Approximately 1 in 8 women in the US will suffer from breast cancer.  While most breast cancers can be treated with standard chemotherapy or with therapies that target the estrogen receptor (ER), progesterone receptor (PR) or the EGF2 receptor (HER2), almost 1 in 5 breast cancers lacks all 3 of these targets, making them triple-negative.  Triple-negative breast cancers recur more often and have higher mortality than other breast cancers- current treatments are not effective.  Photodynamic therapy (PDT) is a cancer treatment that utilizes photosensitizers (PS) which are compounds that absorb light and create reactive oxygen species that kill the cell.  We are testing new porphyrin-derived PS for toxicity on triple-negative breast cancer cells to determine if they are potentially useful for treating triple-negative breast cancer.  We are comparing our compounds to Foscan, which is currently being used in clinical trials.  Our PS show concentration-dependent killing at low concentrations in the light, with several killing well in the 1-3 �M range.  They show reduced toxicity in the dark compared to Foscan.  We compared how well the compounds are taken up by MDA-MB231 cells.  Surprising, several of the compounds show high toxicity despite low uptake.  Unwanted toxicity to skin at moderate light doses is one of the side effects of PDT agents.  We tested the effect of light dose on phototoxicity, looking for combination of porphyrin concentration and light dose that kill at high light exposure but not at moderate exposure.  Our results suggest such a combination may be possible.  Several of our compounds compare favorably to Foscan, killing cells at low concentration, and may have some properties that are superior to those of Foscan, which is toxic in the dark at low doses.

In vitro photodynamic therapy of triple-negative breast cancer cells

247th National Meeting (2014)

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