Table 2.

Clinical Anticancer Treatments Target FOXO3a through Three Oncogenic Kinases (AKT, IKK, and ERK) and Various Signaling Pathways

Cancer type	Drug or therapy	Protein targeted	AKT, IKK and ERK affected	Signal pathway affected
Breast cancer	Paclitaxel	FOXO3a	AKT	Effected tubulin, Decrease in AKT and increase in JNK activity, leading to FOXO3a activation and induction of Bim [33, 34]
Acute myeloid leukaemia	KP372-1	FOXO3a	AKT	Inhibition of AKT activity, activating FOXO3a and inducing apoptosis [35]
Chronic myeloid leukaemia	Imatinib (STI571 or Glivec)	FOXO3a	AKT and ERK	BCR-ABL inhibition, leading to FOXO3a dephosphorylation and Bim dependent apoptosis; downregulation of ID1 and erythroid differentiation [39, 40]
Osteosarcoma, breast cancer	Ionizing radiation (IR or UV)	FOXO3a	?	Induction of FOXO3a in p53-null cells and enhanced ATM activity [9, 44]
Breast, prostate, kidney, ovarian, non-small-cell lung cancer	Trastuzumab, cetuximab, lapatinib, gefitinib	FOXO3a	AKT and ERK	EGFR blockade; induction of FOXO3a and expression of pro-apoptotic FOXO3a target BNIP3L1 [42]
Leukemia	Doxorubicin	FOXO3a	?	Activation of FOXO3a and MDR1 [38]
Melanoma	Adenovirus-mediated transfer of constitutively active FOXO3A	FOXO3a	?	Activation of FOXO3a and induction of apoptosis [46]
Breast cancer	OSU-03012/ tamoxifen	FOXO3a	AKT	Inhibition of PDK-1/ AKT activity, activating FOXO3a and sensitizing ER-negative breast cancer cells to Tamoxifen [41]
Breast, ovarian cancer	AZD6244	FOXO3a	ERK	Inhibition of ERK activity, activate FOXO3a activity [64]