PLOS: PDX can be Used as an Ideal Research Model for Advanced Pancreatic Cancer

Pancreatic ductal adenocarcinoma is cancer with a very high mortality rate. This disease is aggressive and can metastasize rapidly. Therefore, pancreatic ductal adenocarcinoma is still a very difficult to treat clinically. A better understanding of the pathogenesis, invasion, and metastasis mechanism of pancreatic ductal adenocarcinoma will significantly promote the development of therapeutic drugs and treatment methods. However, there is still a lack of ideal disease models that can represent advanced stages of cancer. In addition, the molecular similarity between PDX animal models used in preclinical cancer research and orthotopic patient tumors remains unknown.

To identify potential driver molecules in the progression of metastatic pancreatic cancer, scientists from the United States and Spain performed whole-exome sequencing on orthotopic tumors, metastases, and standard samples (peripheral blood) from an autopsy project. At the same time, the Corresponding PDX models were also constructed, sequenced and compared to patient tumors.

After analyzing sequencing data from three patients, the researchers found an average of 160 single-nucleotide mutations in each tumor sample. Most of the patients' mutations present in tumors in situ and metastases. Most importantly, these mutations were also preserved mainly in the PDX models.

Based on the mutation rates of tumors in situ and metastases, the researchers proposed that there may be a clonal evolutionary pattern in which functional mutations affect some important oncogenes, such as KRAS, TP53, and SMAD4, which all in It play an essential role in tumor development and metastasis.

This study deepens our understanding of the biology of pancreatic tumors and also shows that PDX models derived from advanced patient tumor tissue can well represent the genetic characteristics of the disease. Hence, PDX models are up-and-coming and can be used to develop effective preclinical research platform for targeted therapy strategies.