New hope for hormone resistant breast cancer

A new finding provides fresh hope for the millions worldwide with oestrogen receptor positive breast cancer. Australian scientists have shown that a specific change, which occurs when tumours become resistant to anti-oestrogen therapy, might make the cancers susceptible to treatment with chemotherapy drugs.

Seventy percent of breast cancer patients have oestrogen receptor positive cancer, and most patients respond well to anti-oestrogen therapies, for a few years at least. Within 15 years, however, 50% will relapse and eventually die from the disease.

Dr Andrew Stone, Professor Susan Clark and Professor Liz Musgrove, from Sydney’s Garvan Institute of Medical Research, in collaboration with scientists from Cardiff University, have demonstrated that the BCL-2 gene becomes epigenetically ‘silenced’ in resistant tumours. This process is potentially detectable in the blood, providing a diagnostic marker. Their findings are now online in the international journal Molecular Cancer Therapetics.

Epigenetics involves biochemical changes in our cells that directly impact our DNA, making some genes active, while silencing others. Epigenetic events include DNA methylation, when a methyl group - one carbon atom and three hydrogen atoms - attaches to a gene, determining the extent to which it is ‘switched on’ or ‘switched off’.

Dr Stone and colleagues have shown in human disease, as well as in several different cell models, that BCL-2 is silenced in oestrogen-resistant tumours by DNA methylation.

“The main purpose of the BCL-2 gene is to keep cells alive, so when the gene is silenced, cells become more vulnerable to chemotherapy,” said Dr Stone.

Breast and prostate cancers are the most common malignant disease in female and male world population, respectively. Both of these tumors are predominantly hormonal-dependent, what is rationale for the widely used endocrine treatment, with specific approach in each of them. Although endocrine treatment is obviously effective and responsible for prolonged progression-free survival and even survival, the problem is that breast and prostate cancers inevitably become "hormone-resistant". The paradigm of treatment has to be changed and today there are some ways to overcome these lack of endocrine responsivness. It is known better today which mechanisms are involved in hormone-resistance, and they are numerous, so the designation of new drugs with key features necessary activity in hormone-resistant tumors. In breast cancer, there are selective estrogen modulators as a way to overcome this problem; there is also a combination of receptor-tyrosine kinase and hormonal treatment documented as active in such cases.

On the other hand, abirateron-acetat and enzalutamide as a new androgen-receptor-signalling inhibitors proved that androgen signalling cascade is still active even in a castration-resistant prostate cancer.

B reast- and prostate cancer are two the most common invasive cancers in women and men, respectively. Although these tumors seem to be considerably different due to diverse anatomical and physiological features of the organs where they arise, they share a common feature of "hormonal-dependence". Both of organs require gonadal steroids for their development and tumors arising from them have remarkable underlying biological similarities. Recently, it has been made a great improvement in our understanding of the pathophysiology of breast and prostate cancers which paved the way for new treatment strategies.