A new study from RCSI, conducted through the pioneering Precision Oncology Research Initiative for Metastatic Breast Cancer (PRISM) research programme, has identified a potential new way to slow the growth and spread of advanced hormone-positive breast cancer. 

The research is the first to show that a gene regulator known as CDK12 directly teams up with a hormone receptor and a key co-factor protein to drive cancer progression in difficult-to-treat breast cancers. The findings point to CDK12 as a promising new target for future therapies designed to stop breast cancer from spreading and becoming resistant to treatment.

This study is among the first to be published from the PRISM programme, a four-year initiative led by the Beaumont RCSI Cancer Centre to study the mechanisms that drive breast cancer’s spread. The programme is funded by Breast Cancer Ireland, the Research Ireland Strategic Partnership Programme, and Carrick Therapeutics, whose collaboration is central to translating PRISM’s scientific discoveries into future clinical applications.

“This discovery highlights a completely new pathway that we could potentially target to slow the progression of advanced ER+ breast cancer,” said Professor Leonie Young, RCSI Department of Surgery and joint senior author of the study.

“These findings are especially encouraging because they emerge from PRISM – a programme designed to unite leading academic researchers, clinicians and industry partners like Carrick Therapeutics to accelerate progress in cancer treatment and improve outcomes for patients.”

Towards better treatments

The researchers focused on breast cancers that are hormone receptor-positive, the most common subtype of the disease. Often, these cancers become resistant to treatment and spread to other parts of the body, including the brain.

By studying tumour samples from patients as well as laboratory models of advanced disease, the team discovered that the gene regulator CDK12 plays a critical role in driving aggressive growth in these cancers. When CDK12 was blocked using a new drug developed by Carrick Therapeutics, and now being investigated through the PRISM-Carrick collaboration, cancer cells were less able to grow and spread. This discovery is especially timely, as Carrick Therapeutics has recently advanced this drug into a first-in-human Phase 1 trial.

The study also found that high levels of CDK12 were associated with poorer survival, particularly in patients with hard-to-treat types of breast cancer.

“We’ve shown that CDK12 acts like a control switch, turning on genes that help breast cancer grow and spread,” said Dr Damir Varešlija, joint senior author.

“While more research is needed before these findings can be translated into clinical treatments, the study opens the door to new possibilities for tackling advanced breast cancer – particularly in patients who currently have limited treatment options” he added.

Aisling Hurley, CEO of Breast Cancer Ireland, said: “We are immensely proud to support research of this calibre through the PRISM initiative. Discoveries like this bring us one step closer to understanding and overcoming the mechanisms that drive treatment resistance in advanced breast cancer. It’s an excellent example of how collaboration between academia, clinicians, industry and patient-focused organisations can deliver real hope for patients and their families.”

The study led by Dr Daniela Ottaviani, Dr Damir Varešlija and Professor Leonie Young was published in the Journal of National Cancer Institute (JNCI). It was funded by Breast Cancer Ireland and Research Ireland with additional support from Enterprise Ireland, Breast Cancer Now and EU Interreg, and Carrick Therapeutics as a key collaborative industry partner driving translational impact within the PRISM programme.