Lynparza (olaparib) works by trapping a DNA repair enzyme called PARP onto damaged DNA, preventing cancer cells from fixing broken strands. In cells that already have faulty DNA repair genes, like BRCA1 or BRCA2, this creates a buildup of irreparable damage that kills the cell. It’s a targeted cancer therapy taken as a pill, approved for certain types of ovarian, breast, pancreatic, and prostate cancers.
How PARP Inhibition Damages Cancer Cells
Your cells constantly accumulate small breaks in their DNA from normal metabolism, toxins, and other stressors. A family of enzymes called PARP acts as a first responder to these single-strand breaks, latching onto the damage site and coordinating repairs. Lynparza blocks PARP from completing this job, but it does something more damaging than simply switching the enzyme off: it traps the inactivated PARP protein directly onto the broken DNA strand.
That trapped PARP-DNA complex becomes a physical roadblock. When the cell tries to copy its DNA during division, the replication machinery slams into the trapped complex. The replication fork stalls and then collapses, converting what started as a minor single-strand break into a far more serious double-strand break. Double-strand breaks are one of the most dangerous forms of DNA damage a cell can experience.
Why It Selectively Kills Cancer Cells
Healthy cells can handle double-strand breaks because they have a backup repair system called homologous recombination, which is controlled by the BRCA1 and BRCA2 genes. When PARP is knocked out, normal cells simply rely on this backup pathway to fix the damage and survive.
Cancer cells with BRCA mutations don’t have that option. Their homologous recombination pathway is broken or severely impaired. So when Lynparza generates double-strand breaks by trapping PARP, these cells have no reliable way to repair them. The accumulating damage either triggers programmed cell death or forces the cell to use error-prone repair methods like non-homologous end joining, which introduces so many DNA rearrangements that the cell can no longer function. This concept, where disabling two repair pathways simultaneously is lethal but losing either one alone is survivable, is called synthetic lethality. It’s why Lynparza can destroy tumor cells while largely sparing healthy tissue.
Which Cancers Lynparza Treats
The FDA has approved Lynparza for several cancer types, all tied to specific genetic markers that predict the drug will work. The common thread is that the tumor must have some form of DNA repair deficiency.
- Ovarian cancer: Approved as maintenance therapy after platinum-based chemotherapy in patients with BRCA-mutated advanced disease, both as a first-line treatment and for recurrent cancer. It can also be used alongside bevacizumab for tumors that test positive for broader homologous recombination deficiency (HRD), even without a specific BRCA mutation.
- Breast cancer: Approved for patients with inherited BRCA mutations whose tumors are HER2-negative. This includes both early-stage high-risk breast cancer (after chemotherapy) and metastatic disease.
- Pancreatic cancer: Approved as maintenance therapy for metastatic pancreatic cancer with inherited BRCA mutations, after at least 16 weeks of platinum-based chemotherapy without progression.
- Prostate cancer: Approved for metastatic castration-resistant prostate cancer with mutations in homologous recombination repair genes, after prior hormone-blocking treatment has stopped working.
Genetic testing of the tumor (and sometimes a blood test for inherited mutations) is required before starting treatment. Without confirmed DNA repair deficiency, the drug is unlikely to provide meaningful benefit.
What Treatment Looks Like
Lynparza is an oral medication, not an infusion. The standard dose is two 150 mg tablets taken twice daily, about 12 hours apart, for a total of 600 mg per day. It can be taken with or without food. Tablets also come in a 100 mg strength for dose adjustments.
For maintenance therapy in ovarian cancer, the typical treatment plan is up to two years or until the cancer progresses, whichever comes first. Duration varies for other cancer types depending on the clinical situation. In the landmark SOLO-1 trial of first-line ovarian cancer maintenance, patients on Lynparza had significantly longer survival compared to placebo, with median overall survival in the placebo group at about 75 months while the Lynparza group hadn’t yet reached their median, representing a 45% reduction in the risk of death.
Common Side Effects
Nausea is the most frequently reported side effect, affecting more than 75% of patients taking any PARP inhibitor including Lynparza. It tends to be most noticeable in the first few weeks and is often manageable with anti-nausea medication. Vomiting occurs less frequently but follows the same pattern.
Fatigue is nearly as common, reported in 60% to 70% of patients, though most experience it at mild to moderate levels. It can be persistent and is one of the side effects that most affects daily life during treatment.
The most clinically significant side effect is anemia, the most common blood-related toxicity. In the SOLO-1 ovarian cancer trial, 22% of patients on Lynparza developed severe anemia requiring intervention, such as dose reduction or blood transfusion. Severe drops in infection-fighting white blood cells (neutropenia) occurred in about 9% of patients on Lynparza in that same trial. Regular blood count monitoring throughout treatment is standard practice to catch these changes early.
How Cancer Cells Develop Resistance
Some tumors eventually find ways to survive despite PARP inhibition. The most well-understood mechanism is a reversion mutation: the cancer cell essentially repairs its own BRCA gene, restoring homologous recombination and giving it back the ability to fix the double-strand breaks that Lynparza creates. These secondary mutations emerge under the selective pressure of the drug, with resistant cell populations gradually taking over.
Other resistance pathways include changes that prevent PARP from being trapped on DNA in the first place, or alterations to proteins that protect stalled replication forks from collapsing. Notably, many of these resistance mechanisms also confer resistance to platinum-based chemotherapy, since both drug classes exploit the same DNA repair vulnerabilities. This overlap is one reason why the sequence and timing of treatments matters in long-term cancer management.