Research ArticleCancer

DNA Repair Pathway Gene Expression Score Correlates with Repair Proficiency and Tumor Sensitivity to Chemotherapy

Science Translational Medicine  26 Mar 2014:
Vol. 6, Issue 229, pp. 229ra42
DOI: 10.1126/scitranslmed.3008291

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Navigating Tumor Therapy with an RPS

For cancer patients, DNA damage is a double-edged sword. Mutations can contribute to carcinogenesis, but the cancer cell can’t survive with too much DNA damage. Indeed, many cancer therapies aim at increasing DNA damage, but selecting the correct therapies for individual patients can be hit-or-miss. Pitroda et al. proposed that mechanisms of double-strand DNA break repair could correlate with cancer prognosis and could guide choices in cancer therapy.

The authors devised a recombination proficiency score (RPS) based on the expression levels for four genes involved in DNA repair pathway preference. They then validated the RPS in patients with either breast or non–small cell lung cancer. Tumors with low RPS—suppressed homologous recombination (HR)—were associated with greater mutagenesis and decreased likelihood of patient survival. This prognosis could be counteracted with platinum-based adjuvant chemotherapy—patients with suppressed HR were more sensitive to this treatment. These data suggest that RPS can help determine treatment course for cancer patients.