KRAS mutations have long been considered undruggable. However, a series of direct KRAS mutation inhibitors have been developed since the switch II pocket was discovered recently. This review will summarize progress in the development of direct KRAS G12C mutation inhibitors, current relevant drugs under study and challenges that need to be considered in future research.
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http://dx.doi.org/10.3389/pore.2021.631095 | DOI Listing |
Mol Cancer
January 2025
Department of Physiology, College of Medicine, National Cheng Kung University, Tainan, Taiwan.
Background And Aims: Oncogenic KRAS mutations are present in approximately 90% of pancreatic ductal adenocarcinoma (PDAC). However, Kras mutation alone is insufficient to transform precancerous cells into metastatic PDAC. This study investigates how KRAS-mutated epithelial cells acquire the capacity to escape senescence or even immune clearance, thereby progressing to advanced PDAC.
View Article and Find Full Text PDFJ Gastrointest Oncol
December 2024
Department of Biliary-Pancreatic Surgery, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
Background: In recent years, the incidence of pancreatic cancer has shown an obvious increasing trend worldwide and even causes a greater disease burden to the mankind. Due to the lack of effective early surveillance methods, patients are often in the middle to advanced stages of their disease at the time of detection, thus losing the opportunity for surgery. The currently available chemotherapy regimens are yet to be further improved to prolong patient survival.
View Article and Find Full Text PDFAnn Surg Oncol
January 2025
Division of Surgery, Department of Surgical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
Pancreatic cancer has a poor prognosis despite ongoing advances in systemic and multimodal therapies. This review analyzes recent progress and future directions in pancreatic cancer clinical trials, emphasizing the evolution from traditional approaches to a more personalized and biologically-driven treatment paradigm. While improvements in overall survival have been achieved through perioperative therapies, gaps remain in our understanding of optimal treatment strategies.
View Article and Find Full Text PDFMol Ther
January 2025
Department of Hepatobiliary and Pancreatic Surgery, the First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China; Key Laboratory of Pancreatic Disease of Zhejiang Province, Hangzhou, China; Innovation Center for the Study of Pancreatic Diseases of Zhejiang Province, Hangzhou, China; Zhejiang Clinical Research Center of Hepatobiliary and Pancreatic Diseases, Hangzhou, China; Cancer Center, Zhejiang University, Hangzhou, China. Electronic address:
KRAS mutations are instrumental in the development and progression of pancreatic ductal adenocarcinoma (PDAC). Nevertheless, the efficacy of direct targeting of KRAS mutations to inhibit tumor development remains doubtful. It is therefore necessary to gain a deeper insight into the mechanism in which KRAS mutations influence the effectiveness of clinical treatments.
View Article and Find Full Text PDFBiol Direct
January 2025
Department of General Surgery, The First Affiliated Hospital of Xi'an Jiaotong University, 277 West Yanta Road, Xi'an, Shaanxi, 710061, China.
Pancreatic cancer is a lethal disease with an insidious onset, and little is known about its early molecular events. Here, we found that the sterol regulatory element-binding protein 1 (SREBP1) expression is gradually upregulated during the initiation of pancreatic cancer. Through in vitro 3D culture of pancreatic acinar cells and experiments in LSL-Kras;Pdx1-Cre (KC) mice, we found that pharmacological inhibition of SREBP1 suppressed pancreatic tumorigenesis.
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