Methods for inducing tumor regression, inhibiting tumor growth, and inducing apoptosis in breast tumors with geranylgeranyltransferase I inhibitors
View Patent ↗Methods of inducing tumor regression, inhibiting tumor growth, and inducing apoptosis with selective peptidomimetic inhibitors of geranylgeranyltransferase I (GGTase I), are provided. In one aspect, GGTI-2418 and its methylester GGTI-2417, increase levels of the cyclin-dependent kinase (Cdk) inhibitor p27 Kip1 and induce breast tumor regression in vivo. In another aspect, GGTI-2417 inhibits the Cdk2-mediated phosphorylation of p27 Kip1 at Thr187 and accumulates p27 Kip1 in the nucleus.
1. A method of treating breast cancer in a subject in need thereof, comprising:
assaying a breast cancer sample comprising breast cancer cells from the subject for nuclear p27 levels;
comparing the nuclear p27 levels to a control level of nuclear p27;
detecting breast cancer cells in the breast cancer sample having nuclear p27 levels that are below control levels of nuclear p27; and
administering a therapeutically effective amount of GGTI-2418 to the subject.
2. The method of claim 1 , wherein the effective amount is 100 mg/kg/day.
3. The method of claim 1 , wherein the effective amount is 200 mg/kg every third day.
4. The method of claim 1 , wherein the administration is performed by intraperitoneal injection.