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Physics can show us the interior of tumors.



IMAGE

IMAGE: Dark red indicates the most rigid areas, towards the interior of the tumor. The edge is less rigid (yellow-green).
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Credit: Thomas Dehoux / ILM / CNRS

A team of physicists at the Lumière Matière Institute (CNRS / Claude Bernard Lyon University 1), in collaboration with the Lycan Cancer Research Center (CNRS / INSERM / Claude Bernard Lyon University 1 // Léon Bérard Center / Lyon Hospices civils ), has demonstrated the potential, for oncology, of an imaging technique based solely on the physical properties of tumors. It can differentiate populations of malignant cells and monitor how effective a cancer treatment is. These results, published in Physical revision letters On January 8, 2019, it should help in the design of new therapeutic molecules and in the personalization of treatments.

Despite a good understanding of cancer biology, 90% of experimental drugs fail during clinical trials. It is also increasingly suspected that the mechanical properties of tumors influence the progression of the disease and the effectiveness of the treatment. Although we can evaluate the elasticity of the tumor worldwide, it is more difficult to measure the local stiffness in depth and see if the tumor core resists the penetration of therapeutic liquids. To investigate these physical properties, researchers have used a non-contact imaging technique that does not require the use of contrast agents, therefore, they do not disturb tissue function, which exploits the natural infinitesimal vibrations of matter.

To recapitulate the behavior of colorectal tumors in vitro, the researchers created organoids, spheres with a diameter of 0.3 mm formed by the aggregation of tumor cells. They focused a red laser beam on these objects. The infinitesimal vibrations of the sample, generated by thermal agitation, modify very slightly the color of the beam of light that leaves the sample. By analyzing this light, a map of the mechanical properties of the tumor model is created: the more rigid the area scanned by the laser, the faster the vibrations will be and, in a manner comparable to the Doppler effect (the mechanism that makes a sound mermaid increasingly shrill as it approaches), the greater the change in color.

From organoids composed of two cell lines with different malignant tumors, researchers have shown that they could distinguish the two cell types from their mechanical properties. This information is crucial because it can allow the diagnosis by biopsy analysis to be refined and offer a better evaluation of the tumor grade. Local variations in mechanical properties after pharmacological treatment have also been monitored using this technique: the center of the tumor remains rigid longer than the edge, demonstrating the effectiveness gradient of the treatment. Therefore, local measurement of mechanical properties could confirm the total destruction of the tumor and help to choose the lowest possible treatment dose and duration.

This approach allows us to explore the impact of mechanical properties on the therapeutic response. It should lead to more predictive in vitro tumor models to test new therapeutic molecules and combined therapies, which act, for example, on tissue stiffness to accelerate the penetration of active molecules into the tumor center. It could also provide new indicators to guide clinicians in the customization of therapies.

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