The adenocarcinoma pancreatic represents the 85% of pancreatic tumors diagnosed. It is associated with a dismal prognosis, due to its late diagnosis and its resistance to most available treatments. Therefore, it is essential understand the cellular and molecular mechanisms involved in this type of pancreatic cancer in order to develop more effective therapeutic strategies.
Researchers from the Cima University of Navarra have identified an important gene in the development of pancreatic adenocarcinoma. Its study in human samples and experimental models guides the development of possible therapeutic strategies for patients with this disease. The results of this work have been published in “Clinical Cancer Research”, a leading journal in the field of oncology.
«This pancreatic cancer is characterized by multiple genetic alterations, among which is the oncogen KRAS. In previous studies, we described a gene signature common to tumors of the lung, pancreas, colorectal cancer, and cholangiocarcinoma, which included the gene LAMC2.
“In this work we have studied its function in pancreatic adenocarcinoma and confirmed that it is increased in early stages of tumor development and in established tumors. Likewise, LAMC2 plays a relevant role in the proliferation and growth of this cancer, both in three-dimensional conditions and in vivo”, explains Silve Vicent, a researcher at the Cima Solid Tumor Program and co-director of the study.
On the other hand, the study shows that deletion of the gene significantly reduces tumor growth, which is why it is presented as a possible therapeutic target for the disease.
combined treatment
By analyzing the molecular mechanisms of LAMC2, the researchers have shown that it carries out its function through genes that are susceptible to a pharmacological approach, such as AXL. «to increase success As a possible treatment, we combine inhibitors of this gene with other therapies that have been tested in clinical trials in pancreatic cancer (MEK inhibitors). We see that this combination is effective in 3D cultures derived from patient and mouse tumor samples.”
Deletion of the gene significantly reduces tumor growth, which is why it is presented as a possible therapeutic target of the disease.
The next step will be iidentify patients that could benefit better from this combination according to their molecular characteristics. “A project of this type can serve as a preclinical basis to try to advance in its clinical application and encourages us to continue in this line to propose a study with this combination in patients with pancreatic cancer,” says Mariano Ponz Sarvisé, a specialist in Medical Oncology from the University of Navarra Clinic.