Raul A. Urrutia: Epigenomics – possible hope in early diagnosis of pancreatic cancer
The continuation of the „11th ISABS Conference on Forensic and Anthropologic Genetics and Mayo Clinic Lectures in Individualized Medicine“ (www.isabs.net) organized by the International Society for Applied Biology (ISABS) on Tuesday 18th June 2019, was dedicated to the role of epigenomics in diagnosing and treating some of the most severe diseases in humans, such as pancreatic cancer.
Simply put, epigenomics are based on the study of hereditary variations in gene activity, as opposed to genomics that look at the gene's structure. The ability to modify gene activity through new therapeutic targets and smart drugs opens up by this new epigenetic approach.
On this topic, professor Raul A. Urrutia from the American Medical College of Wisconsin gave his speech on pancreatic cancer on the second day of the 11th SABS conference in Split. So we talked briefly with him.
ISABS: You have been presenting today on pancreatic epigenomics. We know it represents a big health problem.
Urrutia: "Indeed, pancreatic cancer is, by its nature, a very aggressive and deadly disease, and one of the problems is that it rapidly spreads throughout the body and produces numerous metastases, even at an early stage of the disease. Approach to treatment is essentially different in the United States and Europe - European countries first apply surgical treatment, and then chemotherapy (so-called neoadjuvant therapy) is being applied. In the United States, we have shown that the opposite approach, i.e. the use of chemotherapy before surgical treatment, can convert non-operable into operable pancreatic cancer in 90% of cases. This is a tremendous success, as it is one of the most problematic diseases that exist."
ISABS: What's new in the epigenetic approach?
Urrutia: "Although there are numerous types and sub-types of pancreatic cancer, which are of different degrees of aggressiveness, with the classic genomic approach it is impossible to differentiate them. For most of the mutations they carry, apart from BRCA-1, it has been shown that they are not suitable as therapeutic targets. Epigenomics are, therefore, far more important in terms of pancreatic cancer and its heterogeneity. The epigenome proved to be the ultimate effector of genomic mutations, which enabled us, after identifying the first group of epigenetic molecular "machinery", to attempt to target that molecular machinery with the new drugs. This therapeutic approach would be termed "epigenetic therapy" or "chemogenetic therapy", because instead of replacing a "diseased" gene, we can block the entire signal path. For example, today I have presented evidence that it is possible with an epigenomic approach, to translate the most aggressive form of pancreatic cancer into less aggressive. These are the first attempts of epigenetic therapy, so it should be remembered that this is an extremely serious and severe illness with five-year survival rate of less than 10%, despite all the efforts and financial resources invested. But, although we are only at the beginning of research of possible therapeutic use, the results are so far promising."
ISABS: Can epigenomics help earlier pancreatic cancer detection?
Urrutia: „At present, clinical guidelines in the United States are such that every person suffering from pancreatic cancer is eligible for genetic testing. We have just conducted a retrospective study in which we sequenced DNA of 550 patients who were suffering from pancreatic cancer, when we found that as many as 20% of them were carriers of pathogenic mutations on genes associated with the development of diseases that provide predisposition for cancer development. Of course, it is not possible to test and screen the entire general population, but we currently consider a screening, for example, in women with ovarian cancer and BRCA mutations, as it is known that they have predisposition to also develop pancreatic cancer.”
ISABS: Is it possible to talk about sensitivity and reliability of such tests for early diagnostics?
Urrutia: „The only test for the purpose of early diagnostics, which, at this moment, provides some kind of hope is analysis of free circulating tumor DNA, so called “liquid biopsy”, on what we are currently working. However, it should be kept in mind that this is only the beginning, but we are certainly dedicated to fighting pancreatic cancer and believe that we will be more successful in the future.”
Raul A. Urrutia held one in a series of lectures explaining the molecular basis of epigenetic control. Professor Urrutia focused on epigenetic regulation by modifying chromatin complexes. The lecture was divided into two parts, and in the first part he referred to the role of the nucleosome remodulation and pointed out that this part of the regulation was "all about moving". Mobility obtained by remodeling nucleosomes is important for achieving the optimal degree of DNA condensation at any given time. In the second part of the lecture he highlighted the characteristics of the enzyme for chromatographic modification, bearing in mind the labels that construct the epigenetic code, or "It's all about marks." He emphasized that hereditary epigenetic markers make the epigenome, while non-hereditary changes are a part of the chromosome dynamics processes.
„11th ISABS Conference on Forensic and Anthropologic Genetics and Mayo Clinic Lectures in Individualized Medicine“ (www.isabs.net), organized by the International Society for Applied Biological Sciences (ISABS), is held from June 17th to 22nd 2019 in Split, Croatia, and it is one of the most prestigious scientific gatherings this year. The conference will be attended by over 600 participants from 45 countries around the world. The fact that more than a million visitors have visited ISABS official website (www.isabs.net) since the foundation of ISABS, and 6000 scientists and 600 invited lecturers from more than 70 countries participated in these congresses, clearly explains the strength of this Croatian scientific brand, recognized worldwide.