Modeling cervical cancer heterogeneity using patient-derived organoids for precision treatment development

Background : Cervical cancer encompasses diverse histologic and molecular subtypes, yet robust preclinical models that capture this heterogeneity remain limited. This gap continues to hinder the development of precision treatment strategies. Objectives : To establish and characterize a cervical cancer organoid library that reflects intertumoral heterogeneity and supports drug screening and functional genomic approaches. Methods : Organoids were derived from resected cervical cancer tissue from 15 patients and embedded in Cultrex® to support 3D growth. Early- and late-passage organoids, alongside matched patient tumor tissue, underwent morphological evaluation, immunohistochemical profiling, and whole-exome sequencing. Matched 2D cultures were established to compare genomic features and treatment responses between 2D and 3D systems. Drug sensitivity assays including cisplatin, carboplatin, and antibody-drug conjugates (ADCs) are ongoing. Essential genes and therapeutic vulnerabilities will be identified by CRISPR/Cas screens in selected models. Results : Organoids were successfully established from 40% of tumor samples, representing multiple histologic subtypes. These organoids preserved key morphological features of their corresponding tumors. Early drug response assays revealed heterogeneous sensitivity to platinum-based chemotherapy. Consistency in mutational and copy-number profiles between tumors and organoids at both early and late time points is being evaluated to determine genomic stability. Conclusions : This organoid library provides a patient-relevant platform for studying tumor heterogeneity and therapeutic response. Ongoing genomic profiling combined with functional assays across this organoid library may reveal targetable vulnerabilities and ultimately advance precision medicine for cervical cancer patients.