As shown in Fig. 5B, PX866 increased the numbers of HNSCC Sphes, which is consistent with the result of genetic inhibition of PI3K pathway in Figs 3 and 4, suggesting that inhibition of PI3K pathway may elicit a feedback mechanism of increasing RTKs to maintain CSC property in compensation. Here, PIK3CA is linked to head and neck squamous cell carcinoma.