Some fundamental mechanisms underlying pancreatic cancer have been revealed. The discovery by the research group of the European Institute of Oncology coordinated by Gioacchino Natoli and Giuseppe Diaferia, with the collaboration of researchers from Ifom (the Institute of Molecular Oncology of the Airc Foundation) and the Division of Pancreatic Surgery of Humanitas, indicates the possibility of innovative therapeutic approaches for one of the most difficult tumors to treat. The results of the research, supported by the Airc Foundation and the Ministry of Health, are published in the prestigious magazine 'Cancer Cell'.
“Our research has revealed the intricate panorama of pancreatic cancer, clarifying its complexities and highlighting the challenges that persist for its effective treatment. In summary we have identified and characterized in detail – explains Natoli – the profound heterogeneity of each individual pancreatic cancer analyzed. Precisely this heterogeneity contributes substantially to the ineffectiveness of existing treatments”. Pancreatic cancer is expected to become the second leading cause of cancer death in the world by 2030 and already today there is an alarming lack of improvement in survival rates, which have remained essentially unchanged for the last fifty years.
“The coexistence in each pancreatic tumor of populations of tumor cells with different morphological characteristics, i.e. with a different appearance and organization, has been known for some time. However, it has never been possible to establish the impact of this heterogeneity on the treatment of the disease – underlines Diaferia – We used innovative technologies for the targeted isolation of small groups of tumor cells and for their molecular profiling, and we combined them with computational analyzes and artificial intelligence approaches. We were thus able to define this heterogeneity, so that can become the target of targeted therapies”.
“It is as if we were fighting against multiple adversaries at the same time, instead of against a single tumor – adds Pierluigi Di Chiaro, first author of the article – The different cellular conditions that develop dynamically within pancreatic carcinomas require strategies of combined and targeted treatments, capable of intercepting all the populations of neoplastic cells that make up each individual tumor. Our work lays the foundations for the identification of these components and the definition of new strategies”.
“One of the main findings of the study concerns the invasion of the nerves, which constitute real low-resistance escape routes for pancreatic cancer cells. In practice, nerves are the main route of metastatic dissemination, as well as the cause of the severe pain associated with this disease”, warns Lucia Nacci, one of the co-authors of the article. The researchers observed a clear correlation between the activation of specific programs of gene expression and nerve invasion, also revealing potential mechanisms for therapeutic interventions.Finally, the demonstration of the link between the variety of morphological aspects and the different functional properties of tumor cells lays the foundations for the development of artificial intelligence approaches. These new tools could help analyze normal histological preparations – highlights the study – helping to establish the composition of the tumor and guide the doctor in choosing the most appropriate combination of drugs for each patient.
“Understanding the heterogeneity of pancreatic cancer is crucial for developing effective therapeutic strategies – concludes Natoli – Even if this work is the fruit of years of technological optimizations and conceptual advances, it is only a starting point for new research that can pave the way to targeted therapeutic approaches that will finally offer new hope to patients facing this difficult disease.”
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