Researchers at the Institute of Cancer Research in London have identified that suppressing the activity of an enzyme named G9a can stop tumor cells from entering a dormant state, which often helps breast cancer drugs lose their effectiveness. The new findings were published in Cancer Discovery (CD) and are triggering renewed interest in how to counter drug resistance in breast cancer treatment.
The focus of the study centers on estrogen receptor positive (ER+) breast cancer. In this form of cancer, malignant cells display estrogen receptors, the hormones that normally help regulate growth and development. When these receptors are present, estrogen can accelerate the reproduction of cancer cells and fuel tumor growth. ER+ breast cancer represents a sizable portion of diagnosed cases and is known for a relatively high rate of recurrence after initial treatment.
Researchers explain that ER+ tumors can adopt a strategy similar to dormancy, in which cancer cells temporarily reduce their activity. This dormancy allows malignant cells to dodge targeted therapies and immune system surveillance, later reigniting disease progression even after therapy appears to have been successful. Dormant cells can disseminate from the primary tumor and settle in distant tissues as micrometastases, posing a persistent challenge for clinicians aiming to achieve long-term remissions.
Through their experiments, the scientists demonstrated that G9a also plays a key role in triggering this dormant behavior. When G9a activity is lowered, tumor cells lose their sleep-like state, becoming more vulnerable to treatment. In estrogen-positive breast cancer models, reduced G9a activity not only prevents dormancy but can also help eradicate cells more effectively when combined with hormonal therapies. This has the potential to enhance the overall efficacy of existing treatment regimens and reduce the likelihood of relapse.
The team notes that these insights could inform the development of new therapeutic approaches. By targeting G9a alongside standard endocrine therapies, it may be possible to prevent cancer cells from hiding in plain sight and to improve patient outcomes, especially for those with ER+ disease. The implications extend to the broader strategy of integrating epigenetic targets with hormonal blockade to overcome resistance mechanisms commonly observed in breast cancer care. Researchers anticipate that further studies will validate these findings in clinical settings and help translate them into practical treatment options for patients. (Attribution: Cancer Discovery, 2024)
In addition to these findings, the research adds to a growing body of evidence that epigenetic regulators influence tumor behavior and treatment response. G9a, a histone methyltransferase, has emerged as a promising therapeutic target in various cancers because of its role in controlling gene expression patterns that determine cell fate. By refining our understanding of how G9a orchestrates dormancy, scientists can design strategies that prevent cancer cells from evading therapy, thereby improving the durability of responses to endocrine treatment. The study also underscores the importance of a personalized approach to breast cancer, where molecular features such as ER status guide the choice of combination therapies that best counter dormancy and recurrence. (Attribution: Cancer Discovery, 2024)