Core Viewpoint - The article discusses a recent study that highlights the role of fetal-like transcription programs in promoting phenotypic plasticity in colorectal cancer, which is crucial for cancer progression, metastasis, and treatment resistance [2][3]. Group 1: Research Development - A patient-derived organoid model (CiPDO) was developed to capture the fetal-like plasticity state in colorectal cancer [4]. - The CiPDO system was cultivated under specific conditions using EGF, CHIR99021, LDN-214117, and FGF2, allowing for long-term expansion of colorectal cancer cells while retaining fetal-like characteristics [7]. Group 2: Key Findings - The research identified an oncofetal state (OnFS) enriched in advanced tumors, associated with key plasticity features including epithelial-mesenchymal transition, increased metastasis, and enhanced treatment resistance [8]. - Mechanistically, the FGF2-AP-1 signaling pathway was shown to maintain the OnFS program and related phenotypic plasticity in colorectal cancer [9]. Group 3: Implications - The patient-derived organoid model provides a powerful platform for studying the fetal-like characteristics of cancer cells and their roles in tumor progression and treatment resistance in colorectal cancer [11].