With recent advancements in sequencing technologies, scientists are no longer required to rely exclusively on proteomic or genomic information. To this end, proteogenomics, which combines the two areas, has recently become one of the most actively studied areas in the world to analyze and identify targets that cause cancer for accomplishing precision medicine.
To achieve such goals, proteogenomics gives a systems perspective, viewing the genome sequence, RNA expression, protein synthesis, and post-translational modifications all at once.
Although proteogenomics expands quickly as part of the systems biology trend, which is the computational and mathematical analysis and modeling of complex biological systems, it is still at an early stage and is not well known in Korea.
Korea Biomedical Review met with Henry Rodriguez, director of U.S. National Cancer Institute's (NCI) Office of Cancer Clinical Proteomics Research, at "13th National Cancer Center International Symposium," to better understand what proteinogenomics is and what it holds in the future for patients and precision medicine in the field of oncology.
|Dr. Henry Rodriguez, NCI’s director of Cancer Clinical Proteomics Research, explains the importance of proteogenomics in the field of precision medicine, in an interview with Korea Biomedical Review. The meeting was made on the sidelines of the 13th National Cancer Center International Symposium at the National Cancer Center in Goyang, Gyeonggi Province, on Friday.|
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.
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.
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.
Since 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.
We are hopeful that proteogenomics will improve our ability to prevent, diagnose, and treat cancer at the molecular level.
Q: What are the perks and drawbacks studying proteogenomics?
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.
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 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 those 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: 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: 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.
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