Dr Antonio Giordano of Sbarro Health Research Organization: 5 Things Everyone Needs To Know About Cancer
An Interview With Savio P. Clemente
Cancer is a treatable disease if caught early. For example, most ovarian cancers are detected at late stage (Stage III or higher) and by this time, the cancer is less sensitive to many of the therapies we have available for this disease. The same for breast cancer. Much work and effort among researchers is dedicated to early detection of cancer.
Cancer is a horrible and terrifying disease. There is so much great information out there, but sometimes it is very difficult to filter out the noise. What causes cancer? Can it be prevented? How do you detect it? What are the odds of survival today? What are the different forms of cancer? What are the best treatments? And what is the best way to support someone impacted by cancer?
In this interview series called, “5 Things Everyone Needs To Know About Cancer” we are talking to experts about cancer such as oncologists, researchers, and medical directors to address these questions. As a part of this interview series, I had the pleasure of interviewing Dr. Antonio Giordano.
Dr. Antonio Giordano is Founder of the Sbarro Health Research Organization at Temple University. SHRO conducts groundbreaking research to diagnose, treat and cure cancer, cardiovascular disease and other chronic illnesses. Dr. Giordano is an internationally recognized expert in cancer research and pathology and has contributed some of the seminal findings which have become the basis for our current understanding of how cancer forms and how we can treat it. Dr. Giordano has published over 600 papers on gene therapy, genetics of cancer and epidemiology.
Thank you so much for joining us in this interview series! Before we dive into the main focus of our interview, our readers would love to “get to know you” a bit better. Can you tell us a bit about your childhood backstory?
I was born in Naples, a wonderful town lying on the Mediterranean Sea under the shadow of the big volcano, Vesuvio. I have always been a creative person with a positive attitude like most of my fellow citizens. From my dad, a renowned scientist, I learned to be curious and started at an early age to get engaged in science. But my great passion was also soccer and I used to escape the family house to go and play with friends, with the complicity of my mom who would throw me the football bag from the balcony.
What or who inspired you to pursue your career? We’d love to hear the story.
I have to give credit to three people who were extremely influential in my formation as a scientist, clinician, and head of an international research organization. First my father Dr. Giovan Giacomo Giordano. My father was a doctor and professor of pathological anatomy at the University of Naples. In the course of his professional career, he became aware of the need to broaden his horizons and to confront other scientific realities. This is how he began to establish scientific collaborations with colleagues from other countries.
Then, when I told him that I was going to become a doctor, despite being a student, he offered me the opportunity to spend my summer vacation in the United States.
At the age of seventeen, I became very passionate about the American reality: I learned the language and after specializing in Pathological Anatomy at the University in Trieste, I moved to the USA for a doctorate. So at an early age, I could not have had a better mentor, who not only instilled in me that scientific curiosity and passion for medicine which every scientist/clinician needs, but a sense of ethical responsibility in science and medicine. For this, the SHRO honors him every year at the annual National Italian American Foundation medical conference, awarding the Giovan Giacomo Giordano Foundation and National Italian American Foundation Award for Ethics and Creativity in Medical Research.
The second person would be Nobel Prize winner Dr. James Watson, director of the prestigious Cold Spring Harbor Laboratory, where I did my postdoctoral work. He is one of the fathers of modern genetics and one of the authors of the discovery of DNA’s double helix. During these years I had to sacrifice a lot, young, meeting my future wife, and in a foreign country. I spent many sleepless nights in the laboratory. I also learned there to gain confidence in what I was doing. I remember how I would question results, asking more in-depth questions of my own research. This is how eventually I discovered the new RB2/p130 gene. These years were not only formative for me as a scientist, but being and succeeding in such a high powered environment, helped springboard my career. I have to admit that since graduating, I have always been very focused on my work and the goals I wanted to achieve.
The third person who played a big role in my success, has to be Mario Sbarro, the head of Sbarro Foods. I went to visit him, explaining my ideas regarding the birth of a scientific research institute. Mr. Sbarro listened to me. We spoke to each other several times, and he decided to help me financially and provide me with a staff of professionals. I have a deep affection for Mario Sbarro and a great gratitude for the trust that he placed in me many years ago. He remains an important person to me and the organization that we have created.
This is not easy work. What is your primary motivation and drive behind the work that you do?
You must have a passion for what you are doing. This was instilled in me at an early age but I feel this is the nature of doing science and most young scientists I see are very passionate about their work and helping others. Second, always keep asking questions and don’t be afraid to venture into new fields. Always know what are the new technologies, innovations and discoveries that are driving your field and the larger scope of biomedicine. And stick to your guns! Believe in what you are doing. Don’t let the critics get to you. In my career there were many examples of this.
First, when I was a postdoctoral fellow, I knew my findings were correct and this led to my discovery of the tumor suppressor RB2/p130. This discovery led to seminal publications in my early career and spring-boarded scientific success for me.
The second time I “stuck to my guns” was in creating the Sbarro Health Research Organization with the support of Mario Sbarro. As a result, I had the privilege to mentor over 1000 young scientists and clinicians, many of whom achieved amazing success in their endeavors. This also gave me the opportunity to help out young budding scientists early in their academic lives, something which is very important for me. I feel there are not many avenues for young people to really succeed so giving them this opportunity is really important for me.
The third moment is when I dedicated myself to communicating about the environmental hazards in the region of my birth, Campania. And although it led to professional awards and recognition, it was more important to me to see this work to its fruition because first, it is the ethical thing to do and second, I could not see people suffer in such a way, especially in my homeland.
Therefore, it is extremely important for young scientists to learn how to communicate their findings. I am very blessed that SHRO affords them that opportunity. Too often now I see other big publication houses sort of close their doors to young investigators and give special treatment to well-connected investigators. Two prominent Nobel Laureates have lamented this recently, accusing many big scientific publications of reserving publication of scientific findings to a select number of preferred institutions and/or investigators. To me this is not only unethical but stymies the future of science by limiting options for young investigators to communicate their findings. Much good science has been wasted by this. In fact, over a decade ago, multiple scientists voiced this concern and ultimately led to the open access movement in scientific publication. This is a time when the leaders in science have to look to the future.
And remember, when you do find that success, become a great mentor to people. This I feel has been my greatest achievement is science.
What are some of the most interesting or exciting projects you are working on now? How do you think that might help people?
We have numerous projects within the Sbarro Health Research Organization in cancer therapy, epigenetics, neurologic diseases, and diabetes but I will summarize a few notable projects. First, we are developing a new class of cell cycle inhibitors based on my previous discoveries, and working with a few clinicians to get these into clinical trials for various cancers, including malignant mesothelioma, a deadly cancer related to asbestos exposure for which at present there is no curative modality. We are also developing gene therapies to reactivate certain tumor suppressor functions in cancer. Third, we are working on establishing the link between diet and cancer, and investigating some of the cancer preventive properties found in certain types of tomato grown in Italy. Lastly, we are understanding the role that virtual reality can have in improving the cancer patient’s wellbeing.
For the benefit of our readers, can you briefly let us know why you are an authority about the topic of Cancer?
Overall, my research is focused in three main areas:
1) Understanding the links between the cell cycle, proliferation and cancer.
2) Determining the cancerous effects of environmental contamination.
3) Researching the association between obesity, diet, and cancer.
In these areas I have over 600 peer reviewed publications and over 20 US patents on cell cycle inhibitors and gene therapies for various tumor types. Specifically, I isolated the tumor suppressor RB2/p130 gene, later showing how the same gene, introduced through a retrovirus in some animal models, is able to reduce the growth of tumors. However, through SHRO, we have increased our research portfolio to include the study of neurologic diseases like Alzheimer’s as well as diabetes. In addition, I have identified the direct link between cell cycle regulation and cancer development. More specifically, I have been able to demonstrate that normal cells become neoplastic when oncogenes interact directly with the cyclins, leading to a deregulation of the cell cycle and, consequently, to the onset of the neoplastic phenotype. Subsequently, I discovered three important “guardians” of the human genome: CDK9, CDK10 and the NSPs (Novel Structure Proteins), a new protein structure with a potential role in the dynamics of the nucleus during cell division. One particular protein, Isoform NSP5a3a, is highly expressed in some tumors and could turn out to be a very useful tumor marker. In recent years I have focused efforts on studying the relationship between cancer and environmental pollution in Campania, linking my career as a researcher to that of a science communicator. I was among the first to report an increased incidence of various types of cancer in populations near illegal toxic waste sites. I published numerous findings on the link between cancer and multiple types of toxins attributed to the landfill waste, reporting high levels of the cancer-causing dioxins in surrounding wildlife and high levels of heavy metals in cancer patients from the region. Not only have we published scientific articles on this subject, but I also committed to making these data known through two books on the subject, “Campania, lterra di veleni” (translated “Campania; Land of Fires”) and “Monnezza di stato” (translated “Government Garbage”) edited by Denaro Libri and Minerva respectively. The former was produced also as a movie. The publications also launched a petition to protect the environment, signed by over 500 researchers and people from various professional sectors. I also promoted numerous non-profit initiatives aimed at safeguarding the environment and human health.
Ok, thank you for all of that. Let’s now shift to the main focus of our interview. Let’s start with some basic definitions so that we are all on the same page. What is exactly cancer?
Cancer is the unregulated and unchecked proliferation of your body’s own cells. This is why cancer is so tricky to treat, unlike an infection which is foreign. You are basically fighting a war against your own cells, although they have become altered to divide over and over again. In addition, you have to try to kill the cancer cells while leaving your healthy cells intact. This is one of the biggest challenges for the oncologist.
What causes cancer?
The simplest answer is that mutations in certain genes in DNA are the earliest event which starts a cell on the pathway to eventually become a cancerous cell. These mutations permanently alter the function of many proteins in the cell, proteins which can regulate the cell proliferation and growth. But over the years we have realized that the development of a tumor that can travel, or metastasize, to other parts of the body, relies on multiple changes occurring within the cell and the surrounding tissues. For instance, years ago we did not understand the role that the immune system has in eliminating cancerous cells, but now we have a whole new class of therapies to help the immune system recognize and destroy those tumor cells.
What is the difference between the different forms of cancer?
This has been a very tough question to answer because we now know, with all our advances in genomics, that each person’s cancer, whether it starts in the colon, or ovary, or in the blood, is unique. Each person’s cancer may have some common mutations with other types of cancer but each person’s individual cancer has their own set of mutations and characteristics, which make this new era of personalized medicine both exciting yet challenging. Because each person’s tumor reacts differently to different drugs because of this diversity between individual tumors. For instance many breast, ovarian, colon, or lymphomas may have mutations in a gene we call “the guardian of the genome”, TP53, but will have numerous other types of mutations which drive each individual tumor’s growth differently, and also the patient’s outcome. Because of this we have, over the years, changed our view to look more precisely at all these genetic differences between tumors, and this has changed how we diagnose, treat, and develop medicine to cure cancer.
I know that the next few questions are huge topics, but we’d love to hear your thoughts regardless. How can cancer be prevented?
The best way to prevent cancer is through lifestyle changes. For instance, we have shown that quitting smoking drastically reduces the chances of developing lung cancer. We also have shown that reducing exposure to asbestos drastically reduces the incidence of mesothelioma. Vaccines against human papillomavirus can help to prevent cervical and other cancers. Now we are investigating the positive effects of a healthy Mediterranean diet on reducing the incidence of other types of cancer.
How can one detect the main forms of cancer?
Over the years, our ability to detect cancer, especially in the early stages when cancer is most treatable, has improved greatly. Imaging techniques have improved and, as a result of the development in genomics and proteomics, we can more accurately diagnose the specific type of cancer and also determine the best treatment option for that patient. We also have developed ways to detect individual cancer cells in blood and urine (we call this liquid biopsy) and this has greatly enhanced our ability to detect certain deadly forms of breast cancer, which are not seen on mammograms. Early detection though is key to best success in treating a patient.
Cancer used to almost be a death sentence, but it seems that it has changed today. What are the odds of surviving cancer today?
Cancer survival rates have gradually and for some cancers, drastically improved over the years. This is a result of better diagnosis where we can catch the tumor at an earlier and more treatable stage. Also our arsenal of therapies have improved greatly, especially in this era of personalized medicine. Some cancers, like pancreatic cancer and certain breast and ovarian cancers still have not seen improvement in survival rates. Researchers are working very hard in these areas.
Can you share some of the new cutting-edge treatments for cancer that have recently emerged? What new cancer treatment innovations are you most excited to see come to fruition in the near future?
In the last 10 years we have developed a completely different way to approach cancer therapy. All of the conventional treatments (Chemo and radiotherapy) were aimed to kill cancer cells targeting their replicative dysfunction. A target which was extremely unspecific, doomed by the rapid occurrence of resistance and unable to spare normal tissues with consequent severe toxicity. At the present, we have started to use our improved knowledge to target tumor cell ability to interact with the host and with the microenvironment and to manage and enforce a tumor specific immune response. We have an expanding arsenal of drugs targeting cancer specific molecular alterations: We have mAbs and small molecules that are able to block surface receptors able to promote cell proliferation, angiogenesis and metastases. Other drugs are able to target and inhibit tumor specific pathways related to mutation/rearrangement in proteins which are able to sustain the neoplastic phenotype.
For what concerns the immuno oncological treatments together with the classic immuno target we have now new biological drugs (mAbs immune check-point inhibitors) able to restore the ability of tumor specific cytotoxic T lymphocytes with consequential long term antitumor control. All these precision medicine approaches allow us to tailor patients’ treatment based on the individual cancer features. Today we are well positioned, owing to the availability of many high-throughput technologies, to identify new drugs at an unprecedented pace. However, we need to insist on the design of independent, academic trials based on strong preclinical studies to allow a successful cost-effective implementation of new strategies in the clinical practice.
Healing usually takes place between doctor visits. What have you found to be most beneficial to assist a patient to heal?
We cannot forget the human within the patient. A complete care including the best palliative, psychological, spiritual and social support are the greatest allies for the specific oncological treatment. An example of this is our work on the use of virtual reality with breast cancer patients. We have much evidence that improving the wellbeing of the patient improves outcomes for this disease.
From your experience, what are a few of the best ways to support a loved one, friend, or colleague who is impacted by cancer?
When someone initially gets a diagnosis of cancer, it is a very stressful period for the individual, and the diagnosis becomes stressful for many of their loved ones. One fear the newly diagnosed have is how do I tell my family, my friends, and this becomes even more stressful for the patient as loved ones react to the news of the diagnosis. The most supportive role a family member can play is to just listen and be understanding of the changes that will occur in their loved ones’ lives as well as their family life. Well-intentioned advice sometimes leads to an even more stressful situation for the affected one. Many patients find patient-support groups useful just for the ability to talk with other people going through their disease. Sbarro works with many patient-advocacy groups and this is a recurring theme. As experts in the cancer field, we also have a duty to provide good information. This was very evident during the start of the COVID-19 pandemic, when little guidance for cancer patients and their oncologists was available. We at Sbarro, together with oncologists worldwide would meet to discuss these issues and eventually, through expert panel discussions, consensus guidelines were formulated for cancer patient care. Patient advocacy groups were very appreciative of this.
What are a few of the biggest misconceptions and myths out there about fighting cancer that you would like to dispel?
First, that cancer is a death sentence. We have made great strides in the diagnosis and treatment of many forms of cancer and cancer survival rates are improving in most of the world. The second is related to the first myth; that basic research does not have much value. All of these improvements in cancer outcomes have been founded on solid, good basic cancer research, and this research should be vigorously funded. There are many brilliant scientists out there, both young and old, working very hard to find cures for this disease.
Thank you so much for all of that. Here is the main question of our interview. Based on your experiences and knowledge, what are your “5 Things Everyone Needs To Know About Cancer? Please share a story or example for each.
1. Cancer is a treatable disease if caught early. For example, most ovarian cancers are detected at late stage (Stage III or higher) and by this time, the cancer is less sensitive to many of the therapies we have available for this disease. The same for breast cancer. Much work and effort among researchers is dedicated to early detection of cancer.
2. Each person’s tumor is different and genetic testing is critical to find the best therapy to suit individual cancer. Precision and personalized medicine has been possible because of the advances we have made in genetic sequencing. In addition, we have been able to find genetic mutations that increase risk of developing cancer, such as in colon, ovarian, and breast cancer. We are now understanding how to take advantage of these mutations to develop therapies for these particular patients.
3. Well funded basic research is the driver of discovery for new cancer therapies. The discoveries of RB2 and the link between cancer and proliferation that I found many years ago have contributed to the development of multiple therapies, some of which are just now finding their successful application into clinical practice. Due to the many fiscal constraints on government funded research agencies, many excellent research programs have been shuttered. However, at SHRO, we have built a research program using innovative sources of funding to continue our mission to find a cure for this deadly disease. We have also built a collaborative network of international researchers at SHRO. Collaboration is key to the future success in cancer research.
4. Many cancers can be preventable. We have shown links between environmental contamination and the incidence of cancer around the Campania region in Italy. In addition, it is clear that asbestos remediation and the bans on use of asbestos have reduced mesothelioma incidence. We have also shown that a Mediterranean diet confers epigenetic changes that can reduce the incidence of many cancers and that lifestyle changes are important in reducing your risk to develop cancer. The link between smoking cessation and decrease in lung cancer rate is very strong.
5. Cancer is also a disease of misregulation. Many years ago I showed how misregulation of the cell cycle resulted in uncontrolled proliferation, which was the first direct evidence that cell proliferation is a hallmark of cancer. We have also shown that multiple genetic and epigenetic changes occur in the cell to cause cancer. In addition, our work has shown how misregulation of many cellular signals can induce altered proliferation and induction of cancer. Now we are designing gene therapies and small molecules to revert the changes in hopes of halting the growth of cancer. For instance we are looking at gene therapies to reactivate various tumor suppressors which would reduce the proliferation of cancer cells.
You are a person of great influence. If you could start a movement that would bring the most amount of good to the most amount of people, what would that be? You never know what your idea can trigger. :-)
Actually, the work we do at Sbarro Institute is one of my proudest achievements, the ability to mentor the young scientists of our time. This is very important for the future of medicine and research.
How can our readers further follow your work online?
The best way to follow my work at Temple University as well as the work of the Sbarro Health Research Organization is the following websites:
or contact me at antonio.giordano@temple.edu or president@shro.org
or at my Twitter @profgiordanoa
Thank you so much for these insights! This was very inspirational and we wish you continued success in your great work.
