Lawrence Pfeffer, PhD, Muirhead Professor of Pathology and director of the Center for Cancer Research at UTHSC, has identified a pathway that is proving successful in making several anti-cancer drugs work more effectively.
Lawrence Pfeffer, PhD, Muirhead Professor of Pathology and director of the Center for Cancer Research at the University of Tennessee Health Science Center (UTHSC) has identified a pathway that is proving successful in making several anti-cancer drugs work more effectively in cancer cells. His study was published in the journal, Cancer Research, in October.
In his study, Dr. Pfeffer and his UTHSC research team (assistant professors Chuan He Yang, PhD; Meiyun Fan, PhD, and Junming Yue, PhD) learned that a specific member of a class of small, genetic molecules referred to as microRNAs* (miRNAs) regulate the sensitivity of cancer cells to anti-cancer drugs. MiRNAs regulate the expression of genes, and in human cancers, certain miRNAs are over-expressed and may function as oncogenes (genes that contribute to cancer). Dr. Pfeffer found that anti-cancer drugs, including Interferon** (IFN), increase the levels of a specific miRNA called miR-21, which is already at high levels in many cancers. Since IFN is useful for treating some cancers, Dr. Pfeffer became concerned that IFN was not as effective as hoped for treating prevalent cancers such as prostate, brain, skin and breast cancer.
Determined to make IFN and other anti-cancer drugs more effective, Dr. Pfeffer targeted his research on IFN to treat several malignancies, including prostate cancer, the leading cancer in males in Tennessee. He confirmed that in cancers where IFN was ineffective for killing cancer cells, IFN rapidly increased the levels of miR-21. In response, Dr. Pfeffer developed a strategy (infusing a specific virus into the cancer cells) to lower the levels of miR-21. The strategy was a success and proved that IFN is quite effective for killing cancer cells when high levels of this specific miRNA were lowered. In addition, lower miR-21 levels makes more cells sensitive to IFN, as well as to a variety of other anti-cancer agents, such as camptothecin and staurosporine.
Dr. Pfeffer’s study is moving into the next phase of research which will be conducted over the next two to three years. If the researcher continues to find success with his strategy, he will test his discovery in human clinical trials.
The research is partly funded through a $500,000 five-year grant from the National Institutes of Health that is shared between Dr. Pfeffer and Andrew M. Davidoff, MD, chair of Surgery at St. Jude Children’s Research Hospital. Dr. Davidoff is directing the clinical study as it relates to brain cancer, while Dr. Pfeffer is leading the basic science component. Both scientists are in their second year of this study. Additional funding of $80,000 to $100,000 annually derives from the UTHSC Muirhead Endowed Chair of Excellence held by Dr. Pfeffer.
*MicroRNAs — Short, RNA genes in plants and animals that are transcribed from DNA, but not translated into protein. MicroRNAs regulate the expression of genes and are usually 20—25 nucleotides in length (a small fraction of the width of a human hair). Although microRNAs generally act within the cell, recent reports show that microRNAs can also be released into the bloodstream.
**Interferon — A protein which triggers the immune system to eradicate pathogens or tumors.