Advancing Cancer Research: A*STAR Scholar Discovers Genetic Vulnerability in Breast Cancer Cells

A*STAR scholar Peter Yeow has made a landmark discovery in breast cancer research during his PhD study.

“I actually started out on a completely different project, where the hypothesis I was testing proved to be incorrect,” says Peter Yeow, an A*STAR scholar at the University of Oxford. “Serendipitously, this led to two key pieces of data that I was able to piece together to form the central hypothesis of the published study.”

Riveted with the fact that cancers arise due to changes in genomes, Peter always yearned to harness the current wealth of knowledge on genetics to develop novel therapeutics for cancer. This was what led him to focus his PhD research on cancer genetics, to explore how certain cancers such as breast cancer could be selectively targeted for treatment.

In September 2020, Peter was part of a team of researchers from his university to announce a groundbreaking discovery of a genetic vulnerability that is present in 10% of breast cancer tumours. The team has also identified a way to exploit this in therapy to selectively kill cancer cells while leaving the surrounding healthy cells unharmed.

Peter was the lead author of the study that was published in Nature journal.

Peter analysing the results of an experiment with a colleague at the Wellcome Centre for Human Genetics, in Oxford.

Identifying and targeting genetic vulnerability in breast cancer

Around 10% of breast cancer tumours possess a unique characteristic – an abnormal repeated region on chromosome 17. Called the 17q23-amplified cancer, Peter and his team discovered that these breast cancer cells cannot survive without centrosome, which is a cellular structure that supports normal cell divisions. Working with researchers from Johns Hopkins University, the team then revealed that these breast cancer cells have faulty centrosomes, which leads to mistakes during cell division.

“Daughter cells born of these abnormal cell divisions are more likely to acquire new genetic mutations. This is known as genomic instability, one of the hallmarks of cancer which makes 17q23-amplified cancers aggressive,” explains Peter.

Fortuitously, the team revealed that this trait that makes the cells more malignant also makes them more susceptible to losing their centrosomes. They demonstrated that this weakness could be exploited by introducing a chemical which causes the cancer cells to lose their centrosomes and die.

“These findings hold potential for therapeutics to be developed not just for breast cancer patients, but also patients of other cancers with the 17q23 amplifications,” he adds.

Honing skills at A*STAR to contribute to global research efforts

Peter attributes much of his achievements to his mentors from A*STAR: Prof Sir David Lane, A*STAR’s Chief Scientist and Director of the p53 Laboratory, and Dr Walter Goh whom he grew acquainted with during his attachment at A*STAR as an undergraduate student. “It was at the p53 Lab where I first cut my teeth as a student researcher. I was exposed to top quality science and world leading researchers on a daily basis. I was fortunate to be able to pick up essential lab techniques that helped ensure a smooth transition into my PhD study.”

After graduation, he was awarded the A*STAR National Science Scholarship (PhD) to study Clinical Medicine at the University of Oxford. “I am utterly grateful for the scholarship, which afforded me the resources to fervently pursue my PhD at Oxford without being held back by any financial worry. The scholarship had enabled me to embark on an ambitious and long-term project.”

Peter (middle) with schoolmates at the University of Oxford.

All work and no play makes Peter a dull boy

Peter admits that the four years of grad school was intense, and sometimes filled with pressure from the various challenges that arose, such as needing to coordinate research between universities and facing a steep learning curve to produce publication-quality data. However, he had learned to tune out from the stresses by playing or watching football, which he passionately pursues in and out of school. “I’ve also learned to enjoy slow walks in the evening with friends, as walking allows me to have conversations while going at a pace where I can appreciate my surroundings,” he says.

Peter (middle) in a game of football at the annual Oxbridge Games in school.

Other than sports, Peter is passionate about coffee and food. At home, the research student enjoys experimenting with different brewing methods and beans. “This could be a hit or miss, but nothing beats a perfectly brewed cup of filtered coffee in the morning to start my day,” he quips.

When asked about his future plans, Peter said that he looks forward to continue in the same area of research and to align his expertise and aspirations into the wider research ecosystem in Singapore.

“Our findings constitute the first step of the drug discovery pipeline, and there is still much follow-up work to pursue. For example, anticipating how cancers could become resistant to this form of treatment will allow us to stay one step ahead.”

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