Electrochemotherapy with bleomycin is effective in BRAF mutated melanoma cells and interacts with BRAF inhibitors.
BACKGROUND
The aim of the study was to explore the effectiveness of electrochemotherapy (ECT) during the treatment of melanoma patients with BRAF inhibitors. Its effectiveness was tested on BRAF mutated and non-mutated melanoma cells in vitro and in combination with BRAF inhibitors.


METHODS
ECT with bleomycin was performed on two human melanoma cell lines, with (SK-MEL-28) or without (CHL-1) BRAF V600E mutation. Cell survival was determined using clonogenic assay to determine the effectiveness of ECT in melanoma cells of different mutation status. Furthermore, the effectiveness of ECT in concomitant treatment with BRAF inhibitor vemurafenib was also determined in BRAF mutated cells SK-MEL-28 with clonogenic assay.


RESULTS
The survival of BRAF V600E mutated melanoma cells was even lower than non-mutated cells, indicating that ECT is effective regardless of the mutational status of melanoma cells. Furthermore, the synergistic interaction between vemurafenib and ECT with bleomycin was demonstrated in the BRAF V600E mutated melanoma cells.


CONCLUSIONS
The effectiveness of ECT in BRAF mutated melanoma cells as well as potentiation of its effectiveness during the treatment with vemurafenib in vitro implies on clinical applicability of ECT in melanoma patients with BRAF mutation and/or during the treatment with BRAF inhibitors.
Institute of Oncology Ljubljana, Ljubljana, Slovenia.
Tanja
T
Dolinsek
Institute of Oncology Ljubljana, Ljubljana, Slovenia.
Lara
L
Prosen
Institute of Oncology Ljubljana, Ljubljana, Slovenia; Faculty of Health Sciences, University of Primorska, Izola, Slovenia.
Maja
M
Cemazar
Institute of Oncology Ljubljana, Ljubljana, Slovenia.
Tjasa
T
Potocnik
Institute of Oncology Ljubljana, Ljubljana, Slovenia.
Gregor
G
Sersa
BRAF inhibitors; electrochemotherapy; melanoma; vemurafenib
Eur J Cancer. 2015 Jul;51(11):1435-43
25980594
Eur J Dermatol. 2015 May-Jun;25(3):271-2
26055291
J Neurooncol. 2016 Feb;126(3):385-93
26384810
Eur J Surg Oncol. 2013 Jan;39(1):4-16
22980492
Oncoimmunology. 2015 May 22;4(6):e1008842
26155423
N Engl J Med. 2012 Jun 28;366(26):2443-54
22658127
Nature. 2002 Jun 27;417(6892):949-54
12068308
Ann Oncol. 2015 Jun;26(6):1238-44
25762352
Eur J Surg Oncol. 2008 Feb;34(2):232-40
17614247
Oncoimmunology. 2014 Apr 15;3:e28131
25083316
Eur J Cancer. 2016 Jan;53:125-34
26707829
N Engl J Med. 2010 Aug 19;363(8):711-23
20525992
J Clin Oncol. 2013 May 10;31(14 ):1767-74
23569304
Eur J Cancer. 2015 Mar;51(5):642-52
25690538
N Engl J Med. 2011 Jun 30;364(26):2507-16
21639808
Lancet. 2012 Jul 28;380(9839):358-65
22735384
Cancer Immunol Immunother. 2015 Oct;64(10):1315-27
26067277
Am J Med. 1982 Jul 20;73(1A):36-9
6179416
Pharmacol Ther. 2014 May;142(2):176-82
24325952
Future Oncol. 2016 Jan;12(1):95-106
26616061
Radiol Oncol. 2015 Mar 03;49(1):71-4
25810704
Radiother Oncol. 2011 Mar;98 (3):394-9
21295875