1. ORGANOID DEVELOPMENT IN COLORECTAL CANCER: NEW MODELS FOR PERSONALIZED MEDICINE

Abstract

Abstract Introduction Despite the great advances in recent decades in identifying mechanisms related to tumor progression and resistance to treatment, there are still no safe and effective therapies to treat colorectal cancer (the most common neoplasm in Spain). Organoid models represent a highly promising tool for studying this pathology since they recapitulate, with great precision, the structure and functionality of the original organ. Methods At our center, we have generated an extensive collection of human intestinal organoids, including rectum and colon, from biopsies of healthy tissue and tumor tissue from 72 colorectal cancer patients. For the generation of these models, two different approaches were employed: 1. Organoid generation from intestinal crypts embedded in extracellular matrix droplets; 2. Air-liquid interface (ALI) culture that allows recreating the native microenvironment of the tumor while excluding endogenous infiltrating immune cell populations. Results These organoid collections have been highly characterized, confirming that they retain the molecular, structural, and functional characteristics of their tissues of origin. We present the different findings and their correlation. Conclusion The technology developed by our research group serves as a tool of great translational value for studying response/resistance mechanisms to current colorectal cancer treatments. Additionally, it serves as a predictive model for drug response, playing a crucial role in defining the efficacy of personalized antineoplastic treatments for each patient and advancing the development of personalized therapies against colorectal cancer.