Triple-negative breast cancer has been targeted by the National Cancer Institute as a key area for research.  About 20% of breast cancers are triple-negative.  These have higher recurrence and higher mortality than other breast cancers.  While most breast cancers can be treated with therapies that target the estrogen receptor (ER), progesterone receptor (PR) or the EGF2 receptor (HER2), triple-negative breast cancers lacks all 3 of these targets.  Nonspecific chemotherapy agents and surgery are also not sufficiently effective. Photodynamic therapy (PDT) utilizes photosensitizers (PS) to kill target cells. PS absorb light and create toxic reactive oxygen species. We are testing new porphyrin-derived PS on triple-negative breast cancer cells for their effectiveness in vitro. Our control is Foscan, which is currently in clinical trials. Our compounds show concentration-dependent killing in the light, with several showing high phototoxicity in the 1 �M range. They are less toxic in the dark than Foscan. The compounds show a wide range of affinities for MDA-MB231 cells. Surprising, several of the compounds with low uptake show high phototoxicity. The compounds also show a wide range of distribution coefficients and neither light nor dark toxicity correlates well with distribution coefficient. A major side effect of PDT agents is lingering skin photosensitivity. We tested the effect of light dose on phototoxicity for several of our PS which show varying levels of uptake and phototoxicity. We would like to find a combination of PS properties, PS concentration and light dose that kills at high light exposure but not at moderate exposure to minimize the side effects. Our results suggest that such a combination may be possible. Several of our compounds are effective at low concentration and may have properties superior to Foscan, which is toxic in the dark at concentrations near the therapeutic dose.

Modified porphyrins for photodynamic therapy of triple-negative breast cancer

247th National Meeting (2014)

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