Meet the Next Game Changer: Drugs Attacking Faulty DNA Repaired Mechanism Wow International Experts at ESMO 2019

The European Society for Medical Oncology’s annual meeting is one of the greatest gatherings of oncological experts anywhere in the world. Every year, researchers and physicians come together to share their findings and experiences in providing treatment for cancer patients. For ESMO 2019, the presentation of the PARP inhibitor stole the show, with research findings that stunned the audience like a one-two combination punch.
 
As we know, cancer cells start off as normal cells until mutations occur in the genes, resulting in uncontrolled replication and proliferation of the mutated cells. Normally, the natural healing mechanisms of the body will rectify these anomalies and return them to normal function. If a cell has mutated beyond repair, its own self-destruct mechanism will be activated leading to the death of the cell.

The DNA repair process requires a tumor suppressor gene such as BRCA and an enzyme called Poly (ADP-ribose) polymerase (PARP) to work in tandem. In some case only the BRCA gene malfunctions, while only the PARP enzyme continues to soldier on. Thus, the repair is not hundred percent complete, leaving a partially repaired/damaged cell.
 
As mentioned earlier, human cell has a self-destruct mechanism embedded, ready to be used if it is damaged beyond repair. However, the cells partially repaired by PARP are not considered damaged enough to trigger this particular mechanism. These malfunctioning cells thus continue to proliferate and multiply, finally becoming what we call “cancer”.
 
The PARP inhibitors have been developed to break through that impasse: by blocking the PARP enzyme from continuing to attempt cell repair when the BRCA gene failed to do complete its duty, the damage of the cell will stay at the level where its own self-destruct sequence can be triggered. To put it simple, PARP inhibitors “shut down” the faulty repair process and let the damaged cells die as they are supposed to be.
 
Furthermore, since PARP inhibitors only affect the cells with this kind of faulty repair mechanism, the healthy cells of the patient are unscathed by this treatment, which qualifies the drugs as a form of targeted therapy. There is currently a variety of PARP inhibitor medications—olaparib, niraparib, rucaparib, and talazoparib—that have received US FDA approval for a variety of cancers.  
 
But the thing that turned PARP inhibitors into the star of the show at ESMO 2019 is the fact that it has significant benefit even in non BRCA-associated cancers, such as ovarian. These results signal potential usefulness in the treatment of other forms of cancer.
 
In one study, time without progression in ovarian cancer patients have been significantly prolonged from an average of 16.6 months to 22.6 months. This is achieved by administering olaparib in tandem with bevacizumab (a cancer drug that works by preventing new blood vessels from being formed to feed the cancer cells) as a maintenance therapy after chemotherapy.
 
Other PARP inhibitors have also met with notable success. Administering niraparib after the completion of chemotherapy for metastatic ovarian cancer patients can prolong their time without progression significantly. Whereas combining veliparib with chemotherapy from the very beginning, and continuing with veliparib thereafter, also achieved very favorable results in ovarian cancer patients. These research findings are important milestones for patients with ovarian cancer, which is the fifth most common form of cancer among women.
 
The drugs’ efficacy against BRCA mutated cancers are still going strong as well.  Research on olaparib has been successful in saving lives by arresting the spread of castration-resistant prostate cancer (CRPC) during metastasis in men with BRCA mutated cancers. Veliparib, when combined with carboplatin and paclitaxel, also works well in HER2-negative advanced/metastatic germline BRCA-associated with breast cancer.
 
This medical breakthrough amounts to nothing less than a game changer in the fight against cancer. The known parameters for treatment have been expanded, as has the time in which cancer patients can be with their families and loved ones in comfort and wellbeing.
 




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