Today, we’re presenting a slightly different article than usual on colorectal cancer and its diagnostic innovations. Dr. Federico Sebastiani, founder of Science4Life, interviewed one of our collaborators, Dr. Patrizia Zavattari, who informed us on all the latest news on this particular cancer, of which unfortunately there is still no effective diagnostic test — but on which great progress is being made. This is a unique interview, as it was performed over the phone while Dr. Zavattari was driving, on her way to teach in Nuoro (Sardinia, Italy). We’d like to thank Dr. Zavattari for her availability and, whoever is interested in contacting her, can easily leave a message in the comment section (below).
Dr. Zavattari, please tell us about your background and training.
My training began in Tuscany, where I graduated in Biology (in Pisa), with an experimental degree. Then, I attended a one-year internship in Milan where I began studying autoimmune diseases such as Type 1 Diabetes. I continued studying these diseases in Paris, France and England, and then I moved to Sardinia where autoimmune diseases are quite common. In Cagliari, I started a path of molecular research on Epigenetics, developing various collaborations with groups that study gliomas, hepatocarcinomas, gastro intestinal tumors, and chronic lymphatic leukemias.
There’s a lot of talk about diagnostic tests but little on how they develop. Can you share with us your thoughts?
I’d first like to say that diagnostic tests make sense when there is a therapy that can actually help the patient. Let me give you an example that happened to me personally: I was studying Type 1 Diabetes and I happened to identify people who would develop the disease, but since there was no effective therapy, I didn’t feel like alarming these people for whom it was not certain that they’d get sick — but there was only a certain probability. They would be alarmed without being able to receive any help, and perhaps needlessly, because it was not certain that Diabetes would result.
Are you involved in any research that could potentially lead to the development of a diagnostic test? How did the project come about?
The project to study early epigenetic changes in colorectal cancer first began in 2012. My scientific curiosity was piqued, and I wanted to understand why these early changes led the cell to tumor.
But why study colorectal cancer?
Basically, although it’s one of the most studied tumors (and for which there are effective therapies), it’s also one of the most commonly-occurring cancers. The AIOM (Italian Medical Oncology Association) estimates that in both men and women, colorectal cancer is the second most common after prostate and breast cancer, respectively. Unfortunately, there is not yet an early diagnostic test that can be carried out by a Doctor, accompanied by a precise therapy.
For this reason, I undertook an innovative study; namely the study of the epigenetic changes, that in my initial project, had to be detected via a simple blood sample. These changes affect specific chemical groups that constitute a defined methyloma.
Please explain to us what methyloma is and what the benefits of the methyloma test for early detection of colorectal cancer can be.
Methyloma is the (specific) arrangement of methyl groups that are attached to the DNA molecule on a particular basis, cytosine. Methyloma normally has the function of programming the development of a cell, so a change in methyloma leads to a change in both cell and tissue development. Since the first embryonic cells, methyloma intervenes, along with other mechanisms, and allows the differential development of tissues over time. That is to say, it allows us to become who we are — and to go through the various stages of life; from birth to adulthood, and with all the changes we all know so well.
In tumor cells, unfortunately, an alteration of methyloma occurs, and this phenomenon occurs very early, as compared to the onset of the tumor. Hence, the importance of detecting alterations in methyloma that behave like you car’s “check engine” light; the light that warns us that something is wrong, just before our car breaks down.
How could research like yours transition into a diagnostic test (and become available in hospitals)?
Our research requires the support of a patent, in order to protect this innovation, and to be developed into a diagnostic kit. For this reason, I filed a patent on the alterations I had found, common across cancers and adenomas of the rectum colon. These alterations could be used in a diagnostic and prognostic kit for these diseases. The further interest and importance of this test lies in the fact that the diagnosis can be made directly on the blood with a simple blood sample or in the stool.
The next step will be to approach a company that is interested in marketing this test. While we’re waiting for this to happen, we’re also moving independently toward developing a system that can detect differences in methyloma in a simple and usable way in hospitals, but also by the patient him-or-herself; a Point of Care, as it’s well explained in another Science4Life article.
This Point of Care could be used by patients with colorectal cancer, both for diagnosis, and for monitoring the course of the disease. The data collected by the diagnostic system could be sent directly to the Doctor, with a system that’s also very well described in your article on Telemedicine.
What would you recommend to a young person who’s starting a scientific career, and would be interested in research but also in its practical applications?
I am a pure researcher and in love with research, but for practical reasons I’ve oriented my research toward diagnostic applications. Therefore, I suggest to find a laboratory that has these characteristics, and I’m always well-disposed to collaborations, and to the evaluation of young talents who want to undertake a PhD path. For example, I have a PhD student at Texas University and another one at Adelaide — who are both involved in very interesting cutting-edge studies.
In this video, you can hear (from the speakerphone of Dr. Zavattari) the latest insights on methyloma studies, as applied to chronic lymphatic leukemia.
This post is also available in: Italiano