For Immediate Release
Contact: Gina Duclayan, 212-339-0510 or
Sandra Waldman, 212-339-0525
"Trojan Horse" May Offer Prostate Cancer Treatment
Potential safe, effective, non-invasive gene therapy
There may be a safe, effective, non-invasive gene therapy to treat early prostate cancer, reports an article in the June 2000 issue of Population Briefs, based on research from a Population Council scientist. The prospective treatment, which was first described in the 15 April 2000 issue of Cancer Research*, would likely have fewer adverse side effects than experienced with current treatment options. It makes use of a Trojan-horse-like strategy to slip a gene-therapy drug into the nucleus of prostate cancer cells where it can turn off a critical cancer gene.
Patricia L. Morris, of the Council's Center for Biomedical Research, and colleagues linked an anti-gene drug, known as a PNA, to a male steroid hormone. PNAs (peptide nucleic acids) are synthetic analogues of the genetic material DNA. A PNA binds to an active gene that has a structure complementary to its own. This action prevents the production of the gene's protein. Morris's colleagues Lidia C. Boffa, of the National Cancer Institute, Italy, and Umberto Benatti, of the University of Genoa, Italy, designed a PNA complementary to a gene that produces a protein, known as MYC. This protein is thought to be involved in the growth and aggressive proliferation of prostate cancers.
PNAs normally have trouble entering cell nuclei. Morris and her team overcame that hurdle by linking the drug to a form of the male steroid hormone testosterone. The testosterone gave the drug a measure of selectivity, as it only entered the nuclei of cells with androgen receptors. (Most early prostate cancers have androgen receptors.)
"The best therapy would target prostate cancer cells specifically, avoiding damage to all healthy cells," says Morris. Early in vitro results suggest that this therapeutic strategy would meet that requirement.
To assess the compound's effectiveness, Morris and her colleagues performed experiments using two types of human prostate cancer cells: ones containing androgen receptors and ones lacking androgen receptors. The researchers found that the compound was abundantly present in the cytoplasm and nuclei of the cells with androgen receptors. The drug, however, was only minimally present in the cytoplasm and wholly absent in the nuclei of the cells deficient in androgen receptors. Moreover, there was a significant and persistent decrease in the growth of cancer cells and production of MYC protein (a 60-70 percent decline), but only in those cells with androgen receptors.
Still, further basic research needs to be done before this treatment can be tested in humans. Morris would like to test the therapeutic effect of the compound against tumors that grow in animals injected with prostate cancer cells. Because it targets androgen receptors, this strategy may also be useful to deliver other drugs, including contraceptives, or PNAs targeted to different genes directly to cells in the male reproductive system. Furthermore, the same technique could be employed to deliver drugs to cells in the female reproductive system, by linking PNAs to estrogen rather than testosterone.
The Center for Biomedical Research is one of the world's leading laboratories for contraceptive development and for investigation of the male reproductive system.
* "Dihydrotestosterone as a Selective Cellular/Nuclear Localization Vector for Anti-Gene Peptide Nucleic Acid in Prostate Carcinoma Cells"
Lidia C. Boffa, National Cancer Institute, Genoa, Italy; Sonia Scarfi, University of Genoa, Italy; Maria Rita Mariani, National Cancer Institute, Genoa, Italy; Gianluca Damonte, University of Genoa, Italy; Vincent G. Allfrey, The Rockefeller University, New York, NY; Umberto Benatti, University of Genoa, Italy; and Patricia L. Morris, Center for Biomedical Research, Population Council.
To request a copy of the Population Briefs article or a reprint of the study that appeared in Cancer Research, please contact: Sandra Waldman 212/339-0525 or Gina Duclayan 212/339-0510; or send an e-mail message to: [email protected]
To view a summary of the research undertaken in the laboratory of Patricia Morris go to:
http://www.popcouncil.org/biomed/patmorris.html
To view a report about the Cell Culture Facility at CBR go to:
http://www.popcouncil.org/biomed/cellculturefacility.html
# # #
The Population Council is an international, nonprofit, nongovernmental institution that seeks to improve the wellbeing and reproductive health of current and future generations around the world and to help achieve a humane, equitable, and sustainable balance between people and resources. The Council conducts biomedical, social science, and public health research and helps build research capacities in developing countries. Established in 1952, the Council is governed by an international board of trustees. Its New York headquarters supports a global network of regional and country offices.
RSS