Metabolic and translation regulation of DNA repair in metastatic cancer and lymphomas

DNA repair requires the timidly expression of DNA repair proteins and metabolites required for the process of synthesizing new DNA. Cancer cells and in particular metastatic tumors are continually exposed to increased genomic instability making them particularly reliant on these features. We found that pharmacologically interfering with the production of DNA repair proteins or metabolites, induces catastrophic events that result in cancer cell death or decreasing capacity to repair DNA damage in cancer cells that survive the intervention. Sub-lethally damage cancer cells are extremely sensitive to additional DNA damage induced by exogenous DNA damaging agents such as ionizing radiation and/or chemotherapy, resulting in the preferential radio- and chemosensitization of cancer cells. We applied these concepts to increase the response to standard treatment in patients with brain metastases from solid tumors like breast cancer and lung cancer, and to lymphomas.