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How breast cancer cells evade therapeutic attacks
Date:3/31/2010

Tumour cells depend upon estrogens to survive and proliferate in about 70% of all breast cancer cases. The most frequently used treatment to fight this variety of tumours relies on anti-estrogens such as tamoxifen. However, resistance to this type of therapy develops in more than 30% of the patients. Understanding the mechanisms involved in the appearance of resistance to tamoxifen is thus essential to develop new therapeutic approaches. The research done by the team of Didier Picard, professor at the University of Geneva (UNIGE), provides key answers in the 1st of April 2010 edition of Genes & Development. Their study reveals how cancer cells become impervious to the drug by activating a specific biochemical cascade. The latter, normally triggered by a chemical messenger called cyclic AMP, is permanently stimulated in cells refractory to the treatment.

Breast cancer, which is characterized by an enhanced and anarchic proliferation of mammary cells, is one of the main causes of cancer-related mortality in women. In over two thirds of the cases, estrogens play an active part in the progression of the disease, due to the presence of receptors for this hormone in the nucleus of malignant cells. Estrogens indeed modulate the expression of genes necessary to cell survival and proliferation through their interaction with these receptors.

The most frequent treatment for this type of breast cancer, called hormone-dependent, relies on anti-estrogens such as tamoxifen, which block tumour cell growth by inhibiting the activity of the receptor. However, the cancer eventually becomes resistant to the therapy in more than 30% of the patients.

The second messenger's key role

"Estrogen receptors, notably the one called ERα, are also activated by other molecules that operate in an indirect way, without interacting with them", explains Didier Picard, professor at the Faculty of Sciences of UNIGE. "We aim precisely at understandin
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Contact: Laura Pizurki
Lara.Pizurki@unige.ch
Cold Spring Harbor Laboratory
Source:Eurekalert

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