Trinity find may help defeat cancer drug resistance

Irish researchers have discovered a molecule that could improve targeted treatments for breast cancer and a number of other cancers.

Scientists at Trinity College Dublin believe the new biomarker could be the key to overcoming resistance to drugs such as Herceptin, which targets HER2 positive cancers.

HER2 positive breast cancer tends to be more aggressive than other types of breast cancer and is also less responsive to hormone treatments.

Researchers, led by Prof Lorraine O’Driscoll from TCD’s School of Pharmacy and Pharmaceutical Sciences, discovered a molecule called Neuromedin U (NmU).

NmU is strongly associated with resistance to the new anti-cancer drugs for HER2 positive cancers.

The discovery suggests NmU could be used as a biological marker to indicate the likelihood of responsiveness in a particular patient. It may also be very important in the management of resistance to these drugs.

Their findings are published in the leading international peer-reviewed journal — Cancer Research, the most frequently cited cancer journal in the world.

Herceptin specifically targets HER2, kills these cancer cells and decreases the risk of recurrence.

About one-in-four breast cancer patients are HER2 positive. In such cases the protein HER2 is found in greater amounts on cancer cells compared to normal cells and is associated with a poorer prognosis for the patients.

However, in recent years a new range of targeted anti-cancer drugs have become available to treat patients with HER2 positive breast cancer and some other cancers such as HER2 positive gastric cancer.

The best known drug is Herceptin (trastuzumab), but there are other newer drugs in this family, including lapatinib, neratinib, afatinib, pertuzumab and T-DM1.

“Many patients with HER2 positive tumours gain huge benefits from these drugs.

“Unfortunately, however, some who seem suitable candidates based on a HER2 test don’t gain the maximum intended benefit from these treatments,” said Prof O’Driscoll. “They may have a natural level of resistance to the treatment which is not detectable with currently available tests.”

Prof O’Driscoll said clinicians urgently need ways of predicting which patients with HER2 tumours are likely to gain real benefit.

“Our discovery may offer a new way to predict or identify both innate and acquired resistance, overcome it and potentially block or prevent resistance,” she said.

The research team conducted other studies which found that blocking NmU also significantly slowed tumour growth in the body and they plan to conduct further studies in this area.

Red meat risks

Eating a large amount of red meat in early adulthood could be associated with an increased risk of breast cancer.

Substituting red meat with legumes — such as peas, beans, and lentils — nuts, poultry, and fish could reduce the risk, according to new research.

Studies have found no significant association between the consumption of red meat and breast cancer, but the team of US researchers said most previous research has been based on diet during mid and later life.

So they decided to assess the dietary habits of 89,000 pre-menopausal women aged 26 to 43, in 1991.

Their study, published on bmj.com, examined frequency of red meat intake as well as other foods through a food frequency questionnaire. The authors also assessed the women’s adolescent food intake.

In the 20-year follow-up period, medical records identified 2,830 cases of breast cancer.

The researchers estimated that for each step-by-step increase in women’s consumption of red meat, there was a step-by-step increase in the risk of getting breast cancer.

Higher intake of red meat was associated with a 22% increased risk of breast cancer overall.

And each additional serving per day of red meat was associated with a 13% increase in risk of breast cancer.

Substituting one serving of red meat each day of combined legumes, nuts, poultry, and fish was associated with a 14% lower risk of breast cancer

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