By President Kim Hyung-dae, Reporter Paul Kim
"Research collaboration with National Cancer Center (NCC), which has excellent analytical skills and resources for proteogenomics, will enable the identification of more reliable biomarkers for a variety of carcinomas and ultimately take a major step forward in cancer conquest," said Director Henry Rodriguez of the Office of Cancer Clinical Proteomics Research at the National Cancer Institute's (NCI) of the United States. Director Rodriguez made the remarks at the 13th NCC International Symposium held at NCC Hospital in Ilsan on June 28, 2019.
The symposium was attended by distinguished experts from various countries engaged in preventing, diagnosing and treating cancer including Director Henry Rodriguez of the NCI, President Lee Eun Sook of the NCC and Dean Park Jong bae of Graduate School of Cancer Science and Policy, also known as the Head of the Cancer Proteogenomics Working Group of the NCC.
During the event, a Memorandum of Understanding (MOU) on Clinical Proteogenomics Cancer Research was signed between NCC and NCI with the purpose to strengthen mutual cooperation on proteogenomics cancer research.
Director Rodriguez stressed that he hopes that something positive will come out of the partnership that does not just benefit the Korean population but all cancer patients.
Established in 2000, NCC’s effort for international cooperation began in 2015 signing MOU with The University of Texas M.D. Anderson Cancer Center. Now, it has become one of the world’s leading institutions in reducing the burden of cancer by developing strategies suitable for rapidly changing times.
Proton therapy is one of the accomplishments that made NCC a leading cancer institute.
Unlike X-ray therapy, which is generally used in many institutions, Proton therapy is a type of radiotherapy that cures cancer without damaging neighboring healthy organs and cells. NCC is among the only two institutions in Korea that provide such treatment.
The leadership of President Lee Eun Sook of the NCC is another accelerator of making NCC bright.
As the first woman ever to become the President of the NCC, she graduated from Korea University in Seoul with honors and obtained her Master’s degree in Medicine and Ph.D. for Medical Science. More than 8000 breast cancer patients had gone through her hands not only treating cancer but to rejuvenate their lives as women. Her recent goal is to develop a technology with an AI program in rooting out the cause of 99 different types of cancer. Through this technology, she intends to not only help the patients in South Korea, but also the North.
With cancer as a leading cause of death around the world, it is responsible for one out of every three deaths in Korea. The cause is projected to increase in the coming years. However, according to WHO, one-third of all cancers can be averted through preventive measures such as anti-smoking, vaccinations, and a healthy diet & lifestyle. Another third can be cured by early detection, and the remainder can be overcome through medical research. In this sense, establishing a platform to share enough information to prevent and resolve war against cancer has become an essential task for all.
For more understanding of recent research on cancer, an interview was conducted with Director Henry Rodriguez of the NCI, as follows:
Question: What is proteogenomics?
Answer: The field that we currently consider next-generation molecular medicine, including genomics, proteomics, miRNAomics, microbiomics, and epigenomics, all share the same foundation. That foundation rests on "-omics," which is an informal term used to describe the comprehensive study of the biological component of a cell at the molecular level.
Take genomics as an example. Genomics is the comprehensive study of the complete set of genes or DNA in an organism, which we refer to as the genome.
Analyzing the genome of a patient's cancer can reveal information about how to best detect, diagnose, and treat the patient.
A patient's cancer may have a DNA mutation that makes it especially sensitive to a drug. Although studying a patient's DNA can provide much information, it doesn't give us the whole picture. The reason is that, in addition to DNA, many other molecules contribute to cancer biology.
ince then, we have found out that we can only get a partial picture when researching genomics and proteomics separately but studying them together produced a more complete unified picture. In the past, researchers often studied the two entirely separately. However, in 2016, researchers combined the comprehensive analysis of patients’ cancer genome and proteome and made a new approach called proteogenomics. This is where proteomics comes in. Proteomics is the comprehensive study of the complete set of proteins in an organism which we refer to as the proteome. Proteins are built from DNA and play a significant role in the daily functions of both healthy and cancer cells. Analyzing a patient's proteome can also provide information about how to best treat diagnose and treat the patient.
We are hopeful that proteogenomics will improve our ability to prevent, diagnose, and treat cancer at the molecular level.
A: So, the perks for me is being able to unravel and understand a disease that hasn't been explained before. It's the same perk you get when new technology comes around. I view the idea of combining the two omics – proteomics and genomics – as par with my philosophy when I talk about science and technology.Q: What are the perks and drawbacks of studying proteogenomics?
Technology today enables me to not just ask in biology but also address them by producing information content. If we think about it, every time we provide data, we expect to extrapolate knowledge as humans are curious individuals by nature. Such curiosity enables us to ask further questions, and for such instances, the current technologies don't satisfy the answer we are looking for, and it forces us to develop new technology.
I see the idea of blending genomics, a field that has been matured, with proteomics, which is an emerging field, as a philosophy and capitalizing on the idea.
The cons of proteogenomics happen to be the complexity of the research. This is because the more things we add to analyze, the more complex it is to understand the correlation between the two.
However, to be quite candid, the challenge is okay as I rather have more information that enables us to move a little bit toward a solution than not having that information at all.
Q: How can proteogenomics help achieve precision medicine in the clinical oncology field, which had been historically dominated by genomics research alone?
A: The first draft of the genome project started in 2002. What happened at that point was tremendous enthusiasm on what we could do with genomics, but at the same time, researchers began to ask is genomics the only aspect that can help us achieve precision medicine.
At that point, what happened was that researchers turned toward proteogenomics to look for a better and accurate solution. However, very early on, controversial papers and finding focused on biomarkers gave false hope to researchers.
The NCI at that time recognized the value and trusted the information coming out of the genomics-based approach. When it came to proteins, however, the institute realized that it added value, but questioned if we could apply this new methodology which came with another study that could have faulty results in the data.
So the institute took a very conservative approach.
In my view, I agree there was a massive drive in oncology using genomics, but it had a window of years before the protein phase to be able to produce all that data.
Also, to its credit, it has a higher throughput space and costs lower than obtaining protein information.
However, such benefits do not mean that proteogenomics is useless because at the end of the day what we as researchers are trying to do is understand the biology and complexity of the disease first.
Once we get to understand the disease, then we can decide which one of these omics best correlates with the disease itself and adds value to the patient care.
Q: What are the pros and cons of making it an international activity?
A: This scientific terminology comes out from a scientist called Jake Jaffue who has coined this terminology years before. The only distinction that in the US of which I happen to lead refers to a CIPITAC and its one of these programs at NCI called the extra mirror program. This means that I serve as more on a problematic level and the recipients and all the artisans which produce all these beautiful sciences, it is the academic community. And what we ended up doing at the Cancer Institute is taking a gamble, which is what I love when you gamble. And the gamble for us was a simple one early on, which was once we understood the analytics of this protein world, we had something called the strategic workshop. We bring in outside experts and you basically ask them. So now we have the data, and what do we do with this now? With these analytical workflows that we believe to regenerate the representative of biology not just some artifact of the way, you do things upstream producing the data. The recommendation that literally came back as they said, “You know the program that you do at the NCI, we want you to grab those samples and you are going to layer this biology right on top. And in the end, the hypothesis is simple. Can you or can you not find something that they could not find? Because the real underline message is, if all you do is confirm, what genomics base does, DNA and RNA, or if you don’t find anything new, help me understand what you bring to the table.” That literally was the hypothesis. Fortunately, the gamble paid off. We were always able to find additional biology behind it. Whether it has a clinical indication I think that just signs progress time will tell because I think that needs to move forward. Taking it on a global scale, the challenge simply happens to be how do you coordinate the activities of different countries.
Q: Can researching proteogenomics solve the treatment-resistance issue in cancer therapies?
A: It is currently unclear as it still needs time to show a real outcome in the clinical field. However, that is the goal we are hoping to achieve.
We know today that patients can either develop toxicity or resistance toward treatment, but we don't know the exact cause.
The hope and promise we hope to get out of proteogenomics are to unravel the biology in developing such resistance and toxicity and give us predictive markers that can help us determine how an individual is going to respond to treatment.
However, I can't say for sure when we are going to have such results as biology takes time and is a very complicated area.
Q. What are the pros and cons of making this initiative into an international activity?
A: So, to be very fair, this science and the idea of using this terminology actually came out years before. The only distinction that I think of which the program I happen to lead refer to a CIPITAC and its one of those that the NCI calls as an extra mirror program, which means that I serve in a more problematic level and all those recipients, or to say the artists who produce this beautiful science, it is the academic community. And what we at the cancer institute ended up doing is that they took a gamble, which is what I love when you gamble. The gamble for us was what we saw early on – proteogenomics. Once we understood the analytics of the protein world, we had something called the strategic workshop.
Q: When will proteogenomics make an impact on patients' lives?
A: We're hoping to get a session this coming year at the American Association for Cancer Research (AACR) and present our research. However, implementing our research into patients' lives is still way down the road.
The NCI is currently partnering with various clinical trials. The objective is not to take the information back to a tumor board, but to find out what makes the individuals respond or don't respond to treatment.
By layering the biology on the clinical trial, the institute hopes to reverse engineer and show why the treatment worked or did not work.
If we can show results, then we can say that our research could add value and start opening doors to developing a treatment.