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Targeting KRAS in pancreatic cancer

SANDRA STICKLER, BARBARA RATH, GERHARD HAMILTON*

Institute of Pharmacology, Medical University of Vienna, Vienna, A-1090, Austria

* Corresponding Author: GERHARD HAMILTON. Email: email

(This article belongs to the Special Issue: Recent Advances in Cancer Pharmacology)

Oncology Research 2024, 32(5), 799-805. https://doi.org/10.32604/or.2024.045356

Abstract

Pancreatic cancer has a dismal prognosis due to late detection and lack of efficient therapies. The Kirsten rat sarcoma virus (KRAS) oncogene is mutated in up to 90% of all pancreatic ductal adenocarcinomas (PDACs) and constitutes an attractive target for therapy. However, the most common KRAS mutations in PDAC are G12D (44%), G12V (34%) and G12R (20%) that are not amenable to treatment by KRAS G12C-directed cysteine-reactive KRAS inhibitors such as Sotorasib and Adagrasib that exhibit clinical efficacy in lung cancer. KRAS G12C mutant pancreatic cancer has been treated with Sotorasib but this mutation is detected only in 2%–3% of PDAC. Recently, the KRAS G12D-directed MRTX1133 inhibitor has entered clinical trials and more of such inhibitors are in development. The other KRAS mutations may be targeted indirectly via inhibition of the cognate guanosine exchange factor (GEF) Son of Sevenless 1 that drives KRAS. These agents seem to provide the means to target the most frequent KRAS mutations in PDAC and to improve patient outcomes.

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APA Style
STICKLER, S., RATH, B., HAMILTON, G. (2024). Targeting KRAS in pancreatic cancer. Oncology Research, 32(5), 799-805. https://doi.org/10.32604/or.2024.045356
Vancouver Style
STICKLER S, RATH B, HAMILTON G. Targeting KRAS in pancreatic cancer. Oncol Res. 2024;32(5):799-805 https://doi.org/10.32604/or.2024.045356
IEEE Style
S. STICKLER, B. RATH, and G. HAMILTON "Targeting KRAS in pancreatic cancer," Oncol. Res., vol. 32, no. 5, pp. 799-805. 2024. https://doi.org/10.32604/or.2024.045356



cc This work is licensed under a Creative Commons Attribution 4.0 International License , which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
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