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w 10 | Live from the Labs cnrs I international magazine Cancer Two recent studies pave the way for improving cancer therapies on several fronts. Better Cures Ahead by Clémentine Wallace By irradiating a  dimer  of heavymass atoms to produce lowenergy electrons, researchers have demonstrated a concept of chemical physics that could one day lead to a more targeted and less toxic approach in radiation therapy.1 Today, radiotherapy consists in irradiating a patient’s tumor with X-rays in a wide range of energies, to ensure all cancer DNA is destroyed. While the X-ray beam aims at the tumor, it also affects healthy cells on its way, leading to burdensome adverse events. “This is like using a hammer to smash the tumor,” says Florian Trinter, who participated in the study.2 An ideal treatment would consist in irradiating the tumor alone, avoiding collateral damage. With this objective in mind, researchers have experimentally tested the “resonant-auger-driven intermolecular coulombic decay” concept, stating that irradiation should lead to the release of electrons within the irradiated molecule. The scientists fine-tuned an X-ray beam to the energy level required to excite a dimer of carbon monoxide. Electron spectroscopy then showed that 75% of the dimers excited emitted low- energy electrons. Interestingly, “the resonant approach is about ten times more effective in terms of energy production than the usual broadband irradiation,” explains Trinter. Co-author Marc Simon3 confirms that this approach could be very promising for radiotherapy. “A specific level of energy is required to excite heavy-mass atoms like carbon monoxide—a level at which our body’s atoms are not likely to ionize,” he says. “So if heavy-mass atoms could be introduced at the site of the tumor, irradiating the body at this specific level of energy would only damage the tumor’s DNA and spare the surrounding tissues.” Introducing heavymass atoms inside the tumor will be the next challenge. In an entirely different field called “chronotherapy,” researchers have devised a mathematical model able to predict, at the individual level, the time of day when a given chemotherapy has optimal effects.4,5 Indeed, both the safety and efficacy of most anticancer drugs are influenced by the body’s circadian clock. Researchers have shown that the timing of best tolerability, fortunately, coincides with that of best efficacy. Yet this optimal timing can vary by up to 12 hours depending on the patient. A team of scientists, led by CNRS researcher Francis Lévi,6 decided to uncover the individual factors that may influence it. Working with male and female mice with different genetic backgrounds, the researchers studied variations in the toxicity of irinotecan, a drug used to treat colon cancer. The molecule was administered at different times of day and night and, as expected, the optimal timing fluctuated over an eight-hour span. “The same dose was three to five times more toxic depending on the time of administration,” says Lévi. Using quantitative polymerase chain reaction (PCR), the team then analyzed, inside mouse liver and colon cells, the 24-hour rhythm of expression of 27 genes involved in the body’s chronobiology, cell-cycle, and drug metabolism. After analyzing the data, they developed an algorithm which showed that two core clock genes, namely Rev-erbα and Bmal1, could be used to predict the optimal timing for administering irinotecan, regardless of the mouse’s gender and genetic background. “When you know how both of these genes are expressed over the day in an individual, you can predict when drug administration will be less toxic and most effective,” says Lévi. Dimer. Two bonded similar monomers.


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