PTEN Status Alters the Molecular Route to Resistance to BRAF Inhibitor in Melanoma

Author Info

Qiang Zuo Yanlin Yu

Corresponding Author

Yanlin Yu
Laboratory of Cancer Biology and Genetics, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892- 4264, USA

A B S T R A C T

Although targeted treatment by BRAF inhibitors (BRAFi) achieved a remarkable clinical response for patients with BRAF mutation, the strength of efficacy is short and limited by acquired drug resistance [1]. Recent studies identified many mechanisms of acquired resistance to BRAFi, such as mutations in NRAS or MEK1 and overexpression of COT, EGFR, PDGFRβ, IGF1R or MET, lead the reactivation of MAPK pathway and drive the cell proliferation, suggesting that co-targeting this hyperactivated survival pathway by combination inhibitors might gain the maximum clinical benefits for melanoma patients. Based on these findings, FDA approved the combination of dabrafenib (BRAFi) with trametinib (MEK inhibitor) or vemurafenib (BRAFi) with cobimetinib (MEK inhibitor) to inhibit the MAPK signaling pathway in 2014 and 2015 more effectively. Indeed, the dual inhibitors of MEK and mutant BRAF kinases have shown a higher overall survival rate and exciting results in initial tumor response in clinical. Moreover, this combinational treatment can prevent or delays the acquired resistance. However, the benefit of the combination did not last too long due to anew therapy resistance, which continues to obstacle the clinical applications. Novel strategies and molecular mechanism are therefore needed to improve the precision and efficiency of targeted therapy for resistant melanoma

Article Info

Article Type

Research Article

Publication history

Received: Thu 22, Aug 2019
Accepted: Tue 10, Sep 2019
Published: Mon 23, Sep 2019

Copyright

© 2023 Yanlin Yu. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Hosting by Science Repository.
DOI: 10.31487/j.COR.2019.04.06