Cancer beats chemotherapy as in a game of poker, choosing its cards from those that are continually reshuffled by genetic instability caused by the presence of an altered number of chromosomes in cells: this is demonstrated by an international study coordinated by Stefano Santaguida dell ' European Institute of Oncology (Ieo) and of the State University of Milan.
The results of the research, also supported by the AIRC Foundation, are published in the journal Developmental Cell.
"Our work makes a fundamental contribution to understanding the causes of chemoresistance, a risk that hangs over even the most effective anticancer drugs", explains Santaguida. "We have shown that the cancer cell is capable of exploiting its genetic instability to survive even in stressful conditions, such as the fatal attack of a chemotherapy drug. It all starts from aneuploidy, a change in the number of chromosomes, which results in a chromosomal patrimony (karyotype) different from normal cells and characterized by genetic instability.
This instability is at the basis of the 'cellular chaos' characteristic of cancer, which disrupts the normal functioning of the cell. as if the cells were continually 'shuffling the cards'. This continuous shuffling can be exploited by a tumor cell to survive: continually turning its genetic makeup upside down, when attacked by a chemotherapy molecule it can better select its 'poker of aces', that is, the karyotype capable of resisting. to the drug. This explains why in some patients chemotherapy may not achieve the desired results ".
Aneuploidy is present in 90% of solid tumors and 75% of haematological ones. "Our goal - says Santaguida - is to include karyotype analysis in the study of the tumor profile", a step forward "towards precision medicine. If we identify which karyotype causes chemoresistance, we can immediately understand which combination of drugs to use. to avoid it and provide treatments capable of eradicating cancer cells ".
