Pancreatic cancer: a mechanism of resistance to therapy discovered which could be circumvented in the future with new drugs. It is the result of a study, published in the journal Cell Reports Medicine, conducted by experts from the Catholic University of Rome and Policlinico Gemelli Irccs, coordinated by Claudio Sette. Experts have discovered that the tumor escapes chemotherapy drugs by implementing a ‘favorable genetic mix’, thus playing its best cards to evade treatment.
Pancreatic cancer affects approximately 500 thousand people worldwide every year; despite being the 14th type of cancer in terms of incidence, it is unfortunately currently the seventh cause of death from cancer. In fact, survival 5 years after diagnosis is less than 10%. To resist treatment, the tumor uses a genetic mechanism called alternative splicing, that is, it creates genetic templates (the so-called messenger RNAs, the basis for protein synthesis) ad hoc to produce resistance proteins. In practice, thanks to alternative splicing, different proteins can be produced starting from a single gene depending on the messenger RNA that is used as a template. In the case of this tumor, splicing (which is generally altered in tumors, including that of the pancreas) therefore leads to the production of proteins that are resistant to treatment.
“By comparing pancreatic tumors of different subtypes – explains Sette – we have seen that the resistant forms have at their basis, in fact, a very precise splicing, which leads to the production of proteins associated with chemoresistance. Our study, financed by the Italian Cancer Research Association , also identified a splicing regulator called ‘Quaking’ 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 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”, he concludes.
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