Wild-type KRAS is a novel therapeutic target for melanoma contributing to primary and acquired resistance to BRAF inhibition

Dietrich P, Kuphal S, Spruss T, Hellerbrand C, Boßerhoff AK (2017)

Publication Type: Journal article

Publication year: 2017

Journal

Oncogene Springer Nature

DOI: 10.1038/onc.2017.391

Abstract

Malignant melanoma reveals rapidly increasing incidence and mortality rates worldwide. By now, BRAF inhibition is the standard therapy for advanced melanoma in patients carrying BRAF mutations. However, only approximately 50% of melanoma patients harbor therapeutically attackable BRAF mutations, and overall survival after treatment with BRAF inhibitors is modest. KRAS (Kirsten Rat sarcoma) proteins are acting upstream of BRAF and have a major role in human cancer. Recent approaches awaken the hope to use KRAS inhibition (KRASi) as a clinical tool. In this study, we identified wild-type KRAS as a novel therapeutic target in melanoma. KRASi functions synergistically with BRAF inhibition to reduce melanoma proliferation and to induce apoptosis independently of BRAF mutational status. Moreover, acquired resistance to BRAF inhibitors in melanoma is dependent on dynamic regulation of KRAS expression with subsequent AKT and extracellular-signal regulated kinase activation and can be overcome by KRASi. This suggests KRASi as novel approach in melanoma-alone or in combination with other therapeutic regimes.Oncogene advance online publication, 23 October 2017; doi:10.1038/onc.2017.391.

Authors with CRIS profile

Peter Dietrich Lehrstuhl für Biochemie und Molekulare Medizin Silke Kuphal Lehrstuhl für Biochemie und Molekulare Medizin Claus Hellerbrand Professur für Biochemie und Molekulare Pathobiologie Anja Katrin Boßerhoff Lehrstuhl für Biochemie und Molekulare Medizin

Additional Organisation(s)

Interdisziplinäres Zentrum für Klinische Forschung

Involved external institutions

Universität Regensburg DE Germany (DE)

How to cite

APA:

Dietrich, P., Kuphal, S., Spruss, T., Hellerbrand, C., & Boßerhoff, A.K. (2017). Wild-type KRAS is a novel therapeutic target for melanoma contributing to primary and acquired resistance to BRAF inhibition. Oncogene. https://doi.org/10.1038/onc.2017.391

MLA:

Dietrich, Peter, et al. "Wild-type KRAS is a novel therapeutic target for melanoma contributing to primary and acquired resistance to BRAF inhibition." Oncogene (2017).

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