Paragazole excels in preclinical models of triple-negative breast cancer

No ER, PR or HER2? New drug, paragazole, excels in tests of triple-negative breast cancer. Image: Flickr/estetika

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 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.

add to favorites email to friend print save as pdf

Related Stories

New target, new drug in breast cancer

Jun 04, 2012

Many breast cancers depend on hormones including estrogen or progesterone for their survival and proliferation. Eight years of lab work at the University of Colorado Cancer Center and elsewhere suggest that the androgen (AR) ...

Drug shows promise for triple-negative breast cancer

Jul 03, 2012

(Medical Xpress) -- A promising new therapy for hard-to-treat triple-negative breast cancer has been reported in the journal Breast Cancer Research by a team at the Tulane University School of Medicine, led by ...

Clinical trial hits new target in war on breast cancer

Dec 03, 2012

Breast cancers are defined by their drivers – estrogen and progesterone receptors (ER and PR) and HER2 are the most common, and there are drugs targeting each. When breast cancer has an unknown driver, it also has fewer ...

Trio of drugs may combat 'triple negative' breast cancer

Dec 10, 2010

A gene target for drug resistance, a triple-drug cocktail for triple negative breast cancer, and patients' risk for carpal tunnel syndrome are among study highlights scheduled to be presented by Johns Hopkins Kimmel Cancer ...

Recommended for you

New clinical trial launched for advance lung cancer

7 minutes ago

Cancer Research UK is partnering with pharmaceutical companies AstraZeneca and Pfizer to create a pioneering clinical trial for patients with advanced lung cancer – marking a new era of research into personalised medicines ...

Physicians target the genes of lung, colon cancers

17 hours ago

(Medical Xpress)—University of Florida physicians and researchers are collaborating to map the genes of different types of cancer, and then deliver medication to attack cancer at its source.

User comments