GraphPad Prism with 95% cell viability used to measure resistance. This resulted in a recommendation for treatment change to treating clinicians for three patients undergoing PIPAC as organoid cultures suggested insensitivity to the first-choice PIPAC chemotherapy.
In this poor prognosis cohort, PDOs may represent a transformative tool in personalised medicine, enabling precise prediction of drug responses and facilitating tailored treatment strategies.
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Authors
Dr Harleen Kaur - , Dr Josephine Wright - , Prof Peter Hewett - , Dr Marcus Troschler - , Dr Christopher Lauder - , Dr Laura Vrbnac - , Dr Timothy Price - , Ms Emma Bradshaw - , A/Prof Susan Woods -