Pancreatic cancer: in each patient many different tumor cells, which complicate therapies

Pancreatic cancer: in each patient many different tumor cells, which complicate therapies

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Oncology research has made incredible progress in many fields. But unfortunately there are tumors for which this is not true. One above all, that of the pancreas. The most modern drugs, such as immunotherapies and molecularly targeted therapies, are struggling to make their way in the treatment of this neoplasm. And the result is that there has been no improvement in the long-term survival rates of patients with pancreatic cancer for nearly 50 years.

How come? An important clue could be given by a recent study carried out by researchers from the European Institute of Oncology (Ieo), the Ifom – the Institute of Molecular Oncology of the Airc Foundation and Humanitas, which details a profound heterogeneity within the populations of cells that make up every single pancreatic tumor, a possible explanation – write its authors in Cancer Cell – for the poor effectiveness of existing treatments.

The tumor

Pancreatic cancer is a relatively common neoplasm: it is estimated that in 2022 there were more than 14 thousand diagnoses in our country. As we were saying, it is a tumor for which there are still very few therapeutic options, and for which the prognosis is therefore rather poor. To date, it is the neoplasm with the worst survival both one year after diagnosis (34% in men and 37.4% in women) and five (11% for men and 12% for women).

It is suspected that the risk of developing the neoplasm is influenced by cigarette smoking (in this case it is a certainty, given the twice higher incidence among smokers), by the abuse of alcohol and coffee, a sedentary lifestyle, obesity, and clearly by genetic and environmental factors.

Pancreatic cancer is expected to become the second leading cause of cancer death in the world by 2030, given that mortality, unlike what happens with almost all the most common neoplasms, has remained stable for decades, mainly due to poor availability of effective pharmacological therapies. For this reason, the study of the cell populations that make up the tumor (and in particular its most widespread form, pancreatic ductal adenocarcinoma) is considered a particularly interesting field, because it has been demonstrated that greater histological heterogeneity is correlated with the outcome of treatments, and knowing better the tumor cell populations that make up pancreatic tumors, and their behavior, could help develop new, more effective therapies.

I study

“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 ” points out Giuseppe Diaferiacoordinator, together with Giacchino Natoli, of the IEO research group that carried out the study. “We used innovative technologies for the targeted isolation of small groups of tumor cells and their molecular profiling, and combined them with computational analyzes and artificial intelligence approaches. We were thus able to define this heterogeneity, so that it can become the target of targeted therapies”.

The work, therefore, lays the foundations for the identification of cell populations that develop dynamically within pancreatic tumors, towards which in the future it will be possible to direct the development of new therapeutic strategies. Also – suggest the authors of the study – using artificial intelligence approaches, which could help analyze normal histological preparations, to establish the composition of the tumor and guide the doctor in choosing the most appropriate combination of drugs for each patient.

Furthermore, of particular importance was the discovery of a correlation between specific gene expression programs and the invasion of the nerves, which for pancreatic cancer represent a sort of escape route through which the neoplasm’s cells can reach other tissues of the the organism and give rise to metastases.

“Understanding the heterogeneity of pancreatic cancer is crucial to developing effective therapeutic strategies,” concludes Natoli. “Although 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 for targeted therapeutic approaches that will finally offer new hope to patients facing this difficult disease.”

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