Preliminary research presented today during the annual meeting of the Society of Gynecologic Oncology on Women’s Cancer bodes well for advances in understanding and treatment of ovarian cancer. The research shows that the Poly(ADP-ribose) polymerases 7 or PARP-7 protein may play a significant role in survival for ovarian cancer patients.
Ovarian cancer patients with genetic amplification in the PARP-7 protein survived longer than those without the mutation according to a presentation today at the Society of Gynecologic Oncology’s 2018 Annual Meeting on Women’s Cancer. These results call for researchers to further investigate the PARP-7 protein.
… patients with a gene amplification to PARP-7 had a median overall survival greater than 6 months compared to patients that did not have any gene amplification of PARP-7…
Lead researcher Lavanya Palavalli Parsons, MD, of the University of Texas Southwestern Medical Center in Dallas, Texas, presented research delving into the PARP-7 protein in ovarian cancer and genetic alterations in patients.
Some members of the PARP family of proteins, such as PARPS 1 and 2 help repair DNA damage in cancer cells, allowing cells to survive. When these PARPs are blocked with PARP inhibitors, DNA repair is stopped causing cell death, and killing the cancer cells. PARP inhibitors are one of the most recent advancements in ovarian cancer. In contrast, the specific molecular and cellular functions of PARP-7 have not yet been determined, but these promising studies suggest that further investigation is warranted.
In the project, she specifically looked for patients with ovarian cancer that have gene amplification to PARP-7 compared to the patients who did not have genetic amplification to PARP-7. Her investigation showed that patients with a gene amplification to PARP-7 had a median overall survival greater than 6 months compared to patients that did not have any gene amplification of PARP-7. These results show a significant difference in survival.
“If you took the specific patients who had alterations, they all had gene amplifications which correlated with higher levels of expression of PARP-7,” Palavalli Parsons said.
“These patients with ovarian cancer lived longer.”
“The PARP family consists of 17 members with most of the current research focused on the nuclear PARPs, PARP 1-3. Minimal research has been conducted on the other PARPs, though previous literature has suggested a significant role for PARP-7 in cancers,”she said.
Research has shown PARPs have widespread functions that are vital for cellular homeostasis. While the majority of the PARP-mediated functions are related to cellular stress response, results from recent investigations imply non-stress functions as well.
In her study, she used the Cancer Genome Atlas database (TCGA), which is a catalog of the genetics of each patient’s cancer samples. The catalog uses genetic sequencing.
“The PARP family is still a mystery and that is why we need to continue to research PARPs,” she said. “I feel like we are only seeing the tip of a huge iceberg which is on the verge of being uncovered with the influx of new knowledge about the PARP family.”
A phase I trial of Vigil® immunotherapy (bi-shRNAfurin and GMCSF Augmented Autologous Tumor Cell Immunotherapy) shows excellent tolerability with limited side effects for ovarian cancer patients. During a clinical trial, 29 patients with recurrent ovarian cancer received Vigil vaccine immunotherapy. Vigil is a genetically engineered vaccine made from tumor cells acquired from each specific patient. [see note] The vaccine, produced by Gradalis, enhances the targeting of cancer cells.
Lead Researcher Rodney Rocconi, MD, of University of South Alabama-Mitchell Cancer Institute in Mobile, Ala., said the new technology is the quintessential definition of targeted therapy because it is patient-derived.
Before patients were considered for the trial, an Enzyme-Linked ImmunoSpot or ELISPOT test was used to see if patient’s T cells, immune cells, would be activated. Patients with T cell activation had a significant increase in survival. Overall, 20 of 29 patients hit the three-year mark of survival with the median not being reached yet in the three-year study. Patients only reported a negative side effect of fatigue.
This vaccine combines the extra targeted specific therapy with traditional novel immunotherapy, he said.
“As we dig further and further into the causation of cancer, we should probably open the thought of being as specific as possible to individual cancer cells in what we need to target for therapy,” Rocconi said.
“This type of therapy is unique because it is targeting the patient’s specific cancer cells. You cannot get more targeted than this,” he added.
[note] The investigational drug Vigil, being developed by Gradalis, is composed of autologous tumor cells harvested from the patient at the time of initial de-bulking surgery which are then transfected extracorporeally, with a plasmid encoding for the gene for GM-CSF, an immune-stimulatory cytokine, and a bifunctional, short hairpin RNA which specifically knocks down the expression of furin, the critical convertase responsible for production of the two TGβ isoforms (TGFβ-1 and TGFβ-2).
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