Despite exciting developments of PARP inhibitors over the years, limited knowledge exists in the mechanism of PARP-7 and its potential effect in targeted therapy for patients with ovarian cancer.
While PARP inhibitors continue to change the treatment landscape for ovarian cancer, the PARP-7 protein may play a significant role in survival outcomes for women with ovarian cancer, according to study results presented at the Society of Gynecologic Oncology’s Annual Meeting on Women’s Cancer.
“There has been a lot of exciting developments in the gynecologic oncology world with the FDA approval of PARP inhibitor drugs,” Lavanya H. Palavalli Parsons, M.D., gynecologic oncology fellow at UT Southwestern Medical Center, said in an interview with CURE.
“These drugs are primarily inhibiting PARP-1, -2 and -3. However, PARPs are a large family consisting of 17 members and so we were curious to see what role did the other PARPs play​ in ovarian cancer.”
Some members of the PARP family of proteins help repair DNA damage in cancer cells, allowing cells to survive; however, when these PARPs are blocked with PARP inhibitors, DNA repair is stopped causing cell death, which kills the cancer cells.
Despite all of the recent advancements with PARP inhibitors, the specific molecular and cellular functions of PARP-7 have not yet been determined. Therefore, using the Cancer Genome Atlas database (TCGA) — which is a catalog of the genetics of each patient’s cancer samples – Palavalli analyzed PARP-7 in high-grade ovarian cancer.
She specifically looked for patients with ovarian cancer that have gene amplification to PARP-7 compared with patients who did not have genetic amplification to PARP-7. The analysis showed that those with gene amplification to PARP-7 had a median overall survival (OS) advantage of 6.5 months compared with patients who had no gene amplification of PARP-7.
Similarly, patients who were platinum-resistant experience superior OS among those who had PARP-7 alterations compared with those who did not (11.7 months vs. 3.3 months).
Ultimately, when PARP-7 demonstrated having genetic alterations and higher expression levels, patients with ovarian cancer experienced significantly improved OS. Palavalli noted that in identifying that PARP-7 modified extracellular matrix protein helped her to understand the potential biology of PARP-7 significance to ovarian cancer.
“This research contributes to the body of literature for cancer biology and further understanding the PARP family,” she added. “This shows that PARPs have other roles than just repairing DNA damage, which has been traditionally perceived. We were able to identify specific proteins that are modified by PARP-7, which potentially can be targeted by drugs for therapeutic benefit.”
As a result, similar investigations are ongoing. “Further characterization of PARP-7 is being done at this time, which can lead to potential targets for drug development,” Palavalli said