PARP Inhibitor implications and analysis: What is a PARP inhibitor? What are PARP inhibitor implications and analysis? PARP ( Poly ADP-Ribose Polymerase) Inhibitor is hypothesized that it may prove highly effective therapies for cancers with BRCAness, due to the high sensitivity of the tumors to the inhibitor and the lack of deleterious effects on the remaining healthy cells with functioning BRCA HR pathway. This is in contrast to conventional chemotherapies which are highly toxic to all cells and can induce DNA damage in healthy cells, leading to secondary cancer generation.
PARP Inhibitor implications
PARP inhibitors affect cancer cells by altering their ability to replicate DNA and grow. In theory and in animal models, they work synergistically with more traditional chemotherapy agents, since PARP inhibition should make chemotherapy (or any drug which damages DNA) more effective. This study was presented at an ASCO plenary session and the reported results are exciting, both for breast cancer and other cancers where these drugs have just begun to be studied.
Dr. J. Dirk Iglehart of the department of surgery at Brigham and Women’s Hospital and the department of cancer biology at the Dana-Farber Cancer Institute in Boston, and co-author of an accompanying journal editorial said:
“When you disable PARP, you prevent the cell from repairing itself, and cancer cells that are deficient in BRCA are much more sensitive to this effect. When you inhibit PARP, they can’t stand it.”
Dr. Iglehart thinks that combining a PARP inhibitor with chemotherapy drugs that damage DNA might make the drug even more effective.
“You might then push cancers over the cliff that would be only susceptible to a PARP inhibitor. PARP inhibitors may be used for tumors that Herceptin or tamoxifen are totally incapable of treating. That’s true for ovarian cancer, too. There is nothing to treat that disease.”
Two other trials of PARP inhibitors, which were reported on during the American Society of Clinical Oncology annual meeting in June, also found that they were effective in treating breast cancer.
PARP Inhibitor Analysis
For the last few years, PARP inhibitors have been discussed as having great potential in combination with standard chemotherapy drugs to treat cancer. This paper, a randomized Phase II study treating triple negative breast cancer patients with metastatic disease, showed that patients who received the PARP inhibitor along with standard chemotherapy showed statistically significant improvements in response rate, progression free survival, and overall survival. While this was a small study in only 123 patients, the magnitude of the postive results have prompted the initiation of a Phase III (registration-intent) trial.
This is also important because PARP inhibitors are also being tested in other cancers. For example, Abbott Labs’ PARP inhibitor, ABT-888, is currently being tested in trials in melanoma, acute leukemia and myelodysplasia, lymphoma, as well as some other, earlier stage, trials.
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