Scientists have made a major discovery about how cells repair broken strands of DNA that could have huge implications for the treatment of cancer.

Their study, published in Nature today, uncovered a brand new protein complex in cells that shields broken DNA ends and controls the way in which it is repaired.

The new complex pushes cancer cells to use a particular type of DNA repair system that is vulnerable to targeting by exciting new drugs called PARP inhibitors or platinum-based chemotherapies.

The landmark study was a result of collaboration between the University of Toronto, The Institute of Cancer Research, London, The Netherlands Cancer Institute, and the University of Bern.

The discovery could lead to tests to direct and monitor treatment for patients with mutations in BRCA1, BRCA2, or other DNA repair genes, treated with platinum-based chemotherapies or PARP inhibitors.

The newly named ‘Shieldin’ complex was also found to be important for generating the right type of antibodies during an immune response, and mutations could lead to immune-related disorders.

The study was funded by a variety of organizations worldwide, including Canadian Cancer Society and the Canadian Institutes of Health Research, and Cancer Research UK and Breast Cancer Now in the UK.

Taking advantage of cancers' weakness

PARP inhibitors are hugely promising treatments because they take advantage of a major vulnerability of some cancers—a weakness in the ability of cancer cells to repair their DNA. Traditional platinum-based chemotherapies are also being used in a more targeted way to take advantage of DNA repair weaknesses.

When intact, the newly discovered Shieldin complex was found to contribute to this vulnerability by attaching to the broken DNA, forcing cancer cells to attempt to repair their DNA in a way that makes them susceptible to PARP inhibitors and platinum chemotherapies.

But when mutations are introduced in the components of the complex, the researchers found that cancer cells grown in the lab and in mice used an alternative way to repair DNA and quickly became resistant to PARP inhibitors.

The PARP inhibitor drug olaparib is approved in the US and Europe for treating ovarian and breast cancers with BRCA mutations and looks promising against some prostate cancers—so the results could have a wide impact on cancer treatment if mutations in the ‘Shieldin’ complex are shown to lead to treatment failure in the clinic.