New Weapon Against PARP Inhibitor-Resistant Ovarian Cancers

On December 22, 2023, a new editorial piece titled “One more step toward treatment of PARP inhibitor-resistant ovarian cancers” was published in Oncotarget Volume 14 with the title “One more step toward treatment of PARP inhibitor-resistant ovarian cancers.”

Over 80% of ovarian cancer cases return, resulting in around 12,000 deaths per year in the United States. While targeted therapies such as poly (ADPribose) polymerase inhibitors (PARPis) have been approved by the FDA for both initial and recurrent treatments, extending median progression-free survival for people with homologous recombination repair (HRR) deficiency, the emergence of PARPi resistance remains a common issue among patients. As a result, overcoming resistance to PARPi treatment in ovarian cancer has become a serious therapeutic issue, necessitating novel approaches.

In this editorial, Mayo Clinic School of Medicine and Science researchers Upasana Ray, Prabhu Thirusangu, and Viji Shridhar reacted to this unmet need with their present study, which revealed promising findings relating to the Pixatimod (PG545) medication, a sulfated small molecule compound. This chemical, designed with a core structure similar to heparan sulfate, targets heparanase and heparin binding growth factor (HB-GF) signaling.

“Our present study has revealed a previously unknown effect of PG545 in ovarian cancer cells, inducing DNA damage. The investigation unveiled that PG545 induces both single- and double-strand breaks in DNA while also promoting the autophagic degradation of RAD51, a critical DNA repair protein, thereby impeding the homologous recombination repair (HRR) pathway in cancer cells.”