Olaparib shows promise in treating ovarian cancer, even without BRCA mutations

August 21, 2011, Lancet

The PARP inhibitor, olaparib, that has shown promise in women with an inherited mutation in their BRCA1 or BRCA2 gene (accounting for about 5-10% of breast and ovarian cancer cases), has, for the first time, been shown to reduce the size of tumours in a much wider group of ovarian cancer patients without these BRCA gene mutations. The findings, published Online First in The Lancet Oncology, highlight the potential of olaparib to treat patients with more common sporadic (non-hereditary) tumours and could offer a new treatment option for one of the most deadly cancers in women.

"Olaparib represents a promising therapeutic option for patients with this aggressive malignant disease for whom treatment options are limited to toxic chemotherapies", explains lead author Karen Gelmon from the BC Cancer Agency, Vancouver, Canada.

Olaparib works by blocking the activity of a protein called Poly (ADP ribose) polymerase (PARP). Both PARP and BRCA proteins are involved in DNA repair. Inhibiting PARP in a tumour that already lacks a BRCA gene prevents from repairing their DNA (enhancing the effectiveness of DNA-damaging ) and causes them to die—a process known as synthetic lethality.*

Until now, whether olaparib could also be effective in a broader group of sporadic breast and ovarian cancers that might share similar DNA repair deficiencies, such as triple-negative breast cancer and high-grade serous ovarian cancer, was not known.

The phase 2 trial was designed to evaluate the drug's effectiveness in the treatment of breast and ovarian cancer without mutations. Between July, 2008, and September, 2009, 92 patients (65 with ovarian cancer and 26 breast cancer) were given olaparib 400 mg twice daily for 4 weeks, and classified according to their BRCA1 and BRCA2 mutation status.

Among women with ovarian cancer, 41% with BRCA mutations showed a substantial shrinkage in the size of their tumours compared with 24% of patients without mutations. None of the patients with breast cancer had an objective response.

Olaparib was generally well tolerated and most side effects were mild, including fatigue, nausea, vomiting, and decreased appetite. The authors conclude: "New treatments targeting mechanisms seem to provide new hope for treatment of ovarian cancer."

In a Comment, Melinda Telli from Stanford University School of Medicine, California, USA discusses the potential of this new class of genetically-targeted drugs and remarks: "For the first time, activity of a PARP inhibitor as monotherapy in women with advanced high-grade serous ovarian cancer who do not have a germline or BRCA2 mutation [has been shown]. This finding not only suggests new therapeutic possibilities for women with this aggressive type of , but also importantly confirms the hypothesis that subpopulations of patients with common sporadic tumours can be targeted effectively with PARP inhibitor therapy."

More information: Paper online: www.thelancet.com/journals/lan … (11)70214-5/abstract

Related Stories

Recommended for you

Single blood test screens for eight cancer types

January 18, 2018
Johns Hopkins Kimmel Cancer Center researchers developed a single blood test that screens for eight common cancer types and helps identify the location of the cancer.

Researchers find a way to 'starve' cancer

January 18, 2018
Researchers at Vanderbilt University Medical Center (VUMC) have demonstrated for the first time that it is possible to starve a tumor and stop its growth with a newly discovered small compound that blocks uptake of the vital ...

How cancer metastasis happens: Researchers reveal a key mechanism

January 18, 2018
Cancer metastasis, the migration of cells from a primary tumor to form distant tumors in the body, can be triggered by a chronic leakage of DNA within tumor cells, according to a team led by Weill Cornell Medicine and Memorial ...

Modular gene enhancer promotes leukemia and regulates effectiveness of chemotherapy

January 18, 2018
Every day, billions of new blood cells are generated in the bone marrow. The gene Myc is known to play an important role in this process, and is also known to play a role in cancer. Scientists from the German Cancer Research ...

These foods may up your odds for colon cancer

January 18, 2018
(HealthDay)—Chowing down on red meat, white bread and sugar-laden drinks might increase your long-term risk of colon cancer, a new study suggests.

The pill lowers ovarian cancer risk, even for smokers

January 18, 2018
(HealthDay)—It's known that use of the birth control pill is tied to lower odds for ovarian cancer, but new research shows the benefit extends to smokers or women who are obese.


Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Click here to reset your password.
Sign in to get notified via email when new comments are made.