Cancer is a dark side of life. A tumor cell is just a healthy cell in which genetic programming has changed, allowing it to reproduce faster, generate a primary tumor, move through the body and generate secondary tumors, the metastasis which causes 90% of cancer deaths. For all this, the disease uses biological mechanisms identical to those that allow a healthy living being to grow.
This plasticity can also be a weak point, as shown in a study published on Monday. The work is a proof of concept, the preliminary demonstration that the process of cancer evolution can be reversed.
The study has shown that the combination of two drugs – the antitumor drug Trametinib and the antidiabetic drug Rosiglitazone – transforms the cells of the breast cancer in harmless fat in mice that had been grafted with breast tumors with patient metastases. Triple-negative tumors, the most aggressive type of breast cancer that does not respond to treatments based on hormone receptors, have been used in the study.
The key to the study has been to attack the cancer at a time when the tumor cells perform the so-called epithelial-mesenchymal transition. This metamorphosis is fundamental for the development of an embryo and the formation of the different organs and tissues of a healthy body. It also plays a role in tumor proliferation, as it helps epithelial tumor cells that are fixed to a tissue to become mesenchymal, allowing them to detach and move through the bloodstream. Within breast tumors, these cells are responsible for disseminating cancer to other organs.
The fat cells can not multiply, so that after the transformation the tumor can not grow
Dana Ronen, University of Basel
The study, published in Cancer Cell, shows how the combination of the two drugs slows down the proliferation of the original breast tumor and also the metastasis. According to the work, this is because the drugs interfere in the transition by transforming cancer cells into adipocytes (fat).
"By definition, fat cells can not multiply to generate daughters, so after the transformation the tumor can not grow, it's like a dead end," explains Dana Ronen, a researcher at the University of Basel and co-author of the study. "The transformation into fat only affects the outermost cells of the tumor, which are responsible for moving and causing metastasis, so it should not have a negative effect on health nor have we observed changes in the weight of the animals. The rest of the cells of the primary tumor become more differentiated, which possibly makes them more vulnerable to other treatments such as hormone therapy, "he points out. Now, the team wants to study if this same strategy works with other tumors and if it can also help animals that have already metastasized.
"These are very preliminary results, but they are important because they represent a new novel therapeutic path", says Miguel Ángel Quintela, director of the breast cancer unit of the National Center for Oncological Research (CNIO). "The logical thing is to continue investigating. There is a good base to take it to humans because only two drugs are needed already approved for other uses, both with low toxicity, "says Quintela.
"One of the drugs we have used, Trametinib, is very expensive, so we hope that this work will arouse the interest of some of the pharmaceutical companies that manufacture it so that they can finance their study in this type of combination," adds Ronen.