Metastatic melanoma cells with BRAF G469A mutation: Nab-paclitaxel better than vemurafenib?

Research output: Contribution to journalArticlepeer-review

Abstract

Purpose: BRAF G469A is a missense mutation within exon 11 of the BRAF gene resulting in a constitutively activated enzyme frequently associated with MAP kinase cascade signaling activation. No evidence currently exists about its role in determining sensitivity/resistance to BRAF inhibitors, utilized in the treatment of patients carrying BRAF V600 mutations, and to chemotherapy. The newly established metastatic melanoma (MM) cell line MO-1 was characterized for its sensitivity to vemurafenib and nab-paclitaxel, both already utilized for the treatment of MM. Methods: All analyses were carried out by comparing results with those found in MM cells wild type for BRAF or mutated in V600. In addition, cellular effectors were investigated by ELISA kits, western blotting and flow cytometry. Results: The exposure to vemurafenib inhibited MO-1 cell proliferation at concentrations similar to those obtained in vemurafenib-resistant melanoma models, and an explanation of this sensitivity is the strong activation of Erk1/2 and the low expression of MITF. Nab-paclitaxel strongly reduced proliferation of MO-1 cells perhaps for the very low expression level of PMEL17, transcriptionally regulated by MITF and negatively involved in determining sensitivity to taxanes. Conclusions: Thus, the mutation BRAF G469A in MM might be related to a weak effectiveness of therapy with BRAF inhibitors and a promising therapeutic approach may be with nab-paclitaxel.

Original languageEnglish
Pages (from-to)433-438
Number of pages6
JournalCancer Chemotherapy and Pharmacology
Volume76
Issue number2
DOIs
Publication statusPublished - Jun 13 2015

Keywords

  • BRAF G469A mutation
  • Metastatic melanoma
  • Nab-paclitaxel
  • PMEL17
  • Vemurafenib

ASJC Scopus subject areas

  • Cancer Research
  • Oncology
  • Pharmacology
  • Pharmacology (medical)
  • Toxicology
  • Medicine(all)

Fingerprint Dive into the research topics of 'Metastatic melanoma cells with BRAF G469A mutation: Nab-paclitaxel better than vemurafenib?'. Together they form a unique fingerprint.

Cite this