CRISPR Genetic Technology Reveals the Cause of Resistance to PARP Inhibitors

In cancer, synthetic lethality is the strategy behind PARP inhibitors, a new generation of ovarian and breast cancer medicines. However, these medicines do not work in some patients. Recent cancer research has focused on why resistance develops to these drugs. In May 2018, Nature Communicationspublished a study in which the mutations causing PARP drug resistance were discovered using CRISPR.

PAPR1 proteins participate in healthy cells’ DNA repair. Their activity is particularly high in cancer cells. PARP proteins help cancer cells survive, especially if the patient has mutations in other DNA repair genes.

PARP inhibitors block these proteins, causing cancer cells to die. They are particularly effective in patients with BRCA gene mutations. This is an example of synthetic lethality (death) in cancer. When BRCA genes are nonfunctional, cancer cells try to repair their DNA using PARP proteins. Blocking PARP allows damage to accumulate and eliminates these cells. In clinical use, the first PARP inhibitor approved by the FDA was olaparib, marketed as Lynparza. Olaparib is used to treat certain types of breast and ovarian cancer.

According to the Research Findings:

Researchers at the Institute of Cancer Research in London used crispr/cas9 gene editing to create different mutations in the PARP1 gene. They aimed to identify the mutation responsible for drug resistance in PARP1. They examined how CRISPR-created mutations affected cancer cells’ responses to PARP inhibitors. As a result, they discovered PARP gene mutations that confer resistance to PARP inhibitors.

What Does This Study Tell Us?

• CRISPR genetic engineering technology identified mutations in the PARP gene that cause drug resistance.
• Identifying such mutations allows personalized ovarian and breast cancer treatment and may help plan the optimal duration of olaparib treatment.
• It must be emphasized that these mutations were discovered by creating them through genome editing in the laboratory. Studies in actual patient cells are needed to confirm them.
• This study is important for its contribution to precision medicine in clinical practice.
• Beyond offering effective cancer treatments, CRISPR technology holds great promise for identifying the mutations that are the fundamental cause of cancer.
• All crispr/cas9 Gene Editing Technology News