DNA Repair Gene Mutations Predict Rucaparib Response for Ovarian Cancer

Poly ADP ribose polymerase (PARP) inhibitors are targeted cancer therapies which block PARP, an enzyme. Normally, PARP plays a role in DNA repair. Thus, inhibiting PARP prevents cancer cells from repairing themselves after damage. But how can researchers tell which cancer patients will respond to PARP inhibitors and which will not? According to BioNews, new research suggests that exploring DNA repair gene mutations can predict not only which patients with ovarian cancer will respond to treatment with rucaparib, a type of PARP inhibitor, but how well they will respond to treatment. Check out the full study findings published in Nature Communications.


According to Clovis Oncology, rucaparib is:

an oral, small molecule inhibitor of poly (ADP-ribose) polymerase (PARP)1, 2 and 3 is being developed in multiple tumor types, including ovarian and prostate cancers, as monotherapy and in combination with other anti-cancer agents.

Within this study, researchers analyzed pre-treatment tumor biopsies. The biopsies were utilized in a Phase 2 clinical trial evaluating rucaparib. However, in this study, researchers wanted to understand if the tumors showed any potential predictive biomarkers. A biomarker is usually some sort of measurable sign (a “biological marker”) which highlights some sort of process in the body. For example, blood pressure can be just as much of a biomarker as specific genes. In this case, researchers used biopsies from 491 patients with ovarian cancer. While not necessarily treatment-naive, no patients previously received PARP inhibitors. Within the clinical trial, patients received 600mg rucaparib 2x daily.

When analyzing the biopsies, researchers determined:

  • BRCA1 mutations predicted a better response to PARP inhibitor treatment. However, this is not necessary a new finding. In the past, BRCA1 and BRCA2-associated cancers have been shown to respond to PARP inhibitor therapy.
  • Beyond BRCA mutations, both RAD51C and RAD51D mutations also predicted rucaparib responses. Both of these genes are DNA repair genes.
  • Patients whose cancer was resistant to platinum-based chemotherapy also showed resistance to rucaparib over time. Thus, researchers suggest that rucaparib should be considered a first- or second-line therapy to avoid this.

Ovarian Cancer

There are four stages of ovarian cancer, which forms in the female ovaries. In stage one, the cancer is only found in one or both ovaries. By stage two, the cancer spreads to the pelvis and by stage three, the cancer spreads to the abdomen. Finally, in the fourth stage, the cancer metastasizes, affecting the bowel and bladder lining, lymph nodes, lungs, liver, or other areas of the body. However, early identification and treatment could prevent the cancer from spreading.

Altogether, there are also four forms of ovarian cancer. In small cell carcinoma of the ovary (SCCO), the rarest form (accounting for just 0.1%) of diagnoses, the cancer starts as a highly malignant tumor. Stromal carcinoma tumors develop in the connective tissue that produces hormones, while germ cell carcinoma tumors begin in the cells which eventually form the eggs. Overall, epithelial tumors are the most common form of ovarian cancer. These tumors form in the epithelial cells, a thin layer of tissue covering the ovaries.

In early stages, some patients will not show symptoms. When symptoms do appear, they include:

  • Abdominal or pelvic pain
  • Bloating
  • Appetite loss
  • Pelvic pain
  • Breast tenderness
  • Changes in urinary urgency or frequency
  • Menstrual irregularities
  • Increased testosterone
  • Abnormal vaginal secretions
  • Nausea or indigestion
  • General malaise
  • Unintended weight loss
  • Abdominal swelling or distention
  • Uterine thickening
  • Abnormal uterine or vaginal bleeding

Learn more about ovarian cancer.

Jessica Lynn

Jessica Lynn

Jessica Lynn has an educational background in writing and marketing. She firmly believes in the power of writing in amplifying voices, and looks forward to doing so for the rare disease community.

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