PARP Inhibitors: Potential GameChangers For Pancreatic Cancer??

Seems like cancers are running a marathon within themselves too…Latest data reveals, Pancreatic cancer spearheads breast cancer as the third leading cause of cancer death in US..!

It is heartbreaking, but even today Pancreatic cancer sits at the backseat in terms of overcoming the common problems that hinder the treatment of pancreatic cancer. Lack of early symptoms, high resistant towards chemotherapy and fatality of the disease are still amongst the common issues. Fortunately, with science progressing with technologies and innovative testing methods, PARP Inhibitors a common class of drugs being clinically tested for the several cancers including pancreatic seem to be the immediate “ray of hope”.

What are PARP Inhibitors and DNA Repair Genes/ Proteins?

Poly(ADP-ribose) polymerase (PARP), as the name suggests is the enzyme present in the human body that is known to repair any sort of damage that may occur in the human DNA. During the course of cell cycle, several times the DNA undergoes damage and is simultaneously repaired. This process remains the same in cancer cells as well.

Proteins such as BRCA1/2 and PALB1 play a significant role in repairing the double strand damage in the DNA. However, if the gene for one of these proteins undergo mutation, the repair is halted and DNA becomes erroneous. This faulty DNA can then become a potential reason for cell death.

This science, knocked researchers’ heads and PARP became a potential target for cancer therapy. Therefore, they formulated inhibitors for these enzymes that could potentially help to stop cancer cells from repairing and growing.

Clinically, where are PARP Inhibitors and Pancreatic Cancer Together?

Latest data presented at ASCO 2019 clearly outlines the encouraging results of the PARP inhibitors used for patients with pancreatic cancer. The trial enrolled patients with BRCA1, BRCA2 or PALB2 mutations which is responsible for defective DNA repair and can be hereditary in nature. The trial also includes patients with non hereditary form of the mutations.

Findings from the study suggest that patients treated with PARP inhibitors lived a median of 9 months and did not show cancer progression (also called progression free survival). Fortunately, about 90% of the patients experienced disease control after the medication.

What Is Latest With PARP Inhibitors?

Considering the market and clinical success of the PARP Inhibitors in the ongoing trials for pancreatic cancer, one of the important additions to the NCCN guidelines include,

-Germline testing should be considered for all pancreatic cancer patients

-Molecular analysis of the tumor must be considered for patients with metastatic disease

This indeed was supported with data. Memorial Sloan Kettering Cancer Centre offered germline testing to families for about 76-88 cancer genes alongside genetic counselling. A total of about 10,000 people received the tumor DNA sequencing and 1040 were furthered for germline analysis. Of these, 176 (16.9%) showcased genes associated with pancreatic cancer which clearly indicates that only 42% of these would have been detected upon following the existing clinical guidance. Germline testing clearly could be indicative of whether a patient could be a potential patient for PARP Inhibitor treatment.