Researchers identify existing drug’s potential for triple negative breast cancer

Researchers at The Institute of Cancer Research, London (ICR) have identified an already approved breast cancer drug which could have promise in the treatment of triple negative breast cancer (TNBC).

The study, funded by research and care charity Breast Cancer Now, suggests that palbociclib – marketed by Pfizer as Ibrance – could be used to treat around a fifth of people with TNBC.

The research discovered a way to identify TNBC tumours that could be more likely to respond to CDK4/6 inhibitors such as palbociclib.

To do this, the research team screened 200 of the most frequently altered genes in breast cancer, to evaluate how changes in these genes affect a cancer’s ability to grow.

The ICR researchers found that TNBC cells with alterations that caused a reduction in the levels of the CREBBP protein could grow more aggressively and at a faster rate.

Using two large patient databases to further investigate the role of low CREBBP tumour levels, the team also found that this is linked to poorer survival for TNBC patients.

In addition, low levels of CREBBP also occurs in a number of other cancers including uterine, ovarian and some lung and bladder cancers – suggesting the vital role it plays in tumour development or growth.

Crucially, the researchers found that when the levels of this protein are low, tumour cells change how they multiply by instead relying on the proteins CDK4 and CDK6 – these can be blocked by CDK4/6 inhibitors.

Currently, palbociclib is used in the UK to treat some secondary or metastatic breast cancers. The research team tested the effectiveness of this drug in cancer cells with CREBBP alterations in the lab and in mice.

They found that the drug was effective, even when tested on standard chemotherapy-resistant TNBC cells that lacked CREBBP.

“Our study shows what drives the growth of some triple negative breast cancers and suggests the exciting possibility that an already-approved breast cancer drug could be used to help women with this type of disease,” said Rachael Natrajan, Team Leader in Functional Genomics at The Institute of Cancer Research, London.

“Our findings were only possible because we used an innovative model, involving the growth of 3D ‘mini tumours’ in the lab, to more closely reflect how tumours develop in the body,” she added.