 In our environment, our cells are subject to all kinds of stresses that cause breaks in our DNA, from stress to aging and UV from the sun. Luckily, our cells have mechanisms in place to perfectly repair broken DNA. Cancer cells, however, take advantage of these DNA repair processes. In fact, some cancer cells often prefer to not perfectly repair DNA breaks and instead introduce errors. So why would cancer cells want to have improperly repaired DNA? Well, when DNA is improperly repaired, errors are introduced in the DNA sequence, and this provides the opportunity for mutations to occur, or changes in the DNA sequence. Mutations in cancer cells can create more malignant or aggressive cancer cells. We call this type of DNA repair error-prone repair. However, DNA damage is a double-edged sword, and too much DNA damage can also kill cancer cells. So what if we could figure out if a cancerous tumor is using the reliable DNA repair pathway, or the error-prone one? Then we could predict if a patient's tumor is more likely to become more aggressive, and perhaps we could target treatments accordingly. And that's exactly what the scientists in the laboratory of Dr. Philip Connell at the University of Chicago did in their paper titled, DNA Repair Pathway Gene Expression Score correlates with repair proficiency and tumor sensitivity to chemotherapy, published in Science Translational Medicine in March 2014. In this paper, scientists looked at established data from the Cancer Genome Atlas containing hundreds of different cancer samples and clinical data, and they defined a set of four genes or chunks of DNA that make protein involved in DNA repair. The activity of these four genes determines how much protein is produced. When lots of protein is produced from these four genes, the sample is set to have a high RPS score, or recombination proficiency score. When little protein is produced, it has a low RPS score. Interestingly, the scientists found that in hundreds of different cancer cells, a low RPS score meant that the cells were using error-prone DNA repair, and were accumulating lots of mutations. Whereas a high RPS score meant that the cells were using a faithful DNA repair mechanism that doesn't introduce errors, and were accumulating fewer mutations. So that's great. Now we have a tool to differentiate patients that have tumors that repair DNA reliably from patients with tumors that repair DNA while introducing errors. But what does this mean for prognosis and treatment? Well, the scientists went on to show that breast and lung cancer tumors that had a low RPS score behaved more aggressively, and had more invasion of the lymph node, and potential for metastasis. These low RPS tumors repair DNA using the error-prone method. The scientists took this a step further and wanted to find a way to treat these tumors with a low RPS score that introduced errors when they repair DNA. They found that specific types of chemotherapy that are based on platinum can very efficiently kill cancer cells that have a low RPS score, and that repair DNA using the error-prone method. However, these platinum-based chemotherapies don't actually kill cancer cells with high RPS scores. So what can we take away from this? The scientists have defined a set of four genes that alone define the RPS score. This RPS score can predict tumor aggressiveness. A low RPS score corresponds to a more aggressive tumor, and this is because the tumor is repairing DNA using the error-prone method. Interestingly, the RPS score can also predict which patients are more likely to respond to a specific category of chemotherapy. So what does this mean for you? This is a very significant advancement in our understanding of what happens inside cancer cells during cancer progression, and is taking us one step closer to developing more targeted treatments for patients based on the activity of genes inside tumor cells. In this case, perhaps we should only be treating tumors with a low RPS score with platinum-based chemotherapy for breast and lung cancer. Of course, before we use the RPS score for clinical purposes, we need to undertake thorough clinical trials to confirm this. For now, this important finding shows us that looking at how cancer cells repair DNA can make a big difference for treatment and clinical outcome for cancer patients. This video has been produced by Eureka Science. Stay in touch with Eureka Science, like us on Facebook, follow us on Twitter, or visit us at EurekaScience.org. Thank you for watching!