Cancer cells build real barriers that prevent drugs from hitting them. An international group of researchers, coordinated by Stefano Santaguida of the European Institute of Oncology and of the State University of Milan, focused on this mechanism of chemoresistance of cancer cells which has not yet been identified. This is the mechanism by which the cancer cell builds a barrier capable of blocking the action of anti-cancer drugs, making it ineffective.
At the origin of the feared phenomenon, the study reveals, there may be a known chromosomal anomaly called “aneuploidy”, or a variation in the number of chromosomes, present in most cancers. The results of the research, also supported by the AIRC Foundation, have just been published in the prestigious scientific journal Developmental Cell.
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“Our work makes an important contribution to understanding the causes of chemoresistance, a risk that hangs over even the most effective anti-cancer drugs – he explains. Stefano Santaguida, Group Leader of the IEO Genomic Integrity Laboratory and Professor of Molecular Biology at the University of Milan – We have shown that the tumor cell is capable of exploiting its own genetic instability, thus surviving even in conditions of important stress, such as fatal attack of a chemotherapy drug. Everything seems to start from aneuploidy, a change in the number of chromosomes, which results in a chromosomal heritage (or karyotype) different from normal cells and characterized by genetic instability. This instability underlies the “cellular chaos” characteristic of cancer, which disrupts the normal functioning of the cell. It is as if the cells are constantly “shuffling the cards”. This continuous mixing can be exploited by a cancer cell, which thus survives. By continually upsetting her genetic makeup, when attacked by a chemotherapy molecule she can better select her ‘poker of aces’, that is, the karyotype capable of resisting the drug. This may explain why chemotherapy sometimes does not achieve the desired results in some patients. “
Aneuploidy is present in about 90% of solid tumors and in 75% of haematological ones and has long been the subject of study by the Santaguida group, first as a target to target the tumor and now also as a tool to combat drug resistance.
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To test the effects of chromosomal instability on cell proliferation in the presence of a chemotherapy agent, the researchers exposed cultured tumor cells to a battery of chemotherapy drugs, comparing the results before and after exposure.
“We used different types of cultured cancer cells, obtained from different types of cancer, including colon, lung and pancreas. The cells were continuously exposed to the antitumor agents routinely used in the clinic,” he says. Marica Ippolito, first author of the study and PhD student in Molecular Medicine at IEO – Among the conditions tested, we found combinations that offered an advantage to these cells, in terms of survival, in about one in five cases. ”
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“The clinical implication of our discovery is very relevant – concludes Santaguida – Our goal is to include the analysis of the karyotype in the study of the tumor profile, which we already carry out today and which allows us to obtain a more precise treatment. The patient-by-patient study. karyotype of cancer cells, if confirmed in preclinical and clinical studies, could be a further step towards a more effective and precise medicine. If we identify which karyotype causes chemoresistance, we can immediately understand which combination of drugs to use to avoid this phenomenon and provide treatments better able to eradicate cancer cells Data from world cancer research confirm that to find the cure for cancer, the magic pill, we need to know the inside of the cancer cell, that is, what happens inside it at the molecular level. Our study goes exactly in this direction “.
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