Table 3.

Summary of the alternative therapeutic agents under preclinical investigation (7, 20, 37–42).

Investigated alternative agent	Mechanism of action	Potential drawbacks	Reference
S1P	Inhibition of sphingomyelinase → reduced hydrolysis of the cell membrane lipids→reduction of the pro-apoptotic molecule ceramide→ limitation of primordial follicles cell death	S1P anti-apoptotic effect may antagonize the cytotoxicity of chemotherapy agents	Morita et al. (37)
Imatinib	Inhibition of c-ABl kinase → apoptotic pathway blockade in primordial follicles	Results not replicated in more recent experiments	Gonfloni et al. (38) Kerr et al. (39)
AS101	Reduced activation of the PI3K/PTEN/Akt pathway→reduced primordial follicle maturation →reduced accelerated maturation and death of quiescent follicles	Not reported—actually it may exert an anti-tumor effect	Eichenauer et al. (20) Carmely et al. (40)
G-CSF	↑neovascularization of the ovarian tissue→ protection from ischemia	Not reported	Skaznik-Wikiel et al. (41)
Tamoxifen	Estrogen antagonist- potentially up-regulates IGF-1→ protection of primordial follicles from oxidative stress	Not reported	Roness et al. (7) Ting et al. (42)

S1P, sphingosine-1-phosphate; AS101, ammonium trichloro(dioxoethylene-o,o′)tellurate; G-CSF, Granulocyte colony-stimulating factor; IGF-1, Insulin-like Growth Factor 1.