MAY-JUNE , 2022 | THE HEALTH

BY KHIRTINI K KUMARAN

Dr Tan is the Founder and Executive Director of the Gillies McIndoe Research Institute ( GMRI ); and Consultant Plastic Surgeon at Hutt Hospital , Wellington , New Zealand .

Born to a poor family of 14 children in Senggarang , Batu Pahat , Johor , he aspired to become a doctor . He enrolled in the medical school at Melbourne University , Australia , in 1980 and later trained as a plastic surgeon in New Zealand .

As a plastic surgeon , Dr Tan managed patients with disfiguring and lifethreatening conditions and finds many existing treatments are unsatisfactory , invasive , and costly .

“ I believe we need to go to the lab and try to better understand these conditions , which will allow us to design an effective , inexpensive and convenient treatment for patients .

So in 1996 , he enrolled in a part-time PhD programme at the University of Otago to better understand strawberry birthmarks and develop a better way to treat the problem .

Improving strawberry birthmark treatment

A strawberry birthmark consists of a clump of tiny blood vessels that form under the skin . It causes a raised red skin growth that is usually present within 2-3 weeks after birth . It is a benign ( non-cancerous ) tumour .

They usually grow rapidly for a few months , stabilise in size , and then gradually subside over a few years , often leaving a fatty lump or skin blemish . However , the location and size of the growth may affect bodily functions such as impairing eyesight or blocking airways . It also significantly affects one ’ s appearance and self-esteem .

For such cases , traditional treatments involved initial high-dose steroids and sometimes chemotherapy , often followed by surgery and / or laser therapy , which Dr Tan believes are too harsh on the children .

“ After 15 years of work , we found that strawberry birthmark is caused by stem cells with evidence that they originate from the placenta . We discovered the involvement of the renin-angiotensin system ( RAS ), a regulatory system known to control blood pressure .

“ These discoveries underscore the way we treat strawberry birthmarks now , using blood pressure-lowering drugs that make strawberry birthmarks shrink and disappear .

“ The RAS consists of many steps , and we have existing medications that can be used to block each of the steps . For example , we can use beta-blockers to block the system to treat strawberry birthmarks .

“ Propranolol , a beta-blocker , is now the treatment of choice for strawberry birthmark since 2009 . It is a simple and costeffective treatment , taken orally , and the patient is not required to be in the hospital . As the RAS can be blocked with other medications such as angiotensin-converting enzyme ( ACE ) inhibitors , Dr Tan and his team conducted a clinical trial using the ACE inhibitor Captopril to treat strawberry birthmarks , at Hutt Hospital .

“ This was the world ’ s first-ever clinical trial using this approach to treat a tumour .”

Drug repurposing for cancer treatment

Based on the research breakthrough with strawberry birthmarks , Dr Tan and his team researched cancer stem cells , the proposed origin of cancer , and found that the RAS is expressed by cancer stem cells in 14 cancer types , including brain , skin , colon , and lung cancers .

“ Cancer stem cells are highly tumorigenic and possess self-renewal properties , which is why cancer can recur and spread , forming new tumours , and resists conventional treatment ,” he explained .

“ So , this potentially allows us to intervene and control the cancer stem cells by blocking various steps of the RAS by repurposing well-established drugs .”

Glioblastoma , the most common and most aggressive form of brain tumour , was one of the first cancers Dr Tan and his team investigated . They have now designed a phase II clinical trial for glioblastoma patients .

Drug repurposing , said Dr Tan , is hugely less expensive than developing a novel drug and takes less time to reach the market . He , however , noted as there are no commercial incentives , the GMRI relies on philanthropy to support their drug repurposing research .

Dr Tan ’ s team has received regulatory approvals to proceed with the phase II glioblastoma clinical trial and they are actively seeking philanthropic donations it get off the ground .

GMRI ’ s research focus

While working on his PhD , Dr Tan decided to establish a research institute , and the GMRI was officially opened at the end of 2013 by former New Zealand Prime Minister Sir John Key .

The GMRI ’ s research focuses on the role of stem cells in diseases such as cancer ,

Dr Swee Tan

A baby with strawberry birthmark affecting her cheek and eye treated with Propranolol .

PET scans of a patient with glioblastoma before ( left ) and 3 months following initiation of the GMRI trial medications ( right ) showing reduced tumour volume and activity .

The official opening of the GMRI by the former New Zealand Prime Minister Sir John Key .

fibrotic conditions , vascular birthmarks , and regenerative medicine .

“ We are also working on organoid systems by creating a microscopic organs in the lab that allows you to investigate certain conditions and test drugs with different concentrations and combinations . So , we are developing organoid systems for glioblastoma , colon cancer and lung cancer .

“ It ’ s an exciting area of work that we ’ re doing . It will give us a platform to investigate these conditions . And of course , the knowledge can be applied to developing other organoids .”

As for the future of managing haemangiomas , he believes in continued research and hopes to improve and refine treatment for strawberry birthmarks and the other types of vascular birthmarks .

The GMRI is a non-profit organisation supported almost exclusively by philanthropic donations . Dr Tan shared the pandemic had affected their funding because governments and people worldwide were focused on Covid-19 .

“ Reduced funding and lockdowns have undermined our ability to make progress on time . Everything was hard .”

Despite the challenges , Dr Tan is pleased to continue his work and humbled by the contributions and participation of those eager to help humankind . — The Health