Study Uncovers Key Cause of Breast Cancer Treatment Resistance

Researchers in Australia have uncovered a previously unknown mechanism that may explain why some breast cancers become resistant to treatment.

The study, published in Nature, found that the retinoblastoma (Rb) protein, which is widely known for suppressing cancer growth, can also activate genes linked to the hormone estrogen. Some of these genes may help cancer cells survive treatment and retain their ability to regrow, according to the Peter MacCallum Cancer Centre.

The research team found that Rb does more than suppress genes responsible for cell division. It can also activate biological pathways that partially counteract its cancer-fighting effects, said Associate Professor Shom Goel, the study’s senior author.

The findings may help explain why CDK4/6 inhibitors work particularly well when combined with endocrine therapy in hormone receptor-positive breast cancer, the most common form of the disease.

CDK4/6 inhibitors activate Rb to prevent cancer cells from dividing, while endocrine therapy blocks estrogen-driven signals that Rb can also trigger. The two treatments therefore allow Rb’s tumour-suppressing effects to remain dominant, Goel said.

However, when breast cancers develop resistance to endocrine therapy, the estrogen-related gene programme can remain active despite treatment. This may reduce the effectiveness of CDK4/6 inhibitors, the researchers found.

“Understanding this previously unknown role of Rb gives us an important new way to think about drug resistance,” Goel said.

The researchers said the discovery could help guide the development of new combination therapies designed to overcome treatment resistance, prolong the effectiveness of existing medicines and improve outcomes for breast cancer patients.