Circulating Tumor Cells Derived from Advanced Hepatocellular Carcinoma Rapidly Develop Resistance to Cytotoxic Chemotherapy.

Abstract

Clinically, some cancer patients develop drug resistance after receiving a few courses of chemotherapy, or even worse, completely lack therapeutic response. Prediction of treatment response before administration is of value to oncologists. This study aimed to evaluate the feasibility of drug sensitivity tests for circulating tumor cells (CTCs) isolated from patients with advanced hepatocellular carcinoma (HCC). CTCs isolated from patients receiving cytotoxic chemotherapy or sorafenib were subjected to drug tests using ex vivo culture. Thirty-one patients with advanced HCC and one with benign lesions were enrolled in the study. After incubation with chemotherapeutic drugs ex vivo, the numbers of CTCs were decreased in 10/12 (83.3%) of treatment-naïve patients (planning to receive the first course of chemotherapy) but increased in all patients (6/6) who had received chemotherapy (p=0.002). The CTC count was negatively correlated with the overall survival of patients (p=0.016). The CTCs of patients who received targeted therapy (n=11), were incubated with sorafenib for sensitivity tests. After comparing the chemotherapy and sorafenib-treated groups, the CTCs in the latter group had a lower probability to develop drug resistance (p=0.031). An ex vivo culture-based drug sensitivity test was developed for CTCs isolated from advanced HCC patients. The drug test found that resistance developed rapidly following cytotoxic chemotherapy, whereas it was rarely observed in patients receiving sorafenib. For patients with advanced HCC who choose to receive chemotherapy, CTC drug sensitivity tests may help predict treatment response.