Currently, surgery is the sole treatment for pancreatic cancer; however, only 15–20% of individuals are diagnosed with resectable tumors. In addition, up to 80% of individuals with resected tumors experience recurrence. Prognosis and treatment decisions for pancreatic ductal adenocarcinoma are currently hindered by the lack of reliable biomarkers (PDAC).
Endoscopic ultrasound-guided fine needle aspiration (EUS-FNA) is still the gold standard for diagnosing localized PDAC, with a sensitivity of approximately 85% and a specificity of nearly 100%. It can also be utilized to produce tissue for cytological and even histological diagnostics, as well as for other purposes such as KRAS identification.
The RAS/MAPK pathway is regulated by the KRAS proto-oncogene. KRAS exists in both its “wild type” and its “mutated” forms. Several types of cancer are linked to mutations in the oncogene KRAS. When the amino acid glycine is altered, the KRAS protein develops oncogenic features that cause the growth, proliferation, and progression of cancer. The many mutations at codon 12 are only partially understood.
The molecular landscape of pancreatic cancer is very well defined in recent years. KRAS, TP53, CDKN2A, and SMAD4 are the four genes that experience mutations with the highest frequency in pancreatic cancer. There is a correlation between mutations in these genes and oncogenic cellular processes in pancreatic cancer as well as the prognosis of the disease.
Kras Mutation Pancreatic Cancer – g12c, g12d, g12r
The KRAS (Kirsten rat sarcoma viral oncogene) homolog is connected to various aggressive types of the disease and is the oncogene that is mutated in human cancers at a higher frequency than any other (CRC). Because of its role in the development of cancer in Kirsten RAt Sarcoma virus, this mutation is commonly referred to as KRAS. KRAS often acts as a communication hub for signals in the cell that promote cell proliferation.
The discovery of tumor driver genes and the creation of particular inhibitors significantly result in changed cancer therapy techniques and clinical outcomes. PDAC (pancreatic ductal adenocarcinoma) mutations in KRAS are almost often missense mutations, and the majority of them are found at codon 12. KRAS mutations are mostly classified into G12D, G12V, G12R, G12C, G12A, and G12S based on the distinct bases of missense mutations. The G12D mutation is the most prevalent KRAS mutation.
KRAS G12R is a predictive biomarker for the treatment of patients with dacomitinib, afatinib, erlotinib, gefitinib, osemertinib, cetuximab, and panitumumab. It has been revealed that the mutant KRAS G12D is partially responsible for the metabolic phenotype of pancreatic cancer cells via altering anabolic glucose metabolism.
The KRAS G12C mutation acts as a driver for several different forms of cancer. Some of the most prevalent and lethal carcinomas, such as lung, colorectal, and pancreatic cancers, are impacted by KRAS mutations. KRAS G12C is the most common kind of KRAS mutation, accounting for approximately 44% of all KRAS variants.
The two most prevalent KRAS mutations are G12D and G12V. Typically, KRAS operates like a light switch, switching between “on” and “off.” When active, the protein transmits signals instructing the cell to proliferate and divide. However, when the protein is mutated, it rarely turns off, resulting in uncontrollable cell growth.