Evaluation of Tumor Response to Adjuvant Treatments using an Ex Vivo Culture of Breast Carcinoma Spheroids in a Microfluidic Device

Abstract Purpose Breast cancer is the leading cause of cancer-related death among women worldwide. Conventional chemotherapy is considered a clinical state of the art treatment; however, resistance or recurrence occurs among a considerable portion of these patients. Besides understanding the genomic alterations pattern of tumor cells and their association with drug resistance or response, the development of a reliable tumor models that reflect the major cellular and molecular features of tumors may aid with screening of candidate drugs and identification of appropriate treatment regimens. Here, we developed a simple and low-cost tumor model of breast cancer to screen library of chemotherapy agents in a pre-clinical setting. Methods we generated and cultured ex-vivo 3D culture of patient-derived tumor spheroids from both pre-treated primary and metastatic tumors using a partial digestion approach in a microfluidic device. We assessed chemotherapy response of the seven patient-derived breast tumor spheroids and expanded evaluation of drug sensitivity through molecular analysis of a small panel of genes. Results We observed various chemotherapy responses across primary and metastasis tumor samples. Interestingly, we demonstrated response to paclitaxel and doxorubicin and resistance to cisplatin in 2/3 metastatic tumor samples while most of the primary tumor were responsive to chemotherapy. Additionally, the expression of PIK3CA and loss of PTEN were associated to treatment resistance. Conclusion Our study suggests potential application of microfluidic-based cell culture technology coupled with patient derived tumor spheroids in prediction of treatment response in a personalized manner.