This is how the wick of pancreatic cancer is lit
Pancreatic cancer is one of the deadliest tumors. The survival rate for pancreatic ductal adenocarcinoma, the most frequent form of the disease, stands at 8.6%, the lowest percentage of all common tumors, according to data from the Spanish Society of Medical Oncology.
Much is still unknown about this tumor, which is often diagnosed when it is already in advanced stages, although research is progressing. The latest noteworthy novelty is signed by a team with Spanish participation that has managed to reveal why the wick of this type of cancer begins. Details of the process are published in the latest issue of the journal Science.
It has been known for some time that in pancreatic tumors, as in other types of cancer, mutations in the KRAS oncogene are key.. The team that is now publishing news about the disease, made up of researchers from the Memorial Sloan Kettering Cancer Center (MSKCC) in New York, and the researcher Direna Alonso-Curbelo, who now works at the Barcelona Institute for Research in Biomedicine (IRB), He also previously demonstrated the inducing role of external factors such as tissue injury that causes inflammation (such as pancreatitis) in triggering the disease.. And now, scientists have shown that cellular plasticity, the ability of some cells to change identity in response to genetic alterations or the influence of external stimuli, is also critical to the process.
The interactions between genetic mutations and external factors, emphasize the researchers, modify the identity of some cell subpopulations, transform them. And, as a consequence of this, the ability of these cells to communicate and interact with other cells in their environment is greatly increased, which contributes to the development of cancer.
Specifically, scientists have shown that in the earliest stages of pancreatic cancer there are diverse cell subpopulations that have high plasticity and are more sensitive to the oncogenic action of KRAS and non-genetic factors (pancreatitis) that predispose to cancer.. According to their data, these cells have, on the one hand, a different and specific epigenome; and, on the other, an increased capacity to be able to respond and send signals to their environment.
Driven by the influence of mutations and inflammation, these cells generate aberrant communication networks, triggering a feedback loop that leads to cancer development and progression.
Pancreatic ductal adenocarcinoma cells, the most common type of tumor in this organ.
“Our work is designed to deepen our knowledge of pancreatic cancer, but having identified and unmasked the characteristics of these cells with a greater propensity to change their identity, more plastic, can serve as a guide to find useful molecules against this type of cancer” , says Alonso-Curbelo, co-lead author of the study.
In mouse models, the team showed that it was possible to block the aforementioned aberrant communication and that these conversations between cells played a fundamental role in the development of cancer.. “Our analyzes demonstrated that these expansive communication networks established in the early stages of pancreatic cancer are functionally relevant and direct pancreatic tumorigenesis in mice”, adds the researcher, who stresses that the work has been possible thanks to an interdisciplinary team.
Thus, the research combined sophisticated genetically modified mouse models and advanced computational methods to map the various cellular states that lead to cancer and unravel the characteristics of individual pancreatic cell subpopulations at each stage of tumor progression.
The computational area of the research has been directed by Cassandra Burdziak, a doctoral student in the laboratory of Dr.. Pe'er, at the MSKCC; while the experimental and conceptual part has been led by Alonso-Curbelo herself, who began the research during her stay at the New York institution, in Scott Lowe's laboratory (MSKCC).
mRNA vaccines against pancreatic cancer
On the other hand, an article published this week in Nature has shown promising results from an experimental vaccine based on messenger RNA technology, the same one that was used in vaccines against Covid-19, against the most aggressive pancreatic cancer.
The results of a phase I clinical trial show that personalized vaccines are capable of inducing an immune response against cancer.
The authors of the study, also researchers at the Memorial Sloan Kettering Cancer Center in New York, administered a personalized mRNA vaccine to 16 patients with ductal pancreatic adenocarcinoma in the first phase of clinical research. The first results of a clinical trial with 16 volunteers have shown that the vaccine induces substantial immune response and potentially delays relapse of patients in a form of cancer, since they were made with neoantigens identified in their own tumors. The treatment was administered in combination with chemotherapy and immunotherapy.
In eight patients, the researchers observed an increase in T cells against the antigens administered in the vaccine.. These same patients had not experienced a reactivation of their cancer at 18-month follow-up, while the eight patients for whom the therapy did not work relapsed on average 13 months after surgery.
“The study is very well designed and its scientific quality is unquestionable.. It demonstrates something that has been suggested many times before (with less robust data), namely that personalized vaccination with mRNA of tumor antigens is effective in inducing a response and that it can, at the very least, increase survival times.. This work confirms that it can generate responses with clearly very reduced adverse effects against one of the tumors with the highest mortality, pancreatic ductal adenocarcinoma”, Manel Juan, head of the Immunology Service at the Hospital Barcelona Clinic.
The most important limitation of the work, continues the specialist, “is that the sample size (of treated patients) is clearly very small and with a single branch design without randomization. In any case, once the safety of the proposal has been confirmed, it seems that the next step to study is to see if simply advancing this 'vaccination' before giving the checkpoint inhibitor [the other type of immunotherapy used] may be more reasonable. and it may allow for better clinical results than vaccinating after administering the antibody, as has been the case (probably as an ethical criterion of first giving the treatment that has demonstrated certain functionality, although it makes less sense pathophysiogenically).. In any case, it is an important contribution to the area, although we cannot give it as disruptive or definitive.”