Navigation Links
PARP inhibitors may have clinical utility in HER2-positive breast cancers
Date:9/16/2012

PHILADELPHIA Poly (ADP-Ribose) polymerase (PARP) inhibitors, shown to have clinical activity when used alone in women with familial breast and ovarian cancers linked to BRCA mutations, may be a novel treatment strategy in women with HER2-positive breast cancers, according to the results of a study published in Cancer Research, a journal of the American Association for Cancer Research.

Currently, women with HER2-positive breast cancers are treated with therapies that target HER2. However, many women with this form of cancer either fail to ever respond to these targeted therapies or initially respond to them but then become resistant to their effects.

"Until now, PARP inhibitors have been shown to exhibit single agent activity only in tumors that are deficient in DNA repair, such as familial breast and ovarian cancers that are linked to BRCA mutations," said Eddy S. Yang, M.D., Ph.D., assistant professor in the department of radiation oncology at the University of Alabama-Birmingham.

According to Yang, only about 5 to 10 percent of all breast and ovarian cancers are BRCA-associated familial cancers, so researchers are currently trying to expand the patient population that might benefit from PARP inhibitors, which are generally well tolerated and have relatively few side effects.

"To do that, we were attempting to render nonfamilial cancers deficient in DNA repair," he said.

In prior studies, the Yang lab found that inhibiting the epidermal growth factor receptor (EGFR) pathway, which is commonly overactive in many tumor types, resulted in a DNA repair defect similar to that seen in familial cancers. They subsequently showed that this "forced" DNA repair defect increased tumor sensitivity to PARP inhibitors. Because HER2 and EGFR are in the same family of proteins, Yang and colleagues theorized that HER2-targeted therapies might force a similar DNA repair defect in HER2-positive tumors, increasing their sensitivity to PARP inhibitors.

They found that HER2-positive breast cancer cell lines were indeed sensitive to PARP inhibitors, both in culture and when transplanted into mice.

"However, the surprise was that these HER2-positive tumors were sensitive to PARP inhibitors alone, independent of a DNA repair defect," Yang said. "This means that there may be other mechanisms, outside of DNA repair, that dictate the sensitivity of a tumor to PARP inhibitors."

The researchers hope to further map out the reason why HER2-positive tumors are sensitive to PARP inhibitors. If better defined, the knowledge could ultimately broaden the clinical application for PARP inhibitors.

"Our research suggested that inhibition of NF-kB signaling is a possible cause of this sensitivity, but there may be other determinants as well," Yang said. "If we are able to find the determinants of sensitivity, we may be able to extrapolate our effects to other tumor types."


'/>"/>
Contact: Jeremy Moore
jeremy.moore@aacr.org
215-446-7109
American Association for Cancer Research
Source:Eurekalert

Related medicine news :

1. Inhibitors of shuttle molecule show promise in acute leukemia
2. Preclinical data support ongoing clinical trials testing IDO inhibitors as a treatment for cancer
3. First targeted nanomedicine to enter human clinical studies
4. Clinical insight improves treatment with new lung cancer drug
5. Clinical news alert from the American Academy of Orthopaedic Surgeons
6. NYU Langone experts present research, clinical advances at neurosurgeons meeting
7. Kroenke honored for outstanding contributions in clinical research training
8. Awards celebrate clinical research that can improve health and alleviate suffering
9. Association for Psychological Science, SAGE launch Clinical Psychological Science
10. URMC clinical trial tests new regimen for hypertension
11. Analysis Finds Clinical Trials Often Small, of Poor Quality
Post Your Comments:
*Name:
*Comment:
*Email:
(Date:5/2/2016)... ... May 02, 2016 , ... MedaCheck, a leading medication ... outcomes, has announced its partnership with GrandView Health Services. , With decades of ... counter and prescription drug pharmacy services to thousands of residents. Serving Indiana, Ohio, ...
(Date:5/2/2016)... TN (PRWEB) , ... May 02, 2016 , ... ... and behavioral health services, today announced the opening of Twin Lakes Recovery Center. ... will be Summit’s first in the state. The residential facility is set ...
(Date:5/1/2016)... (PRWEB) , ... May 01, 2016 , ... Women's Excellence ... Essential Oils and taught by Patti Dolan, a Young Living Gold Member. , The ... 6:30pm - 7:15pm followed by a small intro to the Oils that can benefit ...
(Date:4/30/2016)... (PRWEB) , ... May 01, 2016 , ... Serenity Recovery, ... to rehabilitation, has produced a new video that focuses on one of the more ... recent sessions and clips from interviews with a participating patients and the Yoga class ...
(Date:4/30/2016)... , ... April 30, 2016 , ... ... Boise, President and CEO of EMED, today signed a multifaceted agreement which will ... and the Northern Caribbean University Department of Natural and Applied Sciences, Allied Health ...
Breaking Medicine News(10 mins):
(Date:4/28/2016)... April 28, 2016  Marking its one year ... and ovarian cancer risk test, Color Genomics ... genes that highly impact the most common hereditary ... the Color Test analyzes hereditary cancer risks for ... uterine cancers. The Color Test is physician ordered ...
(Date:4/28/2016)... YORK , April 28, 2016 ... online consumer insights on healthcare, announced today that it ... their report Cool Vendor in Life Sciences, 2016, ... April 15, 2016.  The report focuses on life-science- oriented ... gain insight from patients and doctors, confirm medication ingestion, ...
(Date:4/28/2016)... April 28, 2016 Oramed Pharmaceuticals Inc. ... pharmaceutical company focused on the development of oral drug delivery ... upcoming PIONEERS 2016 conference, presented by Joseph Gunnar ... New York . Nadav Kidron , ... conference. Presentation Details:   PIONEERS ...
Breaking Medicine Technology: