Pancreatic cancer is a type of cancer that starts in the pancreas. Pancreatic adenocarcinoma is the most common type of pancreatic cancer. The pancreas is an organ that sits behind the stomach. It´s shaped a bit like a fish with a wide head, a tapering body, and a narrow, pointed tail.

In 2015 pancreatic cancers of all types resulted in 411.600 deaths globally. Pancreatic cancer is the fifth most common cause of death from cancer in the United Kingdom, and the third most common in the United States.

 
The genetic events found in ductal adenocarcinoma have been well characterized, and complete exome sequencing has been done for the common types of tumor. Four genes have each been to be mutated in the majority of adenocarcinomas:
• KRAS (in 95% of cases)
• CDKN2A (also in 95%)
• TP53 (75%)
• SMAD4 (55%)
Transcriptomics analyses and sequencing for the common forms of pancreatic forms of pancreatic cancer have found that 75% of human genes are expressed in the tumors, with some 200 genes more specifically expressed in pancreatic cancer as compared to other tumor types.

 
In more than 95% of cases, the initiating mutation of pancreatic human tumors appears in KRAS, a gene that under normal conditions would prevent cell proliferation. Since its discovery in 1982, the scientific community has published about 36,000 research on this gene and its relationship with cancer, there is still no drug to inhibit its activity when it goes wild.
The nature of the changes that lead to the disease are being intensely investigated, such as the roles played by genes such as KRAS and p53.

 
The study was published this April 9 in Cancer Cell, the complete regression of advanced pancreatic ductal adenocarcinomas in mice is observed, after the combined inhibition of the Epidermal Growth Factor Receptor (EGFR) and the c-RAF kinase.
Ductal adenocarcinoma of the pancreas or ADP is one of the most aggressive forms of pancreatic cancer and one of the most resistant. Its healing occurs in cases in which the tumor can be removed surgically (which is between 10% and 20%).
The results of the study published in Cancer Cell, were presented this Thursday, April 9 in Spain by:

o the biochemist Mariano Barbacid

o Dr. Alfredo Carrato, Head of the Oncology Service of the Ramón y Cajal Hospital in Madrid
o Dr. Marta Puyol, Research Director of the Spanish Association Against Cancer

By simultaneously eliminating the EGFR and c-RAF targets, they found that a significant percentage of tumors not only stopped growing, but disappeared within a few weeks.

The strategy of the biochemist has been to create 12 mice genetically modified to present these same mutations in KRAS and another habitual in another gene, TP53. He then modified the genes of the rodents again to achieve the inhibition of a molecule resulting from the mutation in the KRAS gene – called c-Raf – and the blocking of another of the usual suspects in cancer: the factor receptor of epidermal growth. This has succeeded in inducing cancer and then eliminating it in six of the treated mice.

 
mice with pancreatic cancer
(induced mutations)———-EGFR + RAF——- Blockade of apoptosis—— cancer progression
Inhibited EGFR + RAF——- Apoptosis in 50% of mice– CANCER REGRESSION

Studies of the oncogenic and proto-oncogenic proteins, including Src itself, have proved to be fundamental in unraveling the signaling pathways that control the proliferation and differentiation of normal cells.

The first evidence about the role of cellular oncogenes in human tumors was obtained by gene transfer experiments in 1981. The first human oncogene identified in the gene transfer assays was subsequently identified as the human homolog of the rasH oncogene of the sarcoma virus Harvey.
Three related members of the ras gene family:
– rasH
– rasK
– rasN
they are the oncogenes that are found most frequently in human tumors.
These genes are implicated in approximately 20% of all human cancers, including about 50% of colon cancers and 25% of lung carcinomas.
The ras oncogenes are not found in normal cells; they are generated in tumor cells as a consequence of mutations that occur during the development of the tumor.

Bibliography:

 John P. Neoptolemos et al.; “Pancreatic Cancer”; Ed. Springer Science&Business Media; 2010

 Diane M. Simeone & Anirban Maitra; “Molecular Genetics of Pancreatic Cancer”, Ed. Springer Science&Business Media, 2013

 Geoffrey M. Cooper & Robert E. Hausman; “The cell: A Molecular Approach. Third Edition; Ed. Geoffrey M. Cooper; 2003

Related links

• Cancer cell; Complete Regression of Advanced Pancreatic Ductal Adenocarcinomas upon Combined Inhibition of EGFR and C-RAF
https://www.cell.com/cancer-cell/fulltext/S1535-6108(19)30111-4

• CNIO
https://www.cnio.es/noticias/publicaciones/eliminan-algunos-tipos-de-cancer-de- pancreas-en-modelos-animales/

• Biblioteca Nacional de Medicina EE. UU MedLine Plus
https://medlineplus.gov/spanish/pancreaticcancer.html