Dr. Felix Zeppernick is currently a fellow at Johns Hopkins and he is also a resident doctor in the Department of Obstetrics and Gynecology at the University of Aachen, Germany. He has joined the research team at Johns Hopkins to develop an academic career in studying ovarian cancer.
Interview questions about ovarian cancer research done by Dr. Felix Zeppernick:1. When did your interest in ovarian cancer research start?
I became interested in cancer biology when I was a medical student after getting to hear various lectures on the topic. I was fascinated by all the tricks a cancer cell can do to become autonomous in growth and evade human defense mechanisms. While I learned that the treatment of ovarian cancer is still particularly difficult, getting to meet patients and their families as a young physician made me even more interested in the topic.
2. Why are you interested in ovarian cancer research?
Being a member of the treatment team for women with ovarian cancer has taught me to establish extremely strong doctor-patient-relationships. Getting the chance to accompany patients and their families during my residency in Germany sadly included too many instances of cancer recurrence although the women had received the so-called “optimal treatment.” Although many improvements have been made in surgical techniques and treatment, the prognosis for ovarian cancer patients often remains poor as we detect the illness too late and our treatment is not effective enough. I think and hope that there is still a lot that can be achieved on improving our handling of this ‘silent killer’. That includes all levels of detection and prevention as well as more effective and targeted therapy.
3. What are you currently working on?
At Hopkins, I am engaged in two very exciting projects. It has been known for a long time that women who take an oral contraceptive pill and women with a low number of lifetime ovulations (e.g. due to pregnancies and breast-feeding) have a lower risk of developing ovarian cancer. We are trying to improve our understanding for this interrelationship. Also we are trying to find out more about the chances of a new treatment with micro RNA (microRNA34) that has shown promising effects in other types of cancer, such as liver cancer.
4. How does stopping ovulation help prevent damage to the fallopian tube?
The cells of the fallopian tube (that connects ovary and the womb) and the ovarian surface lie close together anatomically. Current research suggests that during and after ovulations certain repair mechanisms as well as inflammatory-like processes take place in the surrounding areas of the ruptured follicles. The follicles contain toxic substance that damages the epithelial cells, especially their DNA, leading to changes in DNA structures that may be related to tumor development. Thus, stopping these processes could help to prevent the development of precursor lesions in ovary and fallopian tubes that may eventually progress to ovarian cancer.
5. Is damage to the fallopian tube linked to the development of ovarian cancer? What are the schools of thought?
Yes, this is the current paradigm. Cancer develops as a result of repeated cycles of tissue damage and repair and this process may allow the cells accumulate more genetic alterations such as mutations that predispose the cells to become cancerous ultimately. Researchers in the ovarian cancer research field have long suspected that this is the case in ovarian cancer. The problem is that the data in the literature are tantalizing at best. Thus, I am very interested in asking this question and prove that damage to DNA in fallopian tube and ovarian epithelial cells is the cause to drive ovarian cancer development.
6. How was the deletion of miRNA34a in the development of ovarian cancer discovered?
MicroRNAs have been shown to be involved in the initiation and progression of several cancer types. Studies on ovarian cancer cell lines and tumor tissues could demonstrate that these show reduced levels of miRNA34a compared to normal tissue. Furthermore restoration of miRNA34a function could inhibit typical cancer features like proliferation and invasion.
7. Do you feel the newly developed drug liposomal MRNA34a will be effective in treating low and high grade cancer?
The detection of the micro-RNA-network and the effects of miRNA34a in particularly are still very new. Based on the research that has been done so far there is hope that an add-back therapy might contribute to a better treatment of ovarian cancer. We hope that this will be especially true in the treatment of high grade ovarian cancer.
8. What brings you to this conclusion?
High grade ovarian cancer often show mutations in TP53, a key player of tumor suppressor genes that has many mechanisms of anti-cancer functions. miRNA34a seems to molecularly communicate with p53 and can partly restore its function which raises the hope that this can be an important element in our future treatment strategies.
9. What side effects have you seen with the delivery of this drug?
So far we are not aware of severe side effects in mice of this particular drug. Of course, we have to keep in mind that we still need to gather a lot more information before we make any conclusion. A first clinical Phase 1 trial in humans with liver cancer has been initiated very recently and I am sure that we will learn more about the side effects of this new treatment in the future.