Analysis of chemotherapy sensitivity in human pluripotent stem cells

The study of cancer has benefited from the availability of tumor tissues and the development of cancer cell lines. Nevertheless, the cancer genome complexity and differences between species frequently limit clinical translation. In contrast, human pluripotent stem cells (hPSCs) offer a reliable and efficient platform with the advantage of a normal and uniform genetic background. Resistance to anti-cancer drugs represents a major barrier for an efficient treatment and subjects a significant number of patients to ineffective treatment and to excessive chemotherapy side-effects. To assess the potential of hPSCs as a tool to predict anti-cancer drugs sensitivity, we exposed the cells to 107 different chemotherapies from the Approved Oncology Drugs Set. These drugs target over 20 different pathways and mechanisms affecting malignant processes. As expected, hPSC sensitivity varied between the different groups ranging from low to extreme sensitivity. Significant sensitivity has been observed to the Topoisomerase-inhibitors and the epigenetic inhibitors groups. We then evaluated the predictive power of hPSCs compared to human cancer cell lines (hCCls), obtained from Sanger’s and NCI’s Drug Sensitivity Data. This analysis produced a significant positive correlation between hPSCs and hCCls. This high correlation highlights the usefulness of hPSCs in drug response prediction. In contrast, differences have been identified between hPSCs and hCCls in response to epigenetic and topoisomerase inhibitors, highlighting the unique sensitivity of undifferentiated cells to these substances. Together, our results demonstrate the potential of hPSCs in anti-cancer drug research as well as offer new avenues to the study of hPSC and hCCLs cellular differences.