On August 16, 2022, the Editorial Office of Journal of Cancer Metastasis and Treatment (JCMT) was very honored to interview journal Associate Editor Prof. Ciro Isidoro who is full Professor of General Pathology and Immunology and of Experimental Oncology at the Università del Piemonte Orientale “A. Avogadro”, Novara, Italy.
Prof. Isidoro contributed a high-quality paper “Epigenetic control of autophagy in women’s tumors: role of non-coding RNAs” in 2021 with an excellent Special Issue“Papers from the 3rd International Workshop No-Cancer 2018 ---Understanding Cancer Cell Biology to Improve Diagnosis and Therapy” in 2019. His new Special Issue “Papers from the 6th Cancer World Congress 2022” is also online now. In this interview, Prof. Isidoro shared with us his professional experiences in his research field, the future extensions of his new research, future development and prospects of his new Special Issue.
Here are the details of the interview:
Q1: As an Associate Editor of JCMT, you have published a review in JCMT in 2021 entitle "Epigenetic control of autophagy in women's tumors: role of non-coding RNAs". This paper mainly focuses on the role played by non-coding RNAs-mediated regulation of autophagy in development and progression of cancers in women. After more than a year, could you please give us a brief explanation of the core content of this article? Are there any other latest developments in this regard?
Prof. Isidoro: We are happy to have published this review article in the JCMT. We note with pleasure that it has been well received by the scientific community, with more than 360 downloads within just 18 months. Unfortunately, breast, ovary, endometrial and cervical cancers are still quite frequent among fertile women. So understanding the molecular mechanisms of their pathogenesis is pivotal for improving early diagnosis and therapy. This is a comprehensive review article where the authors illustrate the important role of autophagy in the development of such cancers and how this process is regulated by non-coding RNAs. Autophagy is a catabolic process that largely contributes to cell and tissue homeostasis. When it is dysregulated, it promotes uncontrolled cell proliferation and cell motility, which will consequently lead to the growth and spread of malignant cells. In this article, we examined the epigenetic regulation of this delicate process by non-coding RNAs. It is a new area of cell biology that reveals the complexity of the regulation of gene expression and therefore of cell behavior. These non-coding RNAs, which are classified in small and long dependence on their size, arise from those regions of the DNA that do not transform into proteins and are located either within the genes or in between the genes. Small and long non-coding RNAs have a different mechanism for regulating the effective expression of the genes. The interesting part of the story is that the expression and functioning of these non-coding RNAs depend on environmental factors including the presence/absence of oxygen, growth factors, hormones, drugs, and natural products to a large extent. Thus, non-coding RNAs represent the link between the external stimuli and the intracellular response. It follows that if we learn how to modulate the non-coding RNAs by changing the external environment, we can influence cell behavior. In other words, we may re-educate cancer cells to behave in a good way. In our laboratory, and in collaboration with others (particularly that of Prof. Danny Dhanasekaran), we are learning how natural products can re-educate cancer cell behavior through non-coding RNA-mediated modulation of autophagy.
Q2: You and your team published a research article titled "Resveratrol Contrasts IL-6 pro-growth Effects and promotes Autophagy-mediated Cancer Dormancy in 3D Ovarian Cancer: Role of Mir-1305 and of Its Target ARH-I" on April 25 2022. This paper states the important conclusion: "The possibility of maintaining a permanent cell dormancy in ovarian cancer by the chronic administration of RV should be considered as a therapeutic option to prevent the “awakening” of cancer cells in response to a permissive microenvironment, thus limiting the risk of tumor relapse and metastasis. Hence, we would like to invite you to make a brief statement about the important conclusions of this article and possible future extensions of this research.
Prof. Isidoro: The tumor microenvironment is essentially hypoxic and inflamed, rich of growth factors, motility factors and inflammatory cytokines that promote angiogenesis, cancer growth and invasiveness. It is well known that IL-6, one such inflammatory cytokines, is secreted by cancer associated fibroblasts and is abundant in the tumor microenvironment. We have previously shown that IL-6 promotes the malignant behavior of cancer cells through epigenetic-mediated down-regulation of autophagy, and we have also shown that resveratrol, a natural product present in various fruits and plants, can counteract IL-6 activity and thus rescue autophagy. In this work we have identified a novel oncogenic microRNA (namely miR 1305) that is induced by IL-6 to downregulate autophagy, while resveratrol can counteract the activity of this oncomirna. What we found is interesting is that by doing so, resveratrol maintains the ovarian cancer cells in a dormant state. This exploits a new opportunity for curing cancer. Since we may think to keep dormant for long time of the residual cancer cells after surgery removal or chemotherapy so as to prevent the relapse and the surge of chemoresistant clones.
Q3. Your recent research described the mass versus personalized medicine against COVID‐19 in the “system sciences” era. What do you think of the current situation and future development of personalized medicine against COVID‐19?
Prof. Isidoro: It is a fact that the pandemic COVID-19 has ravaged human lives and it is still affecting our social life as well. Mass vaccination with the current gene-based vaccines has helped to control the worsening of the disease, but unfortunately it has not shown effectiveness in preventing the spreading of the virus. In addition, not all individuals respond to these vaccines, for instance, immunocompromised subjects. Also, there are individuals who develop adverse reactions that cannot not be neglected. It is also a fact that some individuals are more susceptible to the infection, while others develop effective immunization. Therefore, in this article we suggest that a quantitative/analytics data-driven approach should be considered for better profiling the benefit/risk ratio based on genetic determinants, sex, age, ethnic background, and health status of the subjects so that we can effectively improve the preventive/therapeutic efficacy of vaccination. In other words, we propose to exploit the multi-omics technologies for identifying the subjects that effectively could benefit from vaccination with the possibility to predict and thus prevent the possible adverse effect. Thus, we propose that vaccinomic and adversomic should be implemented for a personalized instead of mass vaccination for infectious diseases.
Q4: It is well known that you lead a Molecular Pathology Laboratory. The laboratory was established in the Department of Health Sciences (formerly Dipartimento di Scienze Mediche) at the Università del Piemonte Orientale "Amedeo Avogadro" in Novara in September 1996. The laboratory mainly aims at studying the role and involvement of lysosomal proteolysis in the pathogenesis of diseases. Would you like to share with us any recent projects or latest research progress that you and your team are carrying out?
Prof. Isidoro: As you have anticipated, our research mainly deals with the role of the autophagy-lysosomal proteolysis in the malignant behavior of cancer cells. Let me summarize our most recent findings. We have shown that lysosomal proteolysis by Cathepsin D plays a major role in neuroblastoma cell growth and metastasis. We have also found that the probiotic metabolite butyrate can stop the proliferation of colorectal cancer cells by inducing the autophagy-mediated degradation of beta-catenin (independently of its mutational status). Finally, recently we have described the isolation and functional characterization of novel splicing isoforms of Beclin-1, an oncosuppressor that regulates autophagy.
Q5: Under the joint efforts of you and your team, Cancer World Congress has been successfully held 5 sessions since 2017. We also know that you, as the president, will host the 6th session in Portugal from 28 to 30 September 2022 (http://www.isidorolab.com/public/index.php/2104-2/2022-2/6th-cancer-world-congress-2022/). The topic "Personalized Cancer Diagnosis and Therapy" will also be featured. What motivates you to keep holding this meeting? By taking this opportunity, can you share and publicize this upcoming congress to our audiences?
Prof. Isidoro: This is a series of conferences on cancer that I started to coordinate in 2018, with the conference held in Bologna. In 2019 we held the conference in Prague, and that was the first in partnership with the JCMT for the publication of the proceedings. Due to COVID-19 we had to cancel the conference 2020 in Oslo, while the conference 2021 was held online. Now, we are happy to have the conference 2022 in person in Lisbon. I think there are some features that make this series of conference unique, attractive and very successful. First, it is not sponsored by any association nor by any industry, which means that it is open to all scientists with the only criteria of selection being the expertise in the field and the quality of the work to be presented. Second, at these conferences the participants always enjoy the lectures of prominent keynote and honorary speakers. Just to mention, in Prague 2018 we had the honorary lecture delivered by Thomas Seyfried, an expert in cancer cell metabolism. This year we will have Jacques Pouyssegur and Bonnie F Sloane as honorary speakers. Third, we have a session totally devoted to young investigators with awards for best communication. But the most attractive feature of our conferences is the friendly atmosphere that allows interactions between scientists, and especially helps young researchers to enter in contact with the experts and thus to have opportunities to grow and to perform their future studies in other laboratories abroad.
Q6: Based on this, JCMT is honored to partner with the Cancer World Congress to launch this Special Issue "Papers from the 6th Cancer World Congress 2022". What kind of articles do you plan to focus on through this Special Issue? Here you can share some information with our audience in advance to keep them looking forward to this issue.
Prof. Isidoro: We are very happy of this partnership that allows to publish the proceedings and full articles in the JCMT. I believe that our speakers, and especially the young researchers, will take this opportunity for publishing their most recent findings in the field. Altogether, we will have around 100 lectures and very likely many of these will turn into an original research paper or review article to be submitted to JCMT. With the assistance of the editorial staff, we will monitor the peer review process to secure a rapid decision and help to publish the best papers. Coherent with the theme of the conference, the papers will focus on the relevance of omics technologies for understanding cancer cell biology to improve early diagnosis and to design personalized therapy in cancer.
Biography of the Interviewee
Prof. Ciro Isidoro, DSc, MD, an Associate Editor of the Journal of Cancer Metastasis and Treatment. He is full Professor of General Pathology and Immunology and of Experimental Oncology at the Università del Piemonte Orientale “A. Avogadro”, Novara, Italy, where he leads the Laboratory of Molecular Pathology at the Department of Health Sciences.
Prof. Isidoro is the founding member of International Society of Precision Cancer Medicine and of International Proteolysis Society, the Executive Vice President of International Association of Traditional and Complementary Medicine, and member of Italian Society of Cancerology, European Cancer Society, European Cell Biology Society, among others. Prof. Isidoro's research interests mainly focus on lysosomal proteolysis, pathogenesis of diseases, Cathepsin D, nanobioimaging, autophagy-lysosomal role in cancer.
Thank you for reading and following along. Please also pay more attention to the conference chaired by Prof. Isidoro and the Special Issue of forthcoming articles.
Respectfully Submitted by the Journal Editorial Office
Journal of Cancer Metastasis and Treatment