PARP Inhibitors in Breast Cancer Treatment and Clinical Trials

What role may PARP inhibitors play in breast cancer treatment?. Image © Nagashima, T., Hayashi, F., Yokoyama, S., RCSB Protein Data Bank

What role may PARP inhibitors play in breast cancer treatment?  Several drugs known as PARP inhibitors have been studied recently for the treatment of breast cancer.  What does this category of medications do, and what may be their eventual role in the management of people with breast cancer?

About PARP and DNA Repair

PARP is an acronym for poly (ADP-ribose) polymerase. PARP is a protein that has several roles in cellular processes, most notably in DNA repair and programmed cell death (apoptosis).

Healthy cells can use PARP to repair themselves and live out their normal life cycle. But cancer cells may also use PARP to repair DNA damage, thus extending their uncontrolled growth. Such cancers can become resistant to treatment. There are several different PARP proteins, and they each have their own role in functions within cells.

PARP Inhibitors And Breast Cancer Treatment

A PARP inhibitor is a drug that blocks PARP proteins from performing their roles in repairing damaged cancer cells. Chemotherapy and radiation work by breaking the DNA of cells so that they may not reproduce. Some types of cancer cells use PARP enzymes to repair their DNA damage and recover from the assault of cancer treatments. Several clinical trials are being done to see if PARP inhibitors, in combination with other cancer treatments, can block PARP protein from damaged cancer cells.

Effects On Breast Cancer Cells

If a PARP inhibitor is added to chemotherapy treatments for breast cancer, researchers hope cancer cells that have resisted anticancer drugs will be become vulnerable to fatal DNA damage.

In some cases, a PARP inhibitor may be used alone, rather than in conjunction with chemo and radiation. Even better news is that PARP inhibitors do not appear to affect normal, non-cancerous cells. That means fewer side effects for patients and faster recovery from treatments.

Hope for Hereditary Breast Cancers

PARP inhibitors may be especially helpful for patients with hereditary breast cancer.

People who have BRCA1 and BRCA2 genetic mutations are at very high risk for developing breast cancer. Healthy BRCA genes produce proteins that can suppress tumor formation (they are called tumor suppressor genes), but mutated BRCA genes are powerless in making these proteins that fight against cancer cells. PARP inhibitors may exploit the weakness inherent in cancer cells with mutated BRCA. One possible use for PARP inhibitors may be prevention of hereditary breast cancer. Perhaps PARP inhibitors will become a preventative treatment for high-risk women and would make prophylactic mastectomies obsolete.

Encouraging News for Triple-Negative Breast Cancers

A few clinical trials of PARP inhibitors have found some clinical benefit from adding a PARP inhibitor to other treatments for metastatic triple negative breast cancer.  In these studies, the PARP inhibitors were well tolerated.  At this time the only approved targeted therapy for metastatic breast cancer is bevacizumab, but this drug does not have much specific benefit for people with triple-negative breast cancer.

Other Uses For PARP Inhibitors

Drugs developed with PARP inhibitors are being tested on several kinds of cancer: breast and ovarian, uterine, brain, and pancreatic.  In 2015, a PARP inhibitor was approved for the treatment of some ovarian cancers.

Potential Importance of PARP Inhibitors

The addition of PARP inhibitors to the current arsenal of weapons against breast cancer looks very promising. PARP inhibitors increase the effectiveness of chemotherapy against aggressive hereditary and triple-negative breast cancers, potentially without adding many serious side effects. These drugs appear to improve quality of life as well as extend survival for patients. Fighting breast cancer at the level of its DNA looks like the wave of the future.

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