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Scientists identify genes responsible for resistance to tamoxifen

September 14th, 2016

Scientists may have unlocked the genetic code that determines why many patients with estrogen receptor-positive breast cancer fail to respond to the widely used drug tamoxifen, a response known as endocrine resistance.

Patients who have higher levels of certain genes, such as XPO, are more likely to be resistant to tamoxifen which means they will develop incurable metastatic cancer.

However, if tamoxifen is combined with the drug selinexor, which inhibits the activity of XPO, patients’ sensitivity to tamoxifen is enhanced and breast tumours don’t return, according to a new study from the University of Illinois.

The researchers identified a ‘gene signature’ which could help clinicians predict which patients are likely to be endocrine resistant and choose alternative treatments that may achieve better outcomes for their patients.

Estrogen receptor-positive breast cancer accounts for about 70 per cent of breast cancers. In these forms of the disease, the nuclei in patients’ breast cells overproduce a protein that binds with and grows in response to estrogen. Tamoxifen, an endocrine therapy that has been widely used since the 1970s, blocks this binding process, constraining the growth and dissemination of the cancer cells.

However, up to one-third of patients with hormone-responsive breast cancer don’t respond efficiently or eventually stop responding to tamoxifen.

While tamoxifen is still very effective compared with other endocrine-targeting agents, determining which patients will respond effectively has perplexed doctors and researchers for some time.

Selinexor is currently in clinical trials for treating leukaemia and therapy-resistant prostate cancer, and is well tolerated, with patients experiencing very mild side effects that wear off as therapy continues.