Introduction: RNA and the treatment of human cancer.
Epigenetic events are important in carcinogenesis and for the susceptibility of malignant cells to chemotherapy, and this knowledge has identified a new generation of oncogenes and thereby also a new class of possible therapeutic targets for anticancer treatment. RNA reflects gene expression and can thereby be used for identification of therapeutic targets through global gene expression analysis or siRNA screening. However, molecular events at the RNA level are important regulatory mechanisms (i.e., the small regulatory RNAs) and a level for posttranscriptional modification of proteins through alternative RNA splicing. Recent publications have described RNA repair mechanisms that may be involved in carcinogenesis as well as chemosensitivity of human cancer. Most available clinical studies try to target gene expression and thereby RNA-associated regulatory mechanisms mainly through non-specific targeting of gene expression by histone deacetylase inhibition or demethylating agents, but the use of bcl-2 antisense represents an example of specific therapy. Future RNA-targeting studies have to focus on the development of new therapeutic strategies: (i) new therapeutic agents should possibly be more specifically directed towards the target molecules rather than towards more general molecular mechanisms with effects on a wide range of intracellular regulators; and (ii) drug delivery systems have to be developed so that the treatment can be directed towards the localization of the malignant disease to reduce the risk of serious side effects.
Bruserud
Oystein
O
Division of Haematology, Institute of Medicine and Department of Medicine and The Translational Research Program, University of Bergen, Haukeland University Hospital, N-5021 Bergen, Norway. oystein.bruserud@haukeland.no
D044127:Epigenesis, Genetic; D006801:Humans; D009369:Neoplasms / Q000235:genetics / Q000628:therapy*; D012323:RNA Processing, Post-Transcriptional / Q000235:genetics; D012334:RNA, Neoplasm / Q000235:genetics* / Q000378:metabolism
D012334:RNA, Neoplasm