Farnesyl transferase inhibitors cause enhanced mitotic sensitivity to taxol and epothilones Export

@article{citeulike:4116383, abstract = {An important class of cellular proteins, which includes members of the p21ras family, undergoes posttranslational farnesylation, a modification required for their partition to membranes. Specific farnesyl transferase inhibitors (FTIs) have been developed that selectively inhibit the processing of these proteins. FTIs have been shown to be potent inhibitors of tumor cell growth in cell culture and in murine models and at doses that cause little toxicity to the animal. These data suggest that these drugs might be useful therapeutic agents. We now report that, when FTI is combined with some cytotoxic antineoplastic drugs, the effects on tumor cells are additive. No interference is noted. Furthermore, FTI and agents that prevent microtubule depolymerization, such as taxol or epothilones, act synergistically to inhibit cell growth. FTI causes increased sensitivity to induction of metaphase block by these agents, suggesting that a farnesylated protein may regulate the mitotic check point. The findings imply that FTI may be a useful agent for the treatment of tumors with wild-type that are sensitive to taxanes.}, author = {Moasser, Mark M. and Sepp-Lorenzino, Laura and Kohl, Nancy E. and Oliff, Allen and Balog, Aaron and Su, Dai-Shi and Danishefsky, Samuel J. and Rosen, Neal}, citeulike-article-id = {4116383}, citeulike-linkout-0 = {http://www.pnas.org/content/95/4/1369.full.abstract}, citeulike-linkout-1 = {http://www.pnas.org/content/95/4/1369.full.full.pdf}, citeulike-linkout-2 = {http://view.ncbi.nlm.nih.gov/pubmed/9465021}, citeulike-linkout-3 = {http://www.hubmed.org/display.cgi?uids=9465021}, day = {17}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, keywords = {cancer, drug, fti, taxol}, month = {February}, number = {4}, pages = {1369--1374}, posted-at = {2009-03-01 15:55:17}, priority = {2}, title = {Farnesyl transferase inhibitors cause enhanced mitotic sensitivity to taxol and epothilones}, url = {http://www.pnas.org/content/95/4/1369.full.abstract}, volume = {95}, year = {1998} }

TY - JOUR ID - citeulike:4116383 L3 - citeulike-article-id:4116383 N2 - An important class of cellular proteins, which includes members of the p21ras family, undergoes posttranslational farnesylation, a modification required for their partition to membranes. Specific farnesyl transferase inhibitors (FTIs) have been developed that selectively inhibit the processing of these proteins. FTIs have been shown to be potent inhibitors of tumor cell growth in cell culture and in murine models and at doses that cause little toxicity to the animal. These data suggest that these drugs might be useful therapeutic agents. We now report that, when FTI is combined with some cytotoxic antineoplastic drugs, the effects on tumor cells are additive. No interference is noted. Furthermore, FTI and agents that prevent microtubule depolymerization, such as taxol or epothilones, act synergistically to inhibit cell growth. FTI causes increased sensitivity to induction of metaphase block by these agents, suggesting that a farnesylated protein may regulate the mitotic check point. The findings imply that FTI may be a useful agent for the treatment of tumors with wild-type that are sensitive to taxanes. IS - 4 JF - Proceedings of the National Academy of Sciences of the United States of America EP - 1374 TI - Farnesyl transferase inhibitors cause enhanced mitotic sensitivity to taxol and epothilones VL - 95 SP - 1369 KW - cancer KW - drug KW - fti KW - taxol AU - Moasser, Mark AU - Sepp-Lorenzino, Laura AU - Kohl, Nancy AU - Oliff, Allen AU - Balog, Aaron AU - Su, Dai-Shi AU - Danishefsky, Samuel AU - Rosen, Neal PY - 1998/02/17/ UR - http://www.pnas.org/content/95/4/1369.full.abstract ER -