Triple negative breast cancers
(lacking Estrogen, Progesterone and HER2 receptor expression) constitute
approximately 15% of breast cancers.
Unlike Estrogen receptor positive and HER2 positive cancers, there are
currently no targeted therapies for triple negative breast cancers,
necessitating treatment with cytotoxic drugs.
Furthermore, the acquisition of multi-drug resistance limits the effect
of cytotoxic chemotherapeutics.
Identifying new therapies for
triple negative cancers lacking the adverse effects of cytotoxic therapy is an
important goal, but conventional drug discovery is expensive and
time-consuming. The “repurposing” of
existing drugs is an attractive alternative, as a wealth of preclinical and
clinical data is already available, greatly reducing the time and resources
required to bring a candidate drug to clinical trial.
The Johns Hopkins Clinical
Compound Library, containing approximately 1,500 clinical compounds, was used
to screen a multi-drug resistant, triple negative breast cancer cell line,
MDA16, for drug sensitivity.
Primary screening identified 30
compounds with antiproliferative/cytotoxic activity, including antifungals,
antibiotics and antimalarials. Secondary
screening confirmed the sensitivity of MDA16 cells to 13 of 18 (72%) selected
compounds. Additional work has
determined the sensitivity of other breast cancer and colorectal and prostate
cancer cell lines to selected drugs and examined mechanisms of action.