As the understanding of the biology of ovarian cancer broadens, there is an increased need to develop treatments that are targeted toward a person's genetic makeup, said a clinician-researcher from Baylor College of Medicine.
"We have not been able to pinpoint exactly what causes ovarian cancer," said Dr. Matthew Anderson, assistant professor of obstetrics and gynecology and a member of the NCI-designated Dan L Duncan Cancer Center at BCM. "However, we do know that the molecular changes in each ovarian cancer are different and each person's response to treatment is unique."
Anderson said a major research goal is to individualize treatments for each woman, so that clinicians are able to more effectively manage or perhaps even cure ovarian cancer.
That's why Anderson and his team, including Dr. Martin Matzuk, professor of pathology at BCM, and Dr. Preethi Gunaratne, assistant professor of pathology at BCM and assistant professor of biochemistry and biology at the University of Houston, are in the process of developing treatments that target the different types of molecular changes that they have identified as playing a role in ovarian cancer development.
Identifying new genetic signatures
Their work focuses on a class of recently discovered small non-coding RNA transcripts in ovarian cancer called microRNAs. MicroRNAs are tiny messenger molecules that are generated by chromosomes that feed back to inhibit the expression of traditional, protein-coding genes. They have become a hot topic in biology because an individual microRNA can target many hundreds of different genes, making them potentially very powerful as therapeutic or diagnostic targets, Anderson said.
"Genes have many signals and rules that turn them on and off," said Anderson. "MicroRNAs are one kind of signal. When these signals do not get turned on or off appropriately, gene expression is altered, causing changes in cell behavior that we now know can lead to cancer."
Using Next Generation Sequencing, Anderson and his colleagues identified a number of microRNAs, including miR-31, involved in ovarian cancer. In the case of miR-31, decreased levels were found in every ovarian cancer studied, potentially altering the expression of more than 2,200 individual gene products.
Their work has now been published in the American Association of Cancer Research journal Cancer Research. Anderson also received a basic science award from the Society of Gynecologic Oncologists for a presentation at its 41st Annual Meeting on Women's Cancer in March 2010.
Anderson and team hypothesize that a treatment targeting this malfunction could be effective against cancers that are shown to lack miR-31.
"In the lab, we have shown that once miR-31 is turned back on, cancer growth stops and the cells die," said Anderson.
Next step in research
The next question is finding out how miR-31 can be administered safely as a treatment in humans, Anderson said. "The process will start using ovarian cancer models and then move to human trials."
Another important question is how to determine which patients are likely to benefit from these treatments.
"Physicians understand that the same drug does not always work for the same problem in all people," said Anderson. "This is particularly true for cancer. Understanding how and when microRNAs stop cancer growth can help to tell us how this new class of targets can be used for different people and diseases."
"In the future, we particularly want to be able to take a tumor and comprehensively profile the genetic changes that are specific to the ovarian cancer for each women so that we can prospectively determine what treatment works best for each person," said Anderson. "We believe that this approach will generate far superior results than the currently 'one-size-fits-all' approach used to treat this disease."
Partnership for Baylor College of Medicine campaign
Anderson, Matzuk and Gunaratne's project was selected as the main fundraising effort for 2010-2011 by the Partnership for Baylor College of Medicine, the college's primary support group.
The group will focus their community advocacy, educational programs and involvement in fundraising activities on the project.
"Translating this finding into a clinical application is critically important," said Anderson. "The Partnership support will help us to advance this process significantly."
About ovarian cancer
Ovarian cancer is the fifth leading cause of cancer death in women.
"This is a terrible disease," said Anderson. "Symptoms are non-specific (abdominal bloating, changes in bowel and bladder habits), and the cancer is often diagnosed in the late stages of the disease."
Treatment usually consists of surgery to remove as much of the cancer from a woman's body as possible followed by a regimen of chemotherapy.
"Recurrence rates for this disease are high," said Anderson. "80 percent of the time, the cancer comes back."
If diagnosed early, the cancer is largely curable, Anderson said, however, there are no effective screening methods or tools to help diagnose early. The average age of women who get the disease is 54.