Researchers at the Szeged Biological Research Centre (SZBK), led by Gyula Timinszky, are working on enhancing the effectiveness of a currently used drug therapy to treat more types of cancer, according to an announcement on the institution’s website, part of the Hungarian Research Network (HUN-REN).
One in three Hungarians will develop a malignant tumor during their lifetime, and although recovery rates have improved in recent years, cancer remains the second leading cause of death in Hungary. Cancer treatment strategies are becoming more refined and targeted as the molecular workings of tumor cells are better understood.
The new therapies exploit a phenomenon known as synthetic lethality: cells can tolerate deficiencies in certain molecular pathways individually but die when two critical pathways fail simultaneously. This concept was first proposed nearly two decades ago concerning BRCA1 and BRCA2 mutations, which predispose individuals to breast, ovarian, and prostate cancers by impairing specific DNA repair pathways. By inhibiting another pathway involving the PARP enzyme, these cancer cells can be effectively killed.
Gyula Timinszky’s team at the HUN-REN SZBK Genetic Institute has identified new targets that make additional cancer cell types susceptible to PARP inhibitors. Their recent study, published in the prestigious journal Nucleic Acids Research, demonstrated that reducing or eliminating POLE3 and POLE4 proteins in cancer cells causes them to stop dividing and die even at low doses of PARP inhibitors. This new example of synthetic lethality differs from the classical BRCA1/2 pathway and can be applied to cancers without BRCA mutations or those that have restored their DNA repair pathways through new mutations.
Based on these findings, the research team is now developing a strategy to inhibit the POLE4 protein in any cancer cell, potentially extending the benefits of PARP inhibitor therapy to cancer types resistant to traditional treatments.
(MTI)
Photo: Yvette Frank
