Beyond the Genomic Mutation: Rethinking the Molecular Biomarkers of K-RAS Dependency in Pancreatic Cancers
1
Department of Research, Advanced Diagnostics and Technological Innovations, IRCCS Regina Elena National Cancer Institute, 00144 Rome, Italy
2
Institute of Biochemistry and Cellular Biology, CNR National Research Council, 00015 Rome, Italy
*
Author to whom correspondence should be addressed.
Int. J. Mol. Sci. 2020, 21(14), 5023; https://doi.org/10.3390/ijms21145023
Received: 15 June 2020
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Revised: 13 July 2020
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Accepted: 14 July 2020
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Published: 16 July 2020
(This article belongs to the Special Issue New Prognostic and Predictive Markers in Cancer Progression)
Oncogenic v-Ki-ras2 Kirsten rat sarcoma viral oncogene homolog (K-RAS) plays a key role in the development and maintenance of pancreatic ductal adenocarcinoma (PDAC). The targeting of K-RAS would be beneficial to treat tumors whose growth depends on active K-RAS. The analysis of K-RAS genomic mutations is a clinical routine; however, an emerging question is whether the mutational status is able to identify tumors effectively dependent on K-RAS for tailoring targeted therapies. With the emergence of novel K-RAS inhibitors in clinical settings, this question is relevant. Several studies support the notion that the K-RAS mutation is not a sufficient biomarker deciphering the effective dependency of the tumor. Transcriptomic and metabolomic profiles of tumors, while revealing K-RAS signaling complexity and K-RAS-driven molecular pathways crucial for PDAC growth, are opening the opportunity to specifically identify K-RAS-dependent- or K-RAS-independent tumor subtypes by using novel molecular biomarkers. This would help tumor selection aimed at tailoring therapies against K-RAS. In this review, we will present studies about how the K-RAS mutation can also be interpreted in a state of K-RAS dependency, for which it is possible to identify specific K-RAS-driven molecular biomarkers in certain PDAC subtypes, beyond the genomic K-RAS mutational status.
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Keywords:
pancreatic cancer; K-RAS oncogene; oncogene dependency; targeted therapies; biomarkers; genomic mutations; transcriptomics; metabolomics
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MDPI and ACS Style
Mottini, C.; Cardone, L. Beyond the Genomic Mutation: Rethinking the Molecular Biomarkers of K-RAS Dependency in Pancreatic Cancers. Int. J. Mol. Sci. 2020, 21, 5023. https://doi.org/10.3390/ijms21145023
AMA Style
Mottini C, Cardone L. Beyond the Genomic Mutation: Rethinking the Molecular Biomarkers of K-RAS Dependency in Pancreatic Cancers. International Journal of Molecular Sciences. 2020; 21(14):5023. https://doi.org/10.3390/ijms21145023
Chicago/Turabian StyleMottini, Carla, and Luca Cardone. 2020. "Beyond the Genomic Mutation: Rethinking the Molecular Biomarkers of K-RAS Dependency in Pancreatic Cancers" International Journal of Molecular Sciences 21, no. 14: 5023. https://doi.org/10.3390/ijms21145023
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