RCSI researchers have identified a potential new way to slow the growth and spread of advanced hormone-positive breast cancer.
Published in the Journal of the National Cancer Institute, 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 was conducted through the pioneering Precision Oncology Research Initiative for Metastatic Breast Cancer (PRISM) research programme, a four-year initiative led by the Beaumont RCSI Cancer Centre to study the mechanisms that drive breast cancer’s spread, accelerate progress in cancer treatment and improve outcomes for patients.
The discovery highlights a new pathway that may be targeted to slow the progression of advanced ER+ breast cancer.
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 industry partner 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.
Further possibilities
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.
The researchers have shown that CDK12 acts like a control switch, turning on genes that help breast cancer grow and spread. 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.
The study was led by Dr Daniela Ottaviani and joint senior authors Dr Damir Varešlija and Professor Leonie Young. The programme is funded by Breast Cancer Ireland, the Research Ireland Strategic Partnership Programme, with additional support from Enterprise Ireland, Breast Cancer Now and EU Interreg, and Carrick Therapeutics, whose collaboration is central to translating PRISM’s scientific discoveries into future clinical applications.
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