Kirsten Rat Sarcoma Viral Oncogene Homologue (KRAS) Mutations in the Occurrence and Treatment of Pancreatic Cancer

Author(s): Ziying Zhu, Saisong Xiao, Haojie Hao*, Qian Hou*, Xiaobing Fu*.

Journal Name: Current Topics in Medicinal Chemistry

Volume 19 , Issue 23 , 2019

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Graphical Abstract:


Abstract:

Pancreatic cancer is a highly malignant tumor with a 5-year survival rate of less than 6%, and incidence increasing year by year globally. Pancreatic cancer has a poor prognosis and a high recurrence rate, almost the same as the death rate. However, the available effective prevention and treatment measures for pancreatic cancer are still limited. The genome variation is one of the main reasons for the development of pancreatic cancer. In recent years, with the development of gene sequencing technology, in-depth research on pancreatic cancer gene mutation presents that a growing number of genetic mutations are confirmed to be in a close relationship with invasion and metastasis of pancreatic cancer. Among them, KRAS mutation is a special one. Therefore, it is particularly important to understand the mechanism of the KRAS mutation in the occurrence and development of pancreatic cancer, and to explore the method of its transformation into clinical tumor molecular targeted treatment sites, to further improve the therapeutic effect on pancreatic cancer. Therefore, to better design chemical drugs, this review based on the biological functions of KRAS, summarized the types of KRAS mutations and their relationship with pancreatic cancer and included the downstream signaling pathway Raf-MEK-ERK, PI3K-AKT, RalGDS-Ral of KRAS and the current medicinal treatment methods for KRAS mutations. Moreover, drug screening and clinical treatment for KRAS mutated cell and animal models of pancreatic cancer are also reviewed along with the prospect of targeted medicinal chemistry therapy for precision treatment of pancreatic cancer in the future.

Keywords: Pancreatic cancer, Drug screening, KRAS mutations, Chemistry drugs, Precision treatment, Malignant tumor.

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VOLUME: 19
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Year: 2019
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