PhD Scientific Days 2017

Oral Presentations: Oncology

Combination of pan-RAF and MEK inhibitionin nonV600E BRAF mutantcelllines

Előadó neve

Molnár, Eszter

Előadó munkahelye

2nd Departemnt of Pathology

Előadó telefonszáma

+36305907002

Előadó e-mail címe

m.molnareszter@gmail.com

Az előadás címe

Combination of pan-RAF and MEK inhibitionin nonV600E BRAF mutantcelllines

Szerző(k) neve és munkahelye

Eszter Molnár1, Tamás Garay1,2, Dominika Rittler1, Michael Grusch3, Walter Berger3, Balázs Döme4,5,6, József Tímár1,2, BalázsHegedűs 2,5,7
1 2nd Department of Pathology, Semmelweis University, Budapest, Hungary
2 HAS-SE Molecular Oncology Research Group, Budapest, Hungary
3 Institute of Cancer Research, Medical University of Vienna, Vienna, Austria
4 National Korányi Institute of TB and Pulmonology, Budapest, Hungary
5 Department of Thoracic Surgery, Medical University of Vienna, Vienna, Austria
6 Department of Thoracic Surgery, Semmelweis University, Budapest, Hungary
7 Department of Thoracic Surgery, Ruhrlandklinik, University Duisburg-Essen, Germany

Szekció

Oral Presentations: Oncology

Data of the presenter

Doctoral School of Pathological Sciences
Program: Oncology
Supervisor: Dr. Hegedűs Balázs
E-mail address: m.molnareszter@gmail.com

Text of the abstract

Background: Overall BRAF mutations are found in approximately 7% of all human cancers. The most common BRAF oncogenic mutation is V600E, however incidence of nonV600E BRAF mutation is not negligible in certain cancer types. Since there is no effective targeted therapy against nonV600E BRAF mutant tumors, we investigated the possibility of blocking oncogenic signaling of non V600E BRAF mutation by inhibiting two signaling elements in the MAPK pathway.
Methods: In vitro therapeutical effect of panRAF (sorafenib) and MEK (selumetinib) inhibition was assessed on six BRAF mutated human tumor cell lines A375 (V600E), CRL5885 (G466V), WM3629 (D594G), WM3670 (G469E), MDAMB231 (G464V), CRL5922 (L597V). Effect of inhibitors on proliferation, apoptosis induction, signal transduction and migration were investigated via SRB, TUNEL, immunoblot and videomicroscopy measurements, respectively. Both single agent and combination treatments were applied.
Results: Sorafenib and selumetinib combination treatment resulted in significant growth inhibition with synergism, increased induction of apoptosisand higher Erk activation inhibition when compared to single agent treatments. Combination treatment could also decrease migratory capacity in all the cell lines.
Conclusions: Our data suggests that combination blocking of RAF and MEKis sufficient toachieve effective therapeutic response in nonV600E BRAF mutant tumors.

Kind

Szabad

Előadás fájl jóváhagyás

nem rendelkezett róla

Előadó

1131

Authors (legacy)

Eszter Molnár1, Tamás Garay1,2, Dominika Rittler1, Michael Grusch3, Walter Berger3, Balázs Döme4,5,6, József Tímár1,2, BalázsHegedűs 2,5,7
1 2nd Department of Pathology, Semmelweis University, Budapest, Hungary
2 HAS-SE Molecular Oncology Research Group, Budapest, Hungary
3 Institute of Cancer Research, Medical University of Vienna, Vienna, Austria
4 National Korányi Institute of TB and Pulmonology, Budapest, Hungary
5 Department of Thoracic Surgery, Medical University of Vienna, Vienna, Austria
6 Department of Thoracic Surgery, Semmelweis University, Budapest, Hungary
7 Department of Thoracic Surgery, Ruhrlandklinik, University Duisburg-Essen, Germany