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World J Clin Oncol. Aug 24, 2023; 14(8): 285-296
Published online Aug 24, 2023. doi: 10.5306/wjco.v14.i8.285
Targeting KRAS in pancreatic adenocarcinoma: Progress in demystifying the holy grail
Ahmed Elhariri, Ahmed Alhaj, Daniel Ahn, Mohamad Bassam Sonbol, Tanios Bekaii-Saab, Christina Wu, Michael Scott Rutenberg, John Stauffer, Jason Starr, Umair Majeed, Jeremy Jones, Mitesh Borad, Hani Babiker
Ahmed Elhariri, Ahmed Alhaj, Jason Starr, Umair Majeed, Jeremy Jones, Hani Babiker, Division of Hematology-Oncology, Department of Medicine, Mayo Clinic Florida, Mayo Clinic Cancer Center, Jacksonville, FL 32224, United States
Daniel Ahn, Mohamad Bassam Sonbol, Tanios Bekaii-Saab, Christina Wu, Mitesh Borad, Division of Hematology-Oncology, Department of Medicine, Mayo Clinic Arizona, Mayo Clinic Cancer Center, Phoenix, AZ 85054, United States
Michael Scott Rutenberg, Department of Radiation-Oncology, Mayo Clinic Florida, Mayo Clinic Cancer Center, Jacksonville, FL 32224, United States
John Stauffer, Department of Surgical Oncology, Hepatopancreatobiliary Surgery, Mayo Clinic Florida, Jacksonville, FL 32224, United States
Author contributions: Elhariri A and Babiker H designed and wrote the manuscript; Alhaj A, Ahn D, Sonbol MB, Bekaii-Saab T, Wu C, Rutenberg MS, Stauffer J, Starr J, Majeed U, Jones J and Borad M critically reviewed and edited the manuscript; All authors approved the final version of the manuscript.
Conflict-of-interest statement: Authors declare no conflict of interests for this article.
Open-Access: This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution NonCommercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: https://creativecommons.org/Licenses/by-nc/4.0/
Corresponding author: Ahmed Elhariri, MD, Research Fellow, Division of Hematology-Oncology, Department of Medicine, Mayo Clinic Florida, Mayo Clinic Cancer Center, 4500 San Pablo Rd, Jacksonville, FL 32224, United States. Ahmed.Elhariri@bcm.edu
Received: April 12, 2023
Peer-review started: April 12, 2023
First decision: June 21, 2023
Revised: July 5, 2023
Accepted: July 27, 2023
Article in press: July 27, 2023
Published online: August 24, 2023
Abstract

Pancreatic cancer (PC) remains one of the most challenging diseases, with a very poor 5-year overall survival of around 11.5%. Kirsten rat sarcoma virus (KRAS) mutation is seen in 90%-95% of PC patients and plays an important role in cancer cell proliferation, differentiation, metabolism, and survival, making it an essential mutation for targeted therapy. Despite extensive efforts in studying this oncogene, there has been little success in finding a drug to target this pathway, labelling it for decades as “undruggable”. In this article we summarize some of the efforts made to target the KRAS pathway in PC, discuss the challenges, and shed light on promising clinical trials.

Keywords: Kirsten rat sarcoma virus, Targeted therapy, Pancreatic cancer, Drug resistance, Next generation sequencing, Clustered regularly interspaced short palindromic repeats

Core Tip: Kirsten rat sarcoma virus (KRAS) mutation is the hallmark of pancreatic cancer (PC) and an important therapeutic target. Approaches to target this oncogene has been challenging. We herein discuss the role of KRAS in development of PC, efforts made to target this pathway, and ongoing clinical trials.