METscreen: Decision-support tool for metastatic colorectal cancer patients based on organoid drug screening in a clinical research feasibility study.

Abstract

e15582 Background: Cancer patients’ survival is directly related to timely identification of effective systemic oncological treatment capable of avoiding drug-resistant cell subpopulations.Personalizing first line treatment decisions with a functional drug screen may allow clinicians to choose the most effective drug before therapy begins, which has the potential to significantly improve patient outcomes. Patient-derived cancer organoids (PDCOs) can be expanded from tumor biopsies ex vivo and are good representations of a patient’s tumor because they exhibit similar response to drugs. Methods: To obtain ex vivo drug screens that accurately reflect patients’ in vivo drug response, we are conducting a single-center, observational clinical research study to address feasibility and determine best practices. This study, (H-24038460) “Technical development of ex vivo growth of (hepatic) metastases from human colorectal cancer by 3D culture of patient-derived cancer organoids (PDCOs),” explores best practices for transportation, processing, and ex vivo culture of PDCOs from cancerous tissue resections. In this study, cancerous tissue from metastatic colorectal cancer patients is processed to make PDCOs for METscreen, our organoid-based functional drug screen, and tested for drug efficacy: resistance and sensitivity. Patients are grouped based on treatment prior to metastatic resection: (i) FOLFOX-, (ii) FOLFIRI-, (iii) 1st and 2nd line treated, and (iv) treatment naïve. The sensitivity and specificity of the drug screens were calculated for each group under different conditions. Best practices were optimized with the prioritization of (1) the ex vivo functional drug screen’s ability to reflect patient’s resistance to prior treatments, (2) expansion potential of PDCOs, and (3) recovery of live cancer tissue and cells in off-site, out-of-hospital laboratory settings. METscreen is cancer organoid-based and provides direct measurement of organoids’ viability after exposure to a drug panel and related dose response. In addition to standardized viability assays, METscreen uses AI to incorporate a novel modality of live, real-time organoid drug response. Results: We used METscreen to measure drug sensitivity and specificity for (a) cancerous tissue resection, (b) transportation, (c) processing and (d) ex vivo culture of PDCOs prior to METscreen. We optimized practices in a clinical setting that prioritizes METscreen’s ability to reflect patients’ clinically-verified drug resistance. Conclusions: Integrating functional drug screening into the clinical setting is the first step in making personalized cancer medicine a reality for all cancer patients. By identifying the most effective treatments for an individual patient’s tumor before therapy begins, we can improve patient outcomes.