Genes may predict the need for further cancer treatments

A new predictive tool is being developed that could help patients with breast cancer and certain lung cancers decide whether follow-up treatments are likely to help.

Jerry Shay, PhD, vice chairman and professor of cell biology at University of Texas Southwestern in Dallas, led a 3-year study on the effects of irradiation in a lung cancer-susceptible mouse model. When his team looked at gene expression changes in the mice, then applied them to humans with early stage cancer, the results revealed a breakdown of which patients have a high or low chance of survival.

The findings, published online in Clinical Cancer Research (2014; doi:10.1158/1078-0432.CCR-13-2589), offer insight into helping patients assess treatment risk. Radiation therapy and chemotherapy that can destroy tumors also can damage surrounding healthy tissue. So with an appropriate test, patients could avoid getting additional radiation or chemotherapy treatment they may not need, Shay said.

"This finding could be relevant to the many thousands of individuals affected by these cancers and could prevent unnecessary therapy," said Shay. "We're trying to find better prognostic indicators of outcomes so that only patients who will benefit from additional therapy receive it."

Shay's study closely monitored lung cancer development in mice after irradiation. His group found some types of irradiation resulted in an increase in invasive, more malignant tumors. He examined the gene expression changes in mice well before some of them developed advanced cancers. The genes in the mouse that correlated with poor outcomes were then matched with human genes.

When Shay's team compared the predictive signatures from the mice with more than 700 human cancer patient signatures, the overall survivability of the patients correlated with his predictive signature in the mice. Thus, the classifier that predicted invasive cancer in mice also predicted poor outcomes in humans.

Shay's study looked at adenocarcinoma, a type of lung cancer in the air sacks that afflicts both smokers and nonsmokers. The findings also predicted overall survival in patients with early stage breast cancer and thus offer the same helpful information to breast cancer patients; however, the genes were not predictive of squamous cell carcinoma of the lung. Other types of cancers have yet to be tested.

The American Cancer Society estimates the risk of developing lung cancer to be 1 in 13 for men and 1 in 16 for women, including both smokers and nonsmokers. Lung cancer is the second most common cancer in both men and women, accounting for about 13% of all new cancers, and about 27% of cancer deaths. The American Cancer Society estimates more than 224,210 new cases of lung cancer and nearly 160,000 deaths from lung cancer will occur in 2014.

"Personalized medicine is coming," Shay said. "I think this is the future—patients looking at their risks of cancer recurrence and deciding what to do next. We can better tailor the treatment to fit the individual. That's the goal."

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