Lonafarnib for cancer and progeria

Abstract

Introduction: Lonafarnib is a non-peptidomimetic inhibitor of farnesyl transferase, an enzyme responsible for the post-translational lipid modification of a wide variety of cellular proteins that are involved in the pathogenic pathways of various diseases including cancer and progeria. Although extensive clinical research indicates limited activity of lonafarnib in solid tumors, there is recent interest in combinations of farnesyl transferase inhibitors with imatinib or bortezomib in hematological malignancies and to investigate the role of lonafarnib in progeria.

Areas covered: This review examines the in vitro and in vivo pharmacology of lonafarnib and the available clinical data for lonafarnib monotherapy and combination therapy in the treatment of solid and hematological malignancies as well as progeria, using studies identified from the PubMed database supplemented by computerized search of relevant abstracts from major cancer and hematology conferences.

Expert opinion: There is no evidence to support the use of lonafarnib in solid tumors. There is ongoing interest to explore lonafarnib for progeria and to investigate other farnesyl transferase inhibitors for chronic and acute leukemias.

Keywords::

• lonafarnib
• farnesyl transferase
• cancer
• progeria