(Philadelphia, PA) – Proteins commonly known as BRCA – short for BReast CAncer susceptibility gene- serve a critical role in cellular DNA repair, but when mutated they allow genetic errors to replicate, facilitating cancer development. If the BRCA repair system is disabled in cancer cells, the cells simply turn to backup repair mechanisms and adapt to alternative repair pathways, a survival mode that also underlies their ability to evade targeted drug therapies.
Now, new research by scientists at the Lewis Katz School of Medicine at Temple University (LKSOM) shows that it is possible to eliminate at least two backup repair mechanisms at the same time using two targeted therapies. The strategy effectively narrows down the number of secondary repair pathways available, helping to ensure cancer cell eradication.
The novel approach, described June 12 in a paper published in Cell Reports, is named dual synthetic lethality, so-called because cancer cell death is induced by two drugs targeting distinct DNA repair pathways at the same time. “Cancers cells have multiple ways of protecting themselves from death,” explained senior investigator Tomasz Skorski, MD, PhD, Professor of Microbiology and Immunology and Associate Professor at the Fels Institute for Cancer Research and Molecular Biology at LKSOM.
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