It’s not all in their DNA: cancer cells with same genome can behave differently

16 December 2021
Man standing with folded arms, smiling at camera
Dr Shalin Naik brought his expertise in cellular barcoding
to the research collaboration, published in Nature.
For the first time, research has shown cancer cells with the same genetic blueprint won’t necessarily behave in the same way, with serious implications for how we target them.

A Peter MacCallum Cancer Centre (Peter Mac)-led study demonstrating these non-genetic changes in acute myeloid leukaemia cells was published in Nature.

The research team developed barcoding technology dubbed SPLINTR (Single-cell Profiling and LINeage TRacing) which helped the researchers to identify the unique genes expressed in each leukaemia cell, and monitor how this influences the cancer’s behaviour over time. They can then observe which acute myeloid leukaemia cells are most likely to form cancerous tumours.

Joint first author Dr Katie Fennell from Peter Mac said: “We developed a novel cellular barcoding technology that can track individual cancer cells over time and identify patterns that lead to different cell behaviour – even when the underlying genome is the same.”

Whilst this study was in acute myeloid leukaemia, the technology can be applied to many different cancers, presenting an opportunity to understand why some tumour cells survive drug treatment or relapse in specific organs.

Treatment resistance

WEHI scientist and study co-author Dr Shalin Naik brought his expertise in single cell systems biology and cellular barcoding to the project.

“Studying biology at the level of single cells is bringing fresh insights into normal development and cancer,” Dr Naik said.

“This was a really powerful example of where our lab’s experience with cellular barcoding could help inform longstanding questions in the study of cancer and therapy resistance in the Dawson lab.”

“Our jointly supervised PhD student Dr Fennel was able to successfully combine this to make these discoveries.”

Drug resistance and tumour recurrence are major barriers to the successful treatment of cancer, and often arise from rare populations of tumour cells, which can be difficult to monitor in the clinic. The study highlights the power of using SPLINTR to not only identify these rare tumour subpopulations, but also to find novel therapeutic targets and/or biomarkers to monitor them clinically.

Precision medicine

While all precision medicine aims to tailor treatment to the unique features present in a patient’s cancer, thus far these approaches have exclusively focused on the unique DNA mutations present.

However, recent studies show that up to 40 per cent of tumours that relapse after initially responding to treatment show no evidence of new gene mutations in the cancer cells to account for this therapy resistance.

“This work challenges the dogma that precision medicine is just about finding new genetic mutations,” said Peter Mac senior author Professor Mark Dawson.

The study highlights the importance of broadening the ambition of precision medicine beyond just surveying a patient’s DNA mutations.

“This is only one side of the coin. We urgently need to understand and develop treatments to also counter the non-genetic factors that influence cancer cell behaviour,” said joint first author Dr Dane Vassiliadis from Peter Mac.

The research was led by Peter Mac, in collaboration with academic partners at The University of Melbourne, WEHI, the Victor Chang Cardiac Research Institute and UNSW.

Written with Peter MacCallum Cancer Centre (see media release

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