Preclinical investigation of patient- derived cervical cancer organoids for precision medicine

Abstract

Objective: Advanced cer vical cancer is still difficult to treat and in the case of recurrentcancer, it is desirable to utilize personalized treatment rather than uniform treatmentbecause the type of recurrence is different for each individual. Therefore, this studyaimed to establish a patient-derived organoid (PDO) platform to determine the effects ofchemotherapy, radiation therapy, and targeted therapy in cer vical cancer.

Methods: We established organoids from 4 patients with various types of cer vical cancer. Thehistopathological and gene profiles of these organoid models were compared to determinetheir characteristics and the maintenance of the patient phenotype. Each type of organoid wasalso subjected to anticancer drug screening and radiation therapy to evaluate its sensitivity.

Results: We established PDOs to recapitulate the main elements of the original patienttumors, including the DNA copy number and mutational profile. We selected 7 drugsthat showed growth inhibition in cer vical cancer organoids out of 171 using an Food andDrug Administration -approved drug librar y. Moreover, adenocarcinoma and large-cellneuroendocrine carcinoma showed resistance to radiation therapy. whereas squamous cellcarcinoma and villoglandular carcinoma showed a significant response to radiotherapy.

Conclusion: Our results showed that patient-derived cer vical cancer organoids can be usedas a platform for drug and radiation sensitivity testing. These findings suggest that patient-derived cer vical cancer organoids could be used as a personalized medicine platform and mayprovide the best treatment options for patients with various subtypes of cer vical cancer.