Tipifarnib in the treatment of newly diagnosed acute myelogenous leukemia

Judith E Karp1, Jeffrey E Lancet21Division of Hematologic Malignancies, Johns Hopkins Sidney Kimmel Comprehensive Cancer Center, Baltimore, Maryland, USA; 2H. Lee Moffitt Comprehensive Cancer Center, Tampa, Florida, USAAbstract: Farnesyltransferase inhibitors (FTIs) represent a new class of signal t...

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Autores principales:	Judith E Karp, Jeffrey E Lancet
Formato:	article
Lenguaje:	EN
Publicado:	Dove Medical Press 2008
Materias:	Medicine (General) R5-920
Acceso en línea:	https://doaj.org/article/a734bcadd2294080afe883a682fb06c3
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spelling	oai:doaj.org-article:a734bcadd2294080afe883a682fb06c32021-12-02T08:56:17ZTipifarnib in the treatment of newly diagnosed acute myelogenous leukemia1177-54751177-5491https://doaj.org/article/a734bcadd2294080afe883a682fb06c32008-09-01T00:00:00Zhttp://www.dovepress.com/tipifarnib-in-the-treatment-of-newly-diagnosed-acute-myelogenous-leuke-a2298https://doaj.org/toc/1177-5475https://doaj.org/toc/1177-5491Judith E Karp1, Jeffrey E Lancet21Division of Hematologic Malignancies, Johns Hopkins Sidney Kimmel Comprehensive Cancer Center, Baltimore, Maryland, USA; 2H. Lee Moffitt Comprehensive Cancer Center, Tampa, Florida, USAAbstract: Farnesyltransferase inhibitors (FTIs) represent a new class of signal transduction inhibitors that block the processing of cellular polypeptides that have cysteine terminal residues and, by so doing, interdict multiple pathways involved in proliferation and survival of diverse malignant cell types. Tipifarnib is an orally bioavailable, nonpeptidomimetic methylquinolone FTI that has exhibited clinical activity in patients with myeloid malignancies including elderly adults with acute myelogenous leukemia (AML) who are not candidates for traditional cytotoxic chemotherapy, patients with high-risk myelodysplasia, myeloproliferative disorders, and imatinib-resistant chronic myelogenous leukemia. Because of its relatively low toxicity profile, tipifarnib provides an important alternative to traditional cytotoxic approaches for elderly patients who are not likely to tolerate or even benefit from aggressive chemotherapy. In this review, we will focus on the clinical development of tipifarnib for treatment of newly diagnosed AML, both as induction therapy for elderly adults with poor-risk AML and as maintenance therapy following achievement of first complete remission following induction and consolidation therapies for poor-risk AML. As with all other malignancies, the optimal approach is likely to lie in rational combinations of tipifarnib with cytotoxic, biologic and/or immunomodulatory agents with non-cross-resistant mechanisms of action. Gene expression profi ling has identified networks of differentially expressed genes and gene combinations capable of predicting response to single agent tipifarnib. The clinical and correlative laboratory trials in progress and under development will provide the critical foundations for defining the optimal roles of tipifarnib and in patients with AMl and other hematologic malignancies.Keywords: farnesylation, farnesyltransferase inhibitor, acute myelogenous leukemia (AML), signal transduction, gene expression, tipifarnib Judith E KarpJeffrey E LancetDove Medical PressarticleMedicine (General)R5-920ENBiologics: Targets & Therapy, Vol 2008, Iss Issue 3, Pp 491-500 (2008)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine (General) R5-920
spellingShingle	Medicine (General) R5-920 Judith E Karp Jeffrey E Lancet Tipifarnib in the treatment of newly diagnosed acute myelogenous leukemia
description	Judith E Karp1, Jeffrey E Lancet21Division of Hematologic Malignancies, Johns Hopkins Sidney Kimmel Comprehensive Cancer Center, Baltimore, Maryland, USA; 2H. Lee Moffitt Comprehensive Cancer Center, Tampa, Florida, USAAbstract: Farnesyltransferase inhibitors (FTIs) represent a new class of signal transduction inhibitors that block the processing of cellular polypeptides that have cysteine terminal residues and, by so doing, interdict multiple pathways involved in proliferation and survival of diverse malignant cell types. Tipifarnib is an orally bioavailable, nonpeptidomimetic methylquinolone FTI that has exhibited clinical activity in patients with myeloid malignancies including elderly adults with acute myelogenous leukemia (AML) who are not candidates for traditional cytotoxic chemotherapy, patients with high-risk myelodysplasia, myeloproliferative disorders, and imatinib-resistant chronic myelogenous leukemia. Because of its relatively low toxicity profile, tipifarnib provides an important alternative to traditional cytotoxic approaches for elderly patients who are not likely to tolerate or even benefit from aggressive chemotherapy. In this review, we will focus on the clinical development of tipifarnib for treatment of newly diagnosed AML, both as induction therapy for elderly adults with poor-risk AML and as maintenance therapy following achievement of first complete remission following induction and consolidation therapies for poor-risk AML. As with all other malignancies, the optimal approach is likely to lie in rational combinations of tipifarnib with cytotoxic, biologic and/or immunomodulatory agents with non-cross-resistant mechanisms of action. Gene expression profi ling has identified networks of differentially expressed genes and gene combinations capable of predicting response to single agent tipifarnib. The clinical and correlative laboratory trials in progress and under development will provide the critical foundations for defining the optimal roles of tipifarnib and in patients with AMl and other hematologic malignancies.Keywords: farnesylation, farnesyltransferase inhibitor, acute myelogenous leukemia (AML), signal transduction, gene expression, tipifarnib
format	article
author	Judith E Karp Jeffrey E Lancet
author_facet	Judith E Karp Jeffrey E Lancet
author_sort	Judith E Karp
title	Tipifarnib in the treatment of newly diagnosed acute myelogenous leukemia
title_short	Tipifarnib in the treatment of newly diagnosed acute myelogenous leukemia
title_full	Tipifarnib in the treatment of newly diagnosed acute myelogenous leukemia
title_fullStr	Tipifarnib in the treatment of newly diagnosed acute myelogenous leukemia
title_full_unstemmed	Tipifarnib in the treatment of newly diagnosed acute myelogenous leukemia
title_sort	tipifarnib in the treatment of newly diagnosed acute myelogenous leukemia
publisher	Dove Medical Press
publishDate	2008
url	https://doaj.org/article/a734bcadd2294080afe883a682fb06c3
work_keys_str_mv	AT judithekarp tipifarnibinthetreatmentofnewlydiagnosedacutemyelogenousleukemia AT jeffreyelancet tipifarnibinthetreatmentofnewlydiagnosedacutemyelogenousleukemia
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Tipifarnib in the treatment of newly diagnosed acute myelogenous leukemia

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