Tissue-invading tumors are a leading cause of death worldwide, with nearly ten million deaths a year caused by progressive resistance to cancer treatments. In breast cancer, for example, aggression is linked to the progressive fibrotic tightening of the tumor tissue, which prevents drugs from reaching diseased cells. To tackle the problem, it is necessary to understand how the fibrotic microenvironment that forms around cancer cells evolves, with the ultimate goal of designing increasingly targeted anticancer therapies.
Evolution of the tumor involves many types of cells and signals, and is impossible to realistically reproduce in the laboratory. To advance knowledge of the sector, we are working on a project funded by the European Research Council (ERC). We are developing an innovative platform capable of reproducing tumor fibrosis by exploiting the vascularization of a living organism. In short, we adhere human breast cancer cells to microscopic polymer substrates to create models of tumor microenvironments. We implant the microenvironments in the respiratory membrane of embryonated chicken eggs to elicit a fibrotic reaction around the cancer cells. To validate the platform, we measure the efficacy and specificity of drugs, for example chemotherapy, already approved for use on patients, on microenvironments.
This project provides new knowledge on tumor progression mechanisms, but also an ethical and standardizable platform to promote the clinical translation of new therapeutic products into oncology. The platform allows to overcome one of the main problems that characterized the cultivation of human tissues in the laboratory in the past: realistically reproducing the circulation of blood capillaries.
The idea on how to solve this problem was born in the mechanobiology laboratories of the Politecnico di Milano, where we count in five years to obtain a validated and ready platform for testing new therapeutic agents in the pharmaceutical industry. Realism is only one of the advantages of the proposed technology. The development of a new drug takes an average of thirteen years and costs three billion euros, a value that has increased by 70 percent in the last ten years. This is because the success of a new drug achieved in the laboratory is almost never confirmed in the animal.
This ERC-funded project contributes to creating a laboratory platform, but also a living and humanized one, able to better identify the most promising therapeutic strategies, and therefore drastically reduce the costs and time for the development of new oncological drugs.