Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Review
. 2022 Nov 8;12(11):1870.
doi: 10.3390/jpm12111870.

Targeting KRAS in Pancreatic Cancer

Darren Cowzer  1 , Mohammed Zameer  1 , Michael Conroy  1 , Walter Kolch  2   3 , Austin G Duffy  1
Affiliations
Review

Targeting KRAS in Pancreatic Cancer

Darren Cowzer et al. J Pers Med. .

Abstract

Pancreatic cancer is mainly driven by mutations in the KRAS oncogene. While this cancer has shown remarkable therapy resistance, new approaches to inhibit mutated KRAS, KRAS activators and effectors show promise in breaking this therapeutic deadlock. Here, we review these innovations in therapies that target RAS signaling in pancreatic cancer from a clinical point of view. A number of promising approaches are currently in clinical trials or in clinical development. We focus on small-molecule drugs but also discuss immunotherapies and tumor vaccines.

Keywords: KRAS; pancreas cancer; targeted therapy.

PubMed Disclaimer

Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1
Figure 1
Intracellular targeting of RAS. Created with Biorender.com (accessed on 30 October 2022).
See this image and copyright information in PMC

References

    1. Conroy T., Desseigne F., Ychou M., Bouche O., Guimbaud R., Becouarn Y., Adenis A., Raoul J.L., Gourgou-Bourgade S., de la Fouchardiere C., et al. FOLFIRINOX versus gemcitabine for metastatic pancreatic cancer. N. Engl. J. Med. 2011;364:1817–1825. doi: 10.1056/NEJMoa1011923. - DOI - PubMed
    1. Mukhopadhyay S., Vander Heiden M.G., McCormick F. The Metabolic Landscape of RAS-Driven Cancers from biology to therapy. Nat. Cancer. 2021;2:271–283. doi: 10.1038/s43018-021-00184-x. - DOI - PMC - PubMed
    1. Moore A.R., Rosenberg S.C., McCormick F., Malek S. RAS-targeted therapies: Is the undruggable drugged? Nat. Rev. Drug Discov. 2020;19:533–552. doi: 10.1038/s41573-020-0068-6. - DOI - PMC - PubMed
    1. Punekar S.R., Velcheti V., Neel B.G., Wong K.K. The current state of the art and future trends in RAS-targeted cancer therapies. Nat. Rev. Clin. Oncol. 2022;19:637–655. doi: 10.1038/s41571-022-00671-9. - DOI - PMC - PubMed
    1. Hamarsheh S., Groß O., Brummer T., Zeiser R. Immune modulatory effects of oncogenic KRAS in cancer. Nat. Commun. 2020;11:5439. doi: 10.1038/s41467-020-19288-6. - DOI - PMC - PubMed

LinkOut - more resources