Taking on the stubborn cells that cause cancer relapse

Cancer is one of the leading killers worldwide, and finding a definitive cure has become the holy grail. Through her research, Dr Heather Lee and her team are coming closer to it by minimising relapse of acute myeloid leukaemia (AML).

Heather’s work involves investigating the inner workings of cancer cells and finding new treatments for blood cancer. This involves studying the ‘epigenetic’ processes that control how genes are used.

Epigenetic processes refer to changes in gene expression that don’t involve alterations to the underlying DNA sequence. Instead, these processes affect how genes are turned on or off through mechanisms such as DNA methylation, histone modification and non-coding RNAs.

Epigenetics is common and occurs in all plants and animals. In fact, it’s essential for normal development, cellular differentiation, and adaptation to environmental changes, as Heather explains:

“All around us, epigenetic processes are working silently to maintain the incredible diversity of life. The ripening of fruit, the coat of tortoiseshell cats, the social structure of honeybee colonies, even the growth of our bodies from a single fertilised egg; all of these are controlled by epigenetic processes.”

However, our health can be negatively influenced by changes in epigenetic processes. Cancers, cardiovascular diseases, psychiatric conditions and many other common disorders are characterised by altered epigenetic regulation.

More broadly, epigenetics is relevant to social issues, including environmental impacts on health and transgenerational trauma.

A single-cell epigenetics pioneer

Heather was first introduced to epigenetics during her PhD at the Garvan Institute of Medical Research in Sydney, where she investigated hormonal control of mammary gland development and breast cancer.

It was as a result of her work at Garvan that she decided to undertake post-doctoral research in this field, relocating to the UK to join the laboratory of Professor Wolf Reik at the Babraham Institute in Cambridge.

Heather’s focus at Babraham was on epigenetic control of embryonic stem cells. During this time, she developed ground-breaking new experimental techniques that can assess genetic regulation in individual cells.

This achievement positioned her as a pioneer and world leader in the field of single-cell epigenomics.

Upon returning to Australia, Heather wanted to apply these new methods to cancer research and chose to study acute myeloid leukemia (AML), a rare but deadly blood cancer, as epigenetic processes are critical to its development and treatment.

In 2018, she received the $50,000 Metcalf Prize from the National Stem Cell Foundation of Australia in recognition of her early-career leadership in research.

Understanding how cancer cells adapt

The reason that cancers are so difficult to cure is that cancer cells can change over time and find new ways to survive and thrive despite ongoing anti-cancer treatment.

“In cancer cells, epigenetic processes are disrupted, meaning that genes aren’t well controlled,” explains Heather. “For example, genes important to control cell growth can be silenced by epigenetic changes in cancer cells. This allows cancer cells to grow in uncontrolled ways.”

This means cancer can come back, even after seemingly successful therapy. When this happens, treatments are no longer effective, and many patients pass away.

“My research is investigating these adaptive processes that help the cells to escape the effects of therapy”, Heather continues.  “And our findings suggest an increased dependence on cholesterol in these cells.”

She shares that the methods she’s developed generate incredibly rich data sets that are challenging to analyse. To overcome this, she’s worked in cross-disciplinary collaborations with theoretical physicists, statisticians and bioinformaticians. She’s also encouraged her research team to improve their data analysis skills.

Thanks to this persistence and with funding from the National Health and Medical Research Council, Cancer Institute NSW, and Cure Cancer Australia, Heather’s team has identified new treatment strategies that have potential to delay relapse in people living with blood cancer.

From the lab to improving lives

Heather’s research in blood cancer is expected to have a tangible impact on the lives of people living with cancer and their families within 10 years.

“Once we’ve validated treatment strategies to limit cancer cell adaptation and delay relapse, patients will benefit by enjoying a better quality of life and extended periods of remission. They’ll also be empowered to make informed decisions about their care.”

Other research projects Heather has contributed to have led to new treatment options and improved outcomes for people living with breast and blood cancers.

Her research has also advanced our global understanding of genetic regulation in many different aspects of biology, including neurobiology, fertility and regenerative medicine.

Her ground-breaking experimental techniques that allow the study of genetic regulation in individual cells are being used by researchers around the globe. The biotechnology industry is drawing on the methods she’s developed, creating analysis kits and services to aid research.

The biological insights gained using the methods she has developed will ultimately lead to new treatments for various disorders and advances in multiple industries.

Eradicating cancer recurrence together

To assist in their research, Heather’s research team works with a group of patient advocates with lived experience of rare blood cancers.

“We meet every other month to discuss ongoing projects and they help us to stay focused on the needs of people living with cancer by asking questions and sharing their experiences. They also encourage the research team by reminding us of how important our work is.”

Anyone interested in becoming a patient advocate should email Heather at heather.lee@newcastle.edu.au

They also work with clinical haematologists and leukaemia researchers in Newcastle (Calvary Mater Hospital) and across Australia (Australasian Leukaemia and Lymphoma Group).

These partnerships allow them to access valuable patient samples and help them understand the clinical challenges in treating leukaemia patients.

Heather’s ultimate goal is to see a world where cancers don’t come back. Where a single course of treatment eradicates a patient’s cancer once and for all.

To achieve this goal, doctors need new tests to monitor how cancers change and treatments to block, target or reverse those changes. With her new techniques and love for thinking outside of the box, she’s helping make this a reality.