AsianScientist (Jul. 12, 2023)–“I don’t see my objectives in analysis as being essentially completely different from my objectives as a doctor. For each, it was a want to assist sufferers with life-threatening illnesses,” shared Dr Ong Sin Tiong, Affiliate Professor at Duke-NUS Medical School, Singapore.
Dr Ong accomplished his housemanship coaching at Addenbrooke’s Hospital in Cambridge, United Kingdom, after which he returned house to finish his medical residency on the Nationwide College Hospital Singapore. He then left for the US the place he joined the fellowship program in hematology/oncology on the College of Chicago and later grew to become an attending doctor on the College of California. Round this time, he started to work on continual myeloid leukemia (CML), particularly to know the mechanisms of drug resistance.
Since then, Dr Ong has constructed a profession in fundamental and translational analysis, which, during the last twenty years, has resulted in three scientific trials arising from discoveries made on the bench. Whereas he nonetheless sees sufferers, he’s now extra more likely to be present in a lab.
“I focus extra time on analysis as a result of I see it as a manner of bettering the care of many sufferers around the globe, as an alternative of simply the one affected person sitting in my session room,” he defined.
Dr Ong has gained recognition for his seminal analysis on hematologic cancers, particularly CML. By 2040, CML is projected to be essentially the most prevalent leukemia in the US with 180,000 cases. Areas with a low socio-demographic index—a measure of socio-economic growth—like Southeast Asia have additionally been reported to expertise the highest CML burden.
Many sufferers with CML stay on pricey focused remedy for all times and need to cope with important points associated to drug side-effects and impaired high quality of life. Furthermore, for sufferers who reply poorly to focused remedy, their CML might rework into an aggressive type of the illness termed blast disaster (BC). At that time, the survival fee is low until a bone marrow transplant is obtained.
CML stimulated Dr Ong’s curiosity as a result of though the drug was hitting the goal, there was a scarcity of an entire understanding as to why some sufferers exhibited resistance to focused remedy.
In 2012, he and his group found an East Asian-specific polymorphism within the BIM gene which influences a affected person’s resistance to focused remedy. They discovered that sufferers who inherited a model of the gene—which they termed the BIM deletion variant—had inferior responses to focused remedy for CML. Importantly, as a result of they uncovered the mechanisms by which the variant brought about resistance, they had been capable of predict that the variant would additionally trigger resistance in lung most cancers sufferers present process focused remedy to the epidermal progress issue receptor (EGFR).
“Mechanisms-based analysis permits us to increase the findings made in CML, a mannequin malignancy for most cancers focused remedy, to different cancers. It’s also an instance of how being a scientist will increase the attain of your discoveries to sufferers past your clinic,” he elaborated.
This CML analysis is among the many breakthroughs Dr Ong has made with the Cancer and Stem Cell Biology (CSCB) group at Duke-NUS. He began the group in 2007 upon his return to Singapore. He felt assured that the novelty of the then two-year-old graduate medical faculty would foster an open setting conducive for impactful discoveries and translational analysis.
At Duke-NUS, Dr Ong and the CSCB group had been additionally instrumental within the development of ETC-206, a home-grown blood most cancers drug. In collaboration with the then Experimental Therapeutics Centre (ETC; now generally known as the Experimental Drug Growth Centre) of the nationwide Company for Science, Know-how and Analysis, they recognized the MAP kinase-interacting kinases (MNKs) as a drug goal in BC CML. ETC-206 began scientific trials in late 2016 and has since been licensed to a biotechnology firm.
From this analysis, the group has began investigating the position of MNKs as a drug goal in different cancers, resembling glioblastoma and breast most cancers. For Dr Ong, as a clinician and as a bench researcher, the entire expertise is very instructional, rewarding and helpful. He continues to increase the understanding of focused remedy resistance in CML alongside the group. Of their newest publication, they problem the long-held assumption that resistance solely emerges after the drug remedy is run.
“The dogma within the subject is that resistance to focused therapies is acquired solely after remedy begins and arises from most cancers cells that develop mutations which confer drug resistance. In CML, what we’ve found is that for main drug resistance, the die is solid even earlier than you begin therapy. The group, in collaboration with Dr Shyam Prabhakar on the Genome Institute of Singapore and Dr Charles Chuah on the Singapore Normal Hospital, uncovered eight components that decide how nicely a specific affected person goes to do,” Dr Ong stated “These findings will permit us to determine sufferers destined to develop drug resistance and BC CML after they first current in addition to start forming therapeutic approaches to nip drug resistance within the bud.”
![The CSCB team with Dr Ong](https://www.asianscientist.com/wp-content/uploads/2023/07/1024x607-Team-image.jpg)
The mission of the CSCB program at Duke-NUS is to advance most cancers analysis and make discoveries which can be related to Singapore and past. This system has since co-developed two most cancers medicine with ETC, specifically ETC-206 and ETC-159 (which is focused at a spread of cancers).
“I imagine we’re fulfilling the mission of our faculty in reworking medication and bettering lives. Collaboration is vital to having the ability to do that. In case you have a look at our papers, you’ll see that we’ve solely been capable of obtain our objectives by harnessing the experience and energy of many native and worldwide colleagues. We hope to proceed serving as a catalyst for these collaborations,” Dr Ong stated.
The CSCB program additionally performs a task in educating the subsequent era of clinicians, researchers and clinician-scientists. Dr Ong encourages college students to pursue their scientific goals however cautions that as a result of the journey forward is lengthy and difficult, creating a private roadmap that’s each significant and pleasant is essential.
He suggested, “Earlier than you embark on this journey, it’s good to attempt to perceive what you need out of your profession and life. For me, working as a clinician-scientist is the place significant work and enjoyable intersect. Some have described science as being a severe type of play, so having the ability to ‘play’ and, on the similar time, make discoveries that may assist most cancers sufferers is the right calling for me.”
In his personal journey, Dr Ong pursued a medical diploma as a result of he was fascinated with serving to folks in want by leveraging his curiosity in science and making his personal discoveries. His curiosity and optimism about the way forward for most cancers analysis and a want to enhance the administration of life-threatening illnesses have sustained his unwavering ardour up to now.
Reflecting on his profession in Singapore, Dr Ong is heartened to look at the sturdy footing that native scientists have established in world most cancers analysis. Beforehand, a lot of the analyses achieved on native samples relied on researchers exterior the nation. Now, researchers flip to Singapore for experience.
“This modification is a testomony to the ability of collaboration and the worldwide recognition that most cancers researchers in Singapore have achieved. That’s one thing for us to be very happy with, however it’s also one thing that we should preserve working actually exhausting at to take care of. We’re solely pretty much as good as our final paper,” he stated.
With most cancers nonetheless the highest reason behind loss of life in Singapore, Dr Ong says there’s extra work to be achieved. The arrival of more and more superior technological instruments will allow extra insights into understanding the mysteries of most cancers. The problem then lies in how researchers can leverage the instruments to translate these discoveries into simpler affected person care.
For extra data on the analysis carried out by Dr Ong Sin Tiong and the group by the Most cancers and Stem Cell Biology program, go to this system’s web site here.
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Supply: Duke-NUS Medical College
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