One of the most promising therapeutic strategies for cancer patients is constituted by molecular target therapies, i.e. those that deliver the drug specifically against cancer cells that bring a certain target to the surface: these therapies guarantee greater precision and less toxicity than to traditional chemotherapies. However, the effectiveness of these therapies is unfortunately limited by the development of tolerances and resistances on the part of tumors, which can thus cause metastases.
Relapses and metastases
The development of metastases and resistance to therapy are the main cause of relapses in cancer patients. In some cases the relapse is rapid, and is due to genetic alterations already existing in the tumor mass before the administration of the treatment. In other cases, however, the tumor reappears after a long time, even years after diagnosis, and it is not known how and why. The ability to prolong the effectiveness of a treatment is currently limited by the lack of knowledge of the multiple mechanisms that lead to the development of resistance.
Cancer: do we all really have the best therapies available?
by Daniela Minerva
Understanding exactly how tumors are able to resist therapy is therefore a crucial question to be answered in order to be able to defeat them, making targeted therapies more effective and offering patients superior quality and life expectancy. A significant step forward in this direction was marked by the results of a study, just published in the authoritative scientific journal Nature Genetics.
The Italian study that combines mathematics and biology
The study was conducted in collaboration with Ifom, the University of Turin, the University of Milan and the Candiolo Cancer Institute Fpo IRCSS by researchers led by professors Marco Cosentino Lagomarsino and Alberto Bardelli thanks to the support of the Airc foundation and a grant Erc of the European Union.
The interdisciplinary group made up of physicists and biologists investigated the resistance to molecularly targeted therapies from a quantitative point of view and with a novel approach that combines mathematics with biology. More precisely, thanks to mathematical tools, tumor cells have been characterized in their various subpopulations, reaching exceptional levels of detail and depth.
“We have adopted – he explains Marco Cosentino Lagomarsino, by Ifom and the University of Milan – a method very similar to that originally used, in 1943, by Salvador Luria and Max Delbrück to study the development of resistance in bacteria. That pioneering experiment gave a fundamental impetus to modern experimental genetics and proved crucial to the development of molecular biology, to the point that the two scientists were awarded the Nobel Prize for Medicine in 1969. The same approach, however, had so far been used in a very limited way. in human cells, probably due to the complexity and duration of the experiments required. In fact, it is necessary to sample and characterize many cells, in our case obtained from patients with colorectal cancer, both during drug treatment and in normal growth conditions “.
Hit the Braf mutation to cure many cancers
by Fabio Di Todaro
“The results obtained with the laboratory experiments were enriched by the mathematical analyzes and vice versa – he adds Alberto Bardelli, of ifom and the University of Turin – and the collaboration was essential for the success of this project. On the one hand, preliminary theoretical considerations based on mathematical models allowed us to design the experiments in an optimal way for our purposes. On the other hand, the results of the experiments in genetics and molecular biology have allowed us to apply mathematical models to think about innovative treatment protocols, which could lead in perspective to a reduction in resistance to therapies “.
Therapies and the ‘lethargy’ of cancer cells
What did the researchers highlight in the laboratory? “We observed – he says Mariangela Russofirst author of the article, from the University of Turin and Candiolo Cancer Institute – that molecularly targeted therapies induce the transition to a state of lethargy in cancer cells, making them able to temporarily tolerate the treatment “.
Tumors, here is the first atlas of all mutations
by Dario Rubino
“These cells, precisely called ‘persistent’, being tolerant to therapy, potentially have time to acquire genetic mutations that make them able to replicate in the presence of the drug, thus causing a relapse of the disease. Our studies – he concludes – have allowed us to understand that the therapy induces a significant increase in the ability of persistent cells to mutate: not only do persistent cancer cells have time to develop mutations in their favor, but the therapy makes this process faster “.