Abstract
Farnesyltransferase inhibitors were initially developed as Ras inhibitors as they inhibit the prenylation necessary for Ras activation. It is clear now that their mechanism of action is more complex and probably involves other proteins unrelated to Ras. At least 3 drugs within this family have been investigated in acute myeloid leukemia, myelodysplastic syndromes, and other leukemias. These are tipifarnib (R115777, Zarnestra®), lonafarnib (SCH66336, Sarasar™), and BMS-214662. The first 2 are administered orally, whereas BMS-214662 is given intravenously. These drugs are at different stages of development, and design of treatment schedules and methodology of the available studies are very different. Although most of the information is still preliminary, these agents have demonstrated clear evidence of clinical activity in these diseases and very favorable toxicity profiles. Several studies are still ongoing to better define the efficacy of these agents in the treatment of leukemias, as well as to determine the best schedules, the role of combination with other agents, and the role of these agents in different settings, such as the management of minimal residual disease. It is very possible that these agents will soon find their way to the ranks of established agents for the management of myeloid malignancies.
| Original language | English (US) |
|---|---|
| Pages (from-to) | S30-S35 |
| Journal | Clinical Lymphoma |
| Volume | 4 |
| Issue number | SUPPL. 1 |
| DOIs | |
| State | Published - Aug 2003 |
| Externally published | Yes |
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Keywords
- Acute myeloid lymphoma
- BMS-214662
- Geranylgeranyl transferase
- Lonafarnib
- Prenylation
- Ras pathway
- Tipifarnib
ASJC Scopus subject areas
- Cancer Research
Cite this
Farnesyltransferase inhibitors in acute myeloid leukemia and myelodysplastic syndromes. / Cortes, Jorge.
In: Clinical Lymphoma, Vol. 4, No. SUPPL. 1, 08.2003, p. S30-S35.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Farnesyltransferase inhibitors in acute myeloid leukemia and myelodysplastic syndromes
AU - Cortes, Jorge
PY - 2003/8
Y1 - 2003/8
N2 - Farnesyltransferase inhibitors were initially developed as Ras inhibitors as they inhibit the prenylation necessary for Ras activation. It is clear now that their mechanism of action is more complex and probably involves other proteins unrelated to Ras. At least 3 drugs within this family have been investigated in acute myeloid leukemia, myelodysplastic syndromes, and other leukemias. These are tipifarnib (R115777, Zarnestra®), lonafarnib (SCH66336, Sarasar™), and BMS-214662. The first 2 are administered orally, whereas BMS-214662 is given intravenously. These drugs are at different stages of development, and design of treatment schedules and methodology of the available studies are very different. Although most of the information is still preliminary, these agents have demonstrated clear evidence of clinical activity in these diseases and very favorable toxicity profiles. Several studies are still ongoing to better define the efficacy of these agents in the treatment of leukemias, as well as to determine the best schedules, the role of combination with other agents, and the role of these agents in different settings, such as the management of minimal residual disease. It is very possible that these agents will soon find their way to the ranks of established agents for the management of myeloid malignancies.
AB - Farnesyltransferase inhibitors were initially developed as Ras inhibitors as they inhibit the prenylation necessary for Ras activation. It is clear now that their mechanism of action is more complex and probably involves other proteins unrelated to Ras. At least 3 drugs within this family have been investigated in acute myeloid leukemia, myelodysplastic syndromes, and other leukemias. These are tipifarnib (R115777, Zarnestra®), lonafarnib (SCH66336, Sarasar™), and BMS-214662. The first 2 are administered orally, whereas BMS-214662 is given intravenously. These drugs are at different stages of development, and design of treatment schedules and methodology of the available studies are very different. Although most of the information is still preliminary, these agents have demonstrated clear evidence of clinical activity in these diseases and very favorable toxicity profiles. Several studies are still ongoing to better define the efficacy of these agents in the treatment of leukemias, as well as to determine the best schedules, the role of combination with other agents, and the role of these agents in different settings, such as the management of minimal residual disease. It is very possible that these agents will soon find their way to the ranks of established agents for the management of myeloid malignancies.
KW - Acute myeloid lymphoma
KW - BMS-214662
KW - Geranylgeranyl transferase
KW - Lonafarnib
KW - Prenylation
KW - Ras pathway
KW - Tipifarnib
UR - http://www.scopus.com/inward/record.url?scp=0142061051&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=0142061051&partnerID=8YFLogxK
U2 - 10.3816/CLM.2003.s.006
DO - 10.3816/CLM.2003.s.006
M3 - Article
C2 - 14556673
AN - SCOPUS:0142061051
VL - 4
SP - S30-S35
JO - Clinical Lymphoma, Myeloma and Leukemia
JF - Clinical Lymphoma, Myeloma and Leukemia
SN - 2152-2650
IS - SUPPL. 1
ER -