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The DNA damage response as a cancer therapy selection tool

The DNA damage response as a cancer therapy selection tool

To treat cancer patients successfully and with minimal toxic side effects precision therapies are of utmost importance. Our research program address challenges that can be identified in taking personalized cancer treatments forward, specifically developing better patient selection methods. Rooted in our experience in analyzing mechanisms of the DNA damage response and in particular the homologous recombination DNA repair pathway, we expect to widen the applicability of the successful concept of the synthetic lethality due to PARP-1 inhibition in BRCA-deficient tumors.

 A Schematic diagram of a model for repair a DNA double-strand break by homologous recombination

  A schematic diagram of a model for repair a DNA double-strand break by homologous recombination

This research program will result in optimized functional ex vivo assays for homologous recombination deficiency on fresh breast cancer tumor material. We are working to adopt the assay to other tumor sites. Importantly, we aim to correlate the outcome of the ex vivo DNA damage response assays and tumor response to PARP-1 inhibitor and/or cisplatin treatment in breast cancer patients. Furthermore, our functional ex vivo DNA damage response assays can be used to uncover novel biomarkers for homologous recombination deficiency with the use of NGS methods and bioinformatics. As a result many more patients that would benefit from therapies that target homologous recombination deficiency can be selected. See also: The DNA damage response in tissues and tumors.

Relevant publications

Naipal et al., Functional ex vivo assay to select homologus recombination deficient breast tumors for PARP inhibitor treatment.  Clin. Cancer Res. 20, 4816-4826.

Naipal et al., Tumor slice culture system to assess drug response of primary breast cancer.  BMC Cancer 16, 78.