Researcher targets precision strike at cancer cells

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Oon observing image of blood vessels on tissue sections.

Associate Professor Dr Oon Chern Ein of Universiti Sains Malaysia (USM) has received many accolades for being a game changer in her scientific pursuit which is largely focused in discovering new potential targeted therapies to treat cancer. She shares her thoughts on her work and the need for communicating science to the public with SHAMIRA SHAMSUDDIN

Tell us about your background.

I had many interests and ambitions from aspiring to be an educator, a doctor to becoming a fashion designer. What sparked my interest in science is the fact that my father specialises in chemistry and he used to explain things from a scientific point of view for everything that happens around us. However I love biology, especially the human anatomy. Mom told me that if I chose to be a fashion designer, I would have no future in Malaysia unless I made it really big. Being a medical doctor would mean getting married to the hospital and I would not have time to nurture my family. So, I chose research.

My PhD research at University of Oxford has challenged the initial belief on formation of blood vessels in cancers that positively correlate density to tumour growth. Together with others, we discovered that the importance of blood vessel function based on size and perfusion far outweighs that of vessel density in contribution to tumour progression.
During my postdoctoral training at Karolinska Institute in Sweden, I worked on identification of new cancer proteins expressed within the tumour microenvironment (cells surrounding the cancer) and tried to understand how Sirtuins, which are enzymes that are up-regulated in certain cancers may render cancer to be less responsive to chemotherapy.

Tell us about your research and what inspired you to venture into it?

Currently, my work focuses on the effect of novel cancer therapeutics on genes and proteins in cancer to bring findings from bench to clinics. Of particular interest is a new compound that blocks the Sirtuin enzymes in cancer. With three patents pending, the compound has been demonstrated to effectively kill cancer cells with no toxic effect in healthy tissues.

Molecular targeted therapies are revolutionised therapeutics which interferes with specific molecules to block cancer growth and progression. Our compound can inhibit the sirtuin enzymes on colon cancer cells expressing these molecules, while exhibiting minimal toxicity effect on normal cells in cell based assays and in mice. The compound also modulates different cancer pathways in colon cancer with different mutation profiles, suggesting that it could be used as an adjunct in combination with other pathway inhibitors to improve therapeutic outcomes (Published in Future Medicinal Chemistry, 2018).

I am a people person. I believe in finding relevance for the work that I do, and the people should benefit from the work that I do. When I received the offer to pursue my PhD at University of Oxford, I spent two months volunteering at pathology and cancer units in local hospitals to be able to understand the circumstances that daunt cancer patients. Ten years down the road, I fulfilled that dream in becoming a cancer researcher trying to find new treatments for cancer.

 

 

 

 

 

 

What are some remarkable achievements by far?

We have now entered pre-clinical studies to investigate the toxicity of this compound and the metabolic processes in mice model. Ideally, we would want a drug that shows no toxicity and does not induce chromosomal damage.

So far, results have been promising. We are currently employing artificial intelligence to predict drug combination efficacy of our compound in colorectal cancer through international collaborations. Some other on-going studies include using computer modeling to predict drug targets in cancer. As with drug discovery and development, this drug candidate still needs many more years of research to see its efficacy in clinical trials.

As for the accolades received pertaining to this area of my work includes the Ranjeet Bhagwan Singh Medical Research Trust Fund 2014 (sole recipient-awarded by Academy of Sciences Malaysia and Ministry of Science and Technology), EXIQON Young Scientist Award- South East Asia 2014 (awarded by EXIQON), L’Oreal-UNESCO for Women in Science National Fellowship 2015, and the MAKNA Cancer Research Award 2016 (awarded by National Cancer Council Malaysia).

This work has also received funding from two prestigious international bodies to establish collaborations abroad including the International Transfer of Cancer Research Knowledge and Clinical Technology Fellowship 2016 (awarded by Union for International Cancer Control, Switzerland) and the Royal Society Flexi Grant 2018 (UK). In 2018, I was awarded the Women of The Future Award- South East Asia (UK) and the National Young Scientist Award (Ministry of Science and Technology Malaysia) for being a game changer in the field of cancer therapeutics in Malaysia.

I believe that these awards are not merely for me to boast about but I should use these as platforms to drive positive changes and be a voice that can be heard. Winning Loreal-UNESCO for Women in Science taught me the importance of communicating scientific research to the public. It was the first time my research was put in the spotlight and I had to learn to relay my research to lay people. Being the first Malaysian to win the Women of

The Future Award (WOF) South East Asia (UK) has strengthened my drive to empower women and strive for fairness and equality especially in pursuing a career in science.

How would you explain your work to the public?

Traditional chemotherapy functions by killing rapidly dividing cells, regardless of whether they are cancerous or not. Targeted therapy is different. It works by stopping the communication of a particular cancer protein, thus, deactivating it to hinder the growth and spread of cancer. Only cancer cells or the surrounding cells that support cancer growth which express the targeted protein (Sirtuins in my case), will be specifically killed by the targeted drug, leaving healthy tissues that do not express these proteins unharmed.

How would your research benefit cancer patients?

Our key findings accentuate the importance of customising treatments to patients with different cancer mutation profile to ensure optimum treatment outcome, which holds the basis of precision medicine. Precision medicine allows the doctor to give the right treatment at the right time to the right patient to improve therapeutic outcome. If successful, this compound holds the potential to be developed as a drug candidate for treatment of cancer (not limited to colorectal cancer but also other cancer types with KRAS mutation which is a type of mutation found commonly in colorectal cancer that cause majority of patients not to respond to many treatments including anti-epidermal growth factor therapy).

What inspires you to engage in science communication despite your full time academia and research obligations?

I work on molecular targeted therapy, an area that is very much established in the west and Singapore, but in Malaysia this area was not well understood when I embarked on it in 2013. Molecular targeted therapy refers to the use of a drug candidate to block specific proteins highly expressed in cancer cells or cells surrounding the tumour but not abundantly found on healthy tissues to effectively impede tumour growth without causing too much toxicity as compared to chemotherapy. Malaysia is a nation blessed with the rich heritage of flora and fauna.

Hence our research and funding are very much focused on traditional medicine and nutraceuticals. People question the use of synthetic compound versus natural products with the mindset that everything natural should be safe. In Malaysia I received many unfavourable comments from professors reviewing my grants where rebuttals not welcomed.

As a young researcher trying to work on what I believe in, it was very difficult especially in a setting where seniority and positions speak louder than anything else, something which I was not used to.

Since I obtained my PhD and tried fitting in here, I have been told a number of times to change the direction of my project because I did not fit in.

The only way for me to make subtle changes was to try to educate people on my research area. I started writing layman articles together with my students in the hope to help people understand the concept of molecular targeted therapy and its use in cancer. Many people are also not aware that the cells surrounding the cancer can affect tumour response to treatments. I tried lobbying for publishers who are willing to publish my articles.

I started as a nobody, only a junior researcher with a dream to change societal mindset. I have been rejected in citing my articles are not of interest compared to other fields out there. I continued writing and looking for platforms to share our articles. We have been lucky to have been able to work with MAKNA, Scientfiic Malaysian and Majalah Sains to publish our work.

What kind of public engagement do you do?

In addition to writing layman articles, I work with Corporate Social Responsibility for Shangri-La, Penang Education Council, Penang Science Cluster and Young Scientist Network Academy of Sciences Malaysia (Chair of Science Outreach 2017-2018) to organise science workshops for underprivileged children and students from high-needs schools with the hope to inspire them to choose a career in STEM particularly medical sciences.

Some of these students were from arts stream, many have been pushed to choose the science stream only because their grades made it, but in reality they showed no interest in science mainly because the subject is too dry with little exposure to practicals as the schools were not well funded, according to the teachers.

Oon speaking to underprivileged children and students from high-needs schools with the hope to inspire them to choose a career in STEM.

As for the students from care homes, some of them are without proper identification documents or birth certificates as they were born out of wedlock, hence they had no opportunity to pursue formal education in school.

I also worked with MAKNA National Cancer Council to educate cancer survivors on cancer diagnosis and treatments through joined workshops and support groups. I have a vision to use my position as a scientist and educator to improve the research culture and ethics as well as to increase science literacy in Malaysia.

Why do you see the need for scientists to communicate to the public?

Science communication to laymen is gradually accepted as a responsibility of scientists. Poor communication between scientists and the public may negatively affect the ability of the public in making informed decisions which may impinge on judgements and interpretation of common issues faced in day-to day life. Hence it is important to educate and inspire the public in the bid to bridge the gap as well as to instill passion in science among the general public.

This comes from my personal experience of having school teachers and close friends telling me that they believed what they read on the mass media, such as drinking plant concoctions and taking herbs solely to cure stage four cancer over a short period of time.

Many patients first diagnosed with cancer will ask for opinion on the use of traditional medicine in favour of western intervention, a risky decision because of limited understanding and traditional beliefs. This may then affect the decisions made while seeking science-based cancer treatments. Hence, the very strong need to communicate and translate research findings to the public.

Do you think our scientists are doing enough to bring science and research to the public domain? What are the challenges?

I think scientists can do more than just being confined to the lab and chasing after KPI (Key Performance Index). In an environment too focused on KPI where numbers matter, people have forgotten that numbers do not equate to impact. Sometimes, it is in the journey itself lives are touched and changed. We could do a lot more for the public if we simply make our research translatable and relevant to the society. What was deemed “right” half a century ago may not be so in this era. Similarly, the public needs to be educated on the latest scientific discoveries and its daily use. Many news are hosted on social media and mass media, but the accuracy is often up to the interpretation of the viewers. This is where we as scientists and educators come in to play the role of bridging the gap of literacy between scientists and lay people.

What is your advice to young people who aspire to build a career in cancer research?

People will always challenge new concepts and new ideas. Do not be afraid to dream and think big, you are bound to face hurdles but never settle for less. A scientist should stay strong in defending what she/he believes in. To do good science is not about pleasing people around you or pursuing only mainstream ideas. It may be a journey full of ups and downs and you will feel alone in this fight but keep your focus on your goals and your passion will bring you through. True enough, I am now a strong believer of success being built upon struggles and failures.

NOTE: Dr Oon Chern Ein serves as a lecturer at INFORMM, Universiti Sains Malaysia. She is a member of the Global Young Academy, a fellow of the Association of Union for International Cancer Control and an ambassador of European Association for Cancer Research.