ABSTRACT
Current standard cancer therapies (chemotherapy and radiation) often cause serious adverse off-target effects. Drug design strategies are therefore being developed that will more precisely target cancer cells for destruction while leaving surrounding normal cells relatively unaffected. Telomerase, widely expressed in most human cancers but almost undetectable in normal somatic cells, provides an exciting drug target. This review focuses on recent pharmacogenomic approaches to telomerase inhibition. Antisense oligonucleotides, RNA interference, ribozymes, mutant expression, and the exploitation of differential telomerase expression as a strategy for targeted oncolysis are discussed here in the context of cancer therapeutics. Reports of synergism between telomerase inhibitors and traditional cancer therapeutic agents are also analyzed.
Subject(s)
Enzyme Inhibitors/therapeutic use , Neoplasms/drug therapy , Oligonucleotides, Antisense/therapeutic use , RNA, Antisense/therapeutic use , Telomerase/antagonists & inhibitors , Drug Design , Enzyme Inhibitors/pharmacology , Humans , Neoplasms/enzymology , Neoplasms/pathology , Oligonucleotides, Antisense/genetics , Oligonucleotides, Antisense/pharmacology , RNA, Antisense/genetics , RNA, Antisense/pharmacology , RNA, Catalytic/genetics , RNA, Catalytic/metabolism , RNA, Untranslated/genetics , RNA, Untranslated/metabolism , Telomerase/genetics , Telomerase/metabolismABSTRACT
Acute rupture of a renal artery aneurysm is more likely to occur during pregnancy and when it does there is an associated high mortality for the mother and child. Increased blood flow and intra-abdominal pressure, and vascular changes secondary to increased steroid production are postulated as contributory to the increased risk of rupture during pregnancy. When a renal artery aneurysm is discovered in a woman of childbearing age surgical treatment, preferably primary repair, is indicated to prevent subsequent rupture during pregnancy. We report on a mother and child who survived acute rupture of a renal artery aneurysm following treatment by primary repair.
