Paragazole excels in preclinical models of triple-negative breast cancer

Breast cancers that lack estrogen receptors are more difficult to treat than ER+ cancers. Research presented at the AACR Annual Meeting 2013 demonstrates an investigational drug, Paragazole, that makes triple-negative breast cancer cells express estrogen receptors, and that increases the sensitivity of these cells to chemotherapy.

"Basically what we're trying to do is use triple-negative breast cancer models to develop targeted drugs for treatment. Paragazole is an especially exciting candidate," says Jennifer Diamond, MD, investigator at the University of Colorado Cancer Center and medical oncologist at the University of Colorado Hospital.

Paragazole is a novel histone deacetylase (HDAC) inhibitor developed at CU Boulder in the laboratories of Xuedong Liu and Andy Phillips, being tested at the CU Cancer Center. In this study, Diamond and colleagues tested the drug against a range of breast cancer cell lines with and without combination with chemotherapies paclitaxel, gemcitabine or carboplatin. Interestingly, it was specifically the cell lines that didn't express estrogen – the aggressive, triple-negative cells – that were most affected by paragazole. Sure enough, the researchers saw increased expression of CARM1 mediated estrogen receptors in these especially sensitive cells.

It was as if paragazole set up these triple negative cells so that chemotherapy could be more effective.

"This really is a case in which the result was greater than the sum of its parts. Paragazole with chemotherapy was more effective than the combined effects of both drugs, alone," Diamond says.

Studies with the drug are continuing with the eventual goal of moving the therapy from the lab to the clinic in selected patients.