All About Olaparib

Olaparib is a chemotherapy drug indicated for the treatment of different cancers in advanced stages. Its trademark is Lynparza and it was developed by the pharmaceutical company AstraZeneca.

There are different pharmaceutical forms of olaparib, and one or the other is indicated depending on the pathology and the stage of the patient. For example, the tablet formulation is used as monotherapy for the maintenance treatment of adult patients with high-grade epithelial ovarian and fallopian tube cancer. It also works for relapses in patients on platinum-based therapy.

On the other hand, olarparib capsules are used to treat cancers that have a mutated gene: BRCA. This gene plays a very important role in the development of cancer, especially breast and ovarian.

Olaparib capsules and tablets are not interchangeable due to differences in dosage and bioavailability of each formulation. On the other hand, it should be mentioned that the adverse effects that these formulations can cause in patients who take them are:

• Sickness
• Diarrhea
• Fatigue
• Neutropenia
• Thrombocytopenia
• Dizziness

Mechanism of action of olaparib

Olaparib is a drug that inhibits some human enzymes responsible for correct DNA repair. These enzymes are known under the name of PARP.

It has been shown in vitro to inhibit the growth of selected tumor cell lines and to inhibit the growth of tumors in vivo. It can be used both in monotherapy treatment and in combination with previously established chemotherapies.

When olaparib binds to these enzymes that are associated with DNA, through a series of reactions, it manages to prevent its repair. In healthy cells, this repair requires the BRCA-1 and BCRA-2 genes to function properly. In tumor cells that show a malfunction of these proteins, other alternative repair pathways that are prone to errors begin to be activated, causing greater genomic instability.

After several rounds of replication of these tumor cells, genomic instability can reach intolerable values. As a consequence, cancer cells die. The reason for this is that they have a high number of DNA damage compared to normal ones.

In studies carried out with patients who had a BRCA mutation, and therefore this protein did not function correctly, it has been seen that the administration of olaparib after treatment with platinum was beneficial. The result was a delay in tumor progression and an increase in overall survival versus platinum-only treatment.

Olaparib and BRCA

As we have mentioned, although it can be used to treat other cancers, olparib is indicated above all in the treatment of breast cancer. Mainly if it is advanced neoplasms. Also in metastatic ovarian cancer.

Regarding breast cancer, one of the most frequent molecular events in triple negative breast tumors is the alteration of the function of the BRCA protein. This oncological variety is one of the most aggressive for women,

Among women with breast cancer with a BRCA1 gene mutation, more than 80% have triple negative breast cancer. About 15% of patients with ovarian cancer and 5% of patients with breast, pancreas, or prostate cancer have inherited BRCA1 or BRCA2 mutations.

Olaparib is an inhibitor of PARP which, as we have seen, are proteins that help repair damaged DNA. Because BRCA mutations can also hinder DNA repair, similar inhibition of this process with olaparib can cause cancer cell death.

Different phase II clinical trials have evaluated the efficacy of olaparib as monotherapy and in combination with other chemotherapeutic drugs. The efficacy of olaparib, as monotherapy, in highly pre-treated patients with advanced breast cancer, had a higher objective response rate.

Conclution

Olaparib, by inhibiting PARP, represents a novel approach as an antineoplastic treatment. In this way, you can solve an unmet need in BRCA-associated cancer patients.

When dealing with advanced neoplastic pathologies, the treatments are not easy. The combination of therapies and long-term follow-up of the patient is always required. The ideal is to be advised by an oncological group that is always attentive to the needs of the patient and considers all the variables.