The recent research result from the Department of Bio and Brain Engineering for identifying the optimal drug combinations to enhance p53-mediated apoptosis of MCF7 breast cancer cells created a stir in the science academia and raised hopeful questions from the general public. The KAIST Herald went to interview Professor Kwang-Hyun Cho’s research team, Professor Cho and Minsoo Choi in particular, to hear the behind story.

Please give a brief explanation about the research.
[Choi] Signaling pathways are complex regulatory interactions that have to be dealt as a network of systems to attain information on how individual components affect each other. We used a computational approach called attractor landscape analysis to see how the state activities of p53 and its surrounding regulatory molecules fall into the different attractors created by the change in landscape. Different attractor landscapes triggered different cellular responses to DNA damage. Using this analogy as well as the Boolean modeling method, we analyzed how molecular nodes adjust themselves around p53 to lead to apoptosis. Also, graphing the computational prediction in three dimensions, we found that nutlin-3 and Wip-1 inhibitor combination have the ability to enhance the apoptosis response to DNA damage.

How do you feel about the result as of now? How do you plan to take it further?
[Professor Cho] This particular research took about five years. We are very glad that our research got some valuable results. Our thesis was selected as the Editor’s Choice in the weekly magazine Science and was introduced as the cover thesis in Signaling Science. We are also very grateful that KAIST is helping us prepare and apply for Private Communication Protocol (PCT). As for our future plan, we are looking forward to verifying the result with in vivo experiments and clinical trials on patients. We are also hoping to try out more drug combinations for not only breast cancer but also cancer of other kinds and possibly heart diseases.

What are the benefits of applying systems biology to biological research?
[Professor Cho] Systems biology involves the overlapping of various different fields of studies that range from biological sciences to mathematics. Rather than using the conventional heuristic approach to discovery, systems biology aims to find optimal solutions at the overlapping borders between different studies. Going beyond simply defining functions by analyzing mechanisms, we seek to find solutions to control problems by understanding the fundamental biological principles. Studying the interactions between the smallest units of entities helps us understand the overall system of network.

As the only systems biology lab in Korea, what is your outlook on Korea’s scientific research?
[Professor Cho] Korea does not have the capital strength to support extensive scientific research in all areas. So far, only the researches with a chance of success have been getting continuous support. When it comes to systems biology, there has not been much interest in it, and consequently not much support for this kind of research. In order to compete worldwide, with the large capital strength, however, we need to seek a shortcut for the development of new pharmaceuticals. I believe systems biology could be the key to solving the financial problem. We have many talented IT students and professionals to help us venture further and bring down the boundaries between different areas of research. I believe this will allow us to do more effective systems research and further development of pharmaceuticals. It could be a start to bring about a paradigm shift.

What would you like to say to patients who are waiting for better drugs without side effects?
[Professor Cho] As for cancer, it is something we have to take as our destined fate. We already have so many systematic safety devices within our biological systems that the occurrence of cancer is considered an unusual case that we have to deal with. Patients need to learn how to cope with cancer effectively and live to fight against it. Our goal is to develop patient-tailored cancer chemotherapy via systems biological tactics. As for our research, we are expecting a lower chance of side effects when it comes to developing it into drugs because even in normal cells, miR16 inhibits Wip-1 to cause apoptosis in response to DNA damage. Unfortunately in cancer cells, nutlin-3 or Wip-1 inhibitor alone does not have such a powerful impact, but when combined together, they produce a synergy effect, leading to apoptosis. Since miR16 induces Wip-1 inhibition in normal, noncancerous cells, we are expecting that the drugs developed based on our results will not have such extreme side effects.

What would you like to say to KAIST students?
[Professor Cho] I want students to look beyond what they are studying at the moment. There are many areas of interesting subjects other than your major. There are many possibilities that can come about when you reach out to different fields. I believe this is where imaginative thinking emerges.
[Choi] I think it is important to have passion and patience when it comes to doing research. The outcome of research is not about talent, but the amount of effort and time you put into it. Also, do not be afraid to face challenges. Oftentimes, this is where you discover your passion.