Understanding the origins of breast cancer by mapping gene mutations and cancer switches

Funded by Mother’s Day Classic Foundation (MDC)

Dr Stephin Vervoort is a Lab Head (Vervoort Lab) at WEHI in the Epigenetics and Development Division.

The challenge:

Breast cancer develops and grows as a result of changes in our DNA.

When a breast tumour is analysed using DNA sequencing technologies, it is common to find hundreds of gene changes (mutations) compared to normal breast cells. However, it is extremely difficult to tell which of these mutations ‘drive’ cancer growth and which ones are ‘harmless passengers’ in the tumour. This uncertainty makes it harder to understand what truly drives breast cancer, which in turn limits how accurately we can diagnose the disease, predict how it will behave, and choose the most effective treatments for each person.

Cancer cells also rely on specific cellular switches (kinases) that keep them alive. More than 500 kinases exist, but only a few have been well-studied to date. Understanding which kinases are essential to the survival of different types of breast cancer, and how they interact with the ‘driver’ gene mutations, offers new opportunities to develop better targeted treatments for breast cancer.

Project description:

Dr Stephin Vervoort’s Pink Sky Grant project, funded by the Mother’s Day Classic Foundation (MDC), will use a powerful gene-editing platform that he and his team have developed to recreate real mutations found in breast tumours.

Instead of testing every mutation one by one, the team will use this platform to recreate the same hundreds of mutations that naturally occur in tumours at scale, quickly and systematically into healthy breast cells. This allows them to observe which mutations push healthy cells towards becoming cancerous. A consumer advisor involved in the project compares this approach to a hacker rapidly testing many password combinations at once rather than one at a time – a powerful way to discover which mutations ‘unlock’ cancer development.

But understanding cancer drivers is only part of the challenge. The research team will also use a new technology that can precisely silence every one of the more than 500 kinases systematically to identify which ones breast cancer cells rely on to survive and grow, and therefore could make good drug targets in the future.

Potential impact:

If successful, Dr Vervoort’s Pink Sky Grant project could transform how breast cancer is understood and treated by revealing the key gene mutations and cancer ‘switches’ that drive the disease. By creating a detailed atlas of cancer‑causing mutations and the kinases that help tumours survive, Dr Vervoort and his team could identify new weaknesses in breast cancer cells that can be targeted with future therapies.

The knowledge gained from this project could guide future tools to help clinicians identify the driver mutations that matter most in a person’s tumour to better understand how people may respond to therapies. The findings may also reveal new therapeutic targets, enabling more personalised and effective treatments that could improve outcomes for people affected by breast cancer.

Grant code: 2025/PS0114
Active years: 2026-2029
Scientific project title: Systematic Deconstruction and Reconstruction of Breast Cancer: A Comprehensive Driver and Kinome Atlas