2024-02-08 06:19:00
Pancreatic cancer, one of the mechanisms of resistance to therapy discovered
One of the mechanisms of resistance to therapy by pancreatic cancer has been discovered, a killer cancer that often leaves little chance of recovery. The tumor escapes treatment by implementing a ‘favorable genetic mix’, thus playing its best cards to evade treatment. It is the result of a study published today in the journal “Cell Reports Medicine”, coordinated by Professor Claudio Sette, Professor of Human Anatomy at the Catholic University, and Director of the “Organoids Facility” at the Fondazione Policlinico Universitario A. Gemelli IRCCS.
“We have discovered a mechanism based on the regulation of messenger RNAs that contributes to chemotherapy resistance – explains Professor Sette – RNA drugs already exist, used with other medical indications, to counteract this type of regulation, which could therefore also be developed as anti-tumor agents with ad hoc tests on resistant patients”. Pancreatic cancer affects approximately 500 thousand people worldwide every year; despite being the 14th cancer in terms of incidence, it is unfortunately currently the seventh cause of death from cancer.
Indeed, survival 5 years after diagnosis is less than 10%, almost exclusively restricted to patients who can be operated on (approximately 20-30% of the total). When the genetic code is transcribed into RNA and then proceeds to protein synthesis, what is called “alternative splicing” can occur, i.e. different transcripts can be produced from the same gene depending on the ‘genetic cards’ (exons, i.e. the part of the gene coding for the amino acids of proteins) that are chosen ‘to be played’. Splicing therefore leads to the production of different proteins that play different roles, through the alternative assortment of exons present in the starting gene. Splicing is generally altered in tumors, including pancreatic cancer.
“By comparing pancreatic tumors of different subtypes – explains Professor Sette – we have seen that the treatment-resistant neoplasm is associated with a very precise regulation of splicing, which leads precisely to the synthesis of proteins associated with chemoresistance. Our study, funded by the Italian Association of Cancer Research, has also identified a splicing regulator, called ‘Quaking’, which is expressed in the most aggressive pancreatic tumors and which with its action promotes the synthesis of proteins that trigger chemoresistance ”. Currently, splicing-regulating drugs already exist which could therefore also be used for this tumor. There are also specific therapies for individual splicing events, such as the drug Nusinersen used in spinal muscular atrophy. “Our discovery therefore opens up new treatment possibilities for a type of tumor that generally does not respond to existing therapies,” concludes the professor.
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