The efficacy of PI3Kγ and EGFR inhibitors on the suppression of the characteristics of cancer stem cells

Cancer stem cells (CSCs) are capable of continuous proliferation, self-renewal and are proposed to play significant roles in oncogenesis, tumor growth, metastasis and cancer recurrence. We have established a model of CSCs that was originally developed from mouse induced pluripotent stem cells (miPSCs) by proposing miPSCs to the conditioned medium (CM) of cancer derived cells, which is a mimic of carcinoma microenvironment. Further research found that not only PI3K-Akt but also EGFR signaling pathway was activated during converting miPSCs into CSCs. In this study, we tried to observe both of PI3K gamma inhibitor Eganelisib and EGFR inhibitor Gefitinib antitumor effects on the models of CSCs derived from miPSCs (miPS-CSC) in vitro and in vivo. As the results, targeting these two pathways exhibited significant inhibition of cell proliferation, self-renewal, migration and invasion abilities in vitro. Both Eganelisib and Gefitinib showed antitumor effects in vivo while Eganelisib displayed more significant therapeutic efficacy and less side effects than Gefitinib on all miPS-CSC models. Thus, these data suggest that the inhibitiors of PI3K and EGFR, especially PI3K gamma, might be a promising therapeutic strategy against CSCs defeating cancer in the near future.

Automated summary

This study established a model of cancer stem cells (CSCs) derived from mouse induced pluripotent stem cells (miPSCs) and found that the activation of PI3K-Akt and EGFR signaling pathways played significant roles in the process. The inhibitors targeting these pathways showed significant anti-tumor effects in vitro and in vivo, with PI3K-gamma inhibitor Eganelisib demonstrating better therapeutic efficacy and fewer side effects.