Many cancer therapies target specific proteins that proliferate on the outside of some cancer cells, but the therapies are imperfect and the cancer does not always respond. Since it is beneficial for doctors to know as soon as possible how a cancer is affected by treatment, researchers from Vanderbilt University are striving to design tests that assess treatment response rapidly, accurately, and cost-effectively. The team has demonstrated a new way to optically test cultured cancer cells' response to a particular cancer drug. The results appear in the December issue of the Optical Society's (OSA) open-access journal Biomedical Optics Express.
Certain cancer cells display a higher-than-normal number of proteins called human epidermal growth factor receptor 2 (HER2). In healthy cells, HER2 helps mediate cell growth, but overexpression of HER2 can mark one of the most aggressive forms of breast cancer. Drugs that bind to and block growth factor receptors have been shown to prolong life in some cancer patients, but about 30 percent of HER2 overexpressing tumors do not respond to the drug. Tests to identify these non-responding tumors early on would help doctors make important treatment decisions that could improve patient outcomes.
To design such a test, the Vanderbilt team took advantage of the fact that some cancer cells preferentially use a different metabolic pathway when compared to normal cells. The researchers visualized the relative use of the different pathways by shining the cells with frequencies of light that caused two different metabolic molecules to naturally fluoresce. They then calculated a ratio between the two levels of fluorescence, called an optical redox ratio. The team found that, of the different cell lines they tested, HER2 overexpressing cells had the highest optical redox ratio. They also found that when HER2 cancer cells were treated with an HER2-blocking drug, the ratio decreased. This decrease, however, was not observed in cancer cells that were resistant to the drug. The findings lay the groundwork for future in vivo studies and hold the promise that real-time tumor response to treatment might be measured optically.
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Paper: "Optical imaging of metabolism in HER2 overexpressing breast cancer cells," Biomedical Optics Express, Vol. 3, Issue 1, pp. 75-85 (2012).