Method for inhibiting cancer development by fatty acid synthase inhibitors
A method for inhibiting or preventing cancer development by the administration of fatty acid synthase (FAS) inhibitors. In particular, the present invention prohibits or delays the development of invasive cancer from pre-malignant (non-invasive) lesions that express FAS. Compositions containing FAS inhibitors also are provided, as well as methods for administering the FAS inhibitors and compositions to patients in need thereof.
1 . A method of inhibiting cancer development comprising the administration to a subject in need thereof of an effective amount of a fatty acid synthase inhibitor.
2 . A method according to claim 1 wherein the subject is a mammal.
3 . A method according to claim 1 wherein the subject is a human.
4 . A method according to claim 1 wherein the subject has pre-cancerous lesions.
5 . A method according to claim 5 wherein the pre-cancerous lesions express fatty acid synthase.
6 . A method according to claim 5 wherein the pre-cancerous lesions express the neu protein.
7 . A method according to claim 5 wherein the pre-cancerous lesions express fatty acid synthase and the neu protein.
8 . A method according to claim 5 wherein the pre-cancerous lesions are in a tissue type selected from the group consisting of breast, prostate, colon, lung, stomach, mouth, and bile duct.
9 . A method according to claim 8 wherein the tissue type is breast.
10 . A method according to claim 8 wherein the tissue type is prostate.
11 . A method according to claim 8 wherein the tissue type is colon.
12 . A method according to claim 8 wherein the tissue type is lung.
13 . A method according to claim 8 wherein the tissue type is stomach.
14 . A method according to claim 8 wherein the tissue type is mouth.
15 . A method according to claim 8 wherein the tissue type is bile duct.
16 . A method according to claim 1 wherein the effective amount is in the range from about 60 mg/kg to about 7.5 mg/kg per day.
17 . A method according to claim 1 wherein the fatty acid synthase inhibitor is a compound that directly inhibits the fatty acid synthase enzyme.
18 . A method according to claim 1 wherein the fatty acid synthase inhibitor is a compound having the following formula:
wherein:
R 1 ═H, C 1 -C 20 alkyl, cycloalkyl, alkenyl, aryl, arylalkyl, or alkylaryl, —CH 2 OR 5 , —C(O)R 5 , —CO(O)R 5 , —C(O)NR 5 R 6 , —CH 2 C(O)R 5 , or —CH 2 C(O)NHR 5 , where R 5 and R 6 are each independently H, C 1 -C 10 alkyl, cycloalkyl, alkenyl, aryl, arylalkyl, or alkylaryl, optionally containing one or more halogen atoms.
R 2 ═—OH, —OR 7 , —OCH 2 C(O)R 7 , —OCH 2 C(O)NHR 7 , —OC(O)R 7 , —OC(O)OR 7 , —OC(O)NR 7 R 8 , where R 7 and R 8 are each independently H, C 1 -C 20 alky, cycloalkyl, alkenyl, aryl, arylalkyl, or alkylaryl, and where R 7 and R 8 can each optionally contain halogen atoms;
R 3 and R 4 , the same or different from each other, are C 1 -C 20 alkyl, cycloalkyl, alkenyl, aryl, arylalkyl, or alkylaryl.
19 . A method according to claim 1 wherein the fatty acid synthase inhibitor is a compound having the following formula:
R 9 ═H, or C 1 -C 20 alkyl, cycloalkyl, alkenyl, aryl, arylalkyl, or alkylaryl, ═CHR 11 , —C(O)OR 11 , —C(O)R 11 , —CH 2 C(O)OR 11 , —CH 2 C(O)NHR 11 , where R 11 is H or C 1 -C 10 alkyl, cycloalkyl, or alkenyl;
R 10 ═C 1 -C 20 alkyl, cycloalkyl, alkenyl, aryl, arylalkyl, or alkylaryl;
X═—OR 12 , or —NHR 12 , where R 12 is H, C 1 -C 20 alkyl, cycloalkyl, alkenyl, aryl, arylalkyl, or alkylaryl, the R 12 group optionally containing a carbonyl group, a carboxyl group, a carboxyamide group, an alcohol group, or an ether group, the R 12 group further optionally containing one or more halogen atoms;
with the proviso that when R 9 is ═CH 2 , then X is not —OH.
20 . A method according to claim 1 wherein the fatty acid synthase inhibitor is tetrahydro-3-methylene-2-oxo-5-n-octyl-4-furancarboxylic acid.