In malignant tumors, although FOXOs mainly exert antitumorigenic effects [142], they can also advance tumorigenesis, proliferation and drug resistance in some cases, such as promoting the progression of various sarcomas and maintaining leukemia-initiating cells (LISs), leading to drug resistance following human epidermal growth factor receptor 2 (HER2) inhibition in HER2(+) breast cancer [143]. The gene discussed is ERBB2; the disease is breast cancer.