Regulating the traffic of amino acids entering cancer cells can make them more sensitive to chemotherapy: this is what emerges from the study carried out with the support of the Airc Foundation by the Ifom researchers and the University of Milan coordinated by Marco Foiani, head of the program 'Integrity of the Genome' of Ifom and scientific director of the same Institute. The results, published in the journal Developmental Cell, may pave the way for new personalized therapeutic strategies.
"For over 15 years - explains Foiani - our research group has been investigating how the metabolic conditions of the cell, also influenced by our nutritional regime, can affect the stability of the genome". Previously, the researchers found that the Beclin protein plays a crucial role in influencing the cell's response to chemotherapy drug-induced DNA damage, but it was unclear how and why. "What has now emerged from our research carried out by combining approaches of genetics, metabolomics and proteomics - continues Foiani - is that Beclin's protective function is due to the influence it exerts on the transport of amino acids at the cell membrane level".
"In particular - explains Arta Ajazi, first author of the article - Beclin's loss of function involves a significant increase in the transport of various amino acids, including tryptophan and leucine, from the external environment to that inside the cell. Once entered the cell, these amino acids are essential to produce proteins that allow cells to repair DNA, allowing cells to survive the stress caused, for example, by chemotherapy drugs. This effect may explain the ability of cells, mutated in the gene that encodes Beclin, to resist chemotherapy drugs. "
The result could allow patients to be treated with personalized medicine approaches avoiding chemotherapy where genomic testing reveals Beclin mutations.
The next step will be to develop treatments that combine chemo with nutritional supplements to influence the concentration of amino acids in the environment where the tumor grows.
