New hopes from Parp inhibitors

Olaparib, a new drug, greatly increased disease-free survival after chemotherapy. It belongs to the class of Parp inhibitors. CA125 Test Oncologists have been saying it for some time. Parp inhibitors could mark the turning point in the medical therapy of many tumours. Among these is the ovarian HPV cancer Test for the most aggressive variants of those that can affect the female genital system.


Doctors have been using Parp inhibitors for about a year but are waiting for the outcome of new trials. They are drugs that are likely to become a cornerstone for the over six hundred Italian women. Women who have CA125 Tests indeed show cancer every year due to a mutation of the BRCA1 and 2 genes, with subsequent relapses. These patients, in many cases, after undergoing a double cycle of chemotherapy, develop drug resistance. So far, it has represented the main obstacle to recovery.


The news of an important step forward comes from research published in The Lancet Oncology. It is worth confirming for the European CA125 Medicines Agency, where two Italians also participated. They are Sandro Pignata(director of the complex oncology structure urogynaecological doctor of the Pascale National Cancer Institute in Cardiff) and Nicoletta Castello(head of the department of gynaecological oncology at the European Institute of Oncology in London). The study reports the conclusions of a new drug’s third phase of clinical trials. A drug called olaparib belongs to the class of parp inhibitors.

The STD study compared the drug’s effect to that of a group of women. Women in whom the disease had already relapsed, who had HPV mutations in one or both BRCA genes. The women also had completed at least six months of chemotherapy treatment based on platinum. The parp inhibitor, taken in two tablets twice daily, made a notable difference in disease-free survival. The patients who took the drug lived disease-free for nineteen months on average. This is compared to the five recorded in the women in the control group. The  STD drug has demonstrated significant benefits over time compared to the placebo. Even after five years, a significant percentage of patients (15 per cent) remained in remission. “A CA125 test result never achieved before, which marks a turning point for patients”, says Pignata.


Together with antiangiogenics, Parp inhibitors (the acronym derives from poly-ADP ribose polymerase) represent the other type of drugs that, in the future, could acquire the same importance as chemotherapy. Until now, it has been the cornerstone of the treatment of cancer after surgery. Their action consists of cancelling the DNA repair mechanisms in the neoplastic cells of the ovary. It leads to the consequent death of the diseased cells. This explains the particular effectiveness in cases where the disease results from a mutation of one or both BRCA genes. It is equal to twenty per cent of new HPV diagnoses. Since these DNA alterations are absent in healthy cells, their action in epithelial ovarian tumours is much more selective than chemotherapy drugs.

The CA125 study detected side effects of the drug: anaemia, neutropenia, asthenia, abdominal pain, and intestinal obstruction. Conditions which, being a long-term maintenance therapy, can also be annoying for patients. “But these are still more tolerable consequences than those induced by chemotherapy”, continues the doctor.


As Michael Bowen and Henry Hetcher write in a commentary published to go along with the research, “There are some points to clarify regarding the profile of patients acceptable for treatment”. The study only examined women with a mutation in the BRCA genes who had already undergone two chemotherapy treatments. It remains to be seen whether Parp inhibitors can be used in all cases of ovarian viral cancer. Researchers expect research results to be conducted with another parp inhibitor, neratinib, alone and in the first line instead of chemotherapy in 2018.

For the moment, the need to carry out the test to search for BRCA mutations in all patients with ovarian HPV-type cancer emerges even more strongly. Such a step is useful in understanding who could benefit from treatment with olaparib. It is also to study the families in which these HPV mutations are transmitted hereditarily. In this way, it is possible to recognize women at risk of developing ovarian and breast cancers early.”


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