Malak Sabbah
Current Organizations / Institutes
The organizations/institutes from the scholar's latest article
Research Subjects
Research Interests
Malak Sabbah has a total of 18 co-authors. Here are the top co-authors by number of shared publications:
- Ghanem Ghanem
Laboratory of Oncology and Experimental Surgery, Institut Jules Bordet, Université Libre de Bruxelles, 1000 Brussels, Belgium
2 shared publications - Ahmad Awada
Laboratory of Oncology and Experimental Surgery, Institut Jules Bordet, Université Libre de Bruxelles, 1000 Brussels, Belgium
1 shared publication - Ahmad Najem
Laboratory of Oncology and Experimental Surgery, Institut Jules Bordet, Université Libre de Bruxelles, 1000 Brussels, Belgium
1 shared publication - An Wouters
University of Antwerp
1 shared publication - Coralie Reger de Moura
INSERM, U976, Team 1, Human Immunology Pathophysiology & Immunotherapy (HIPI), F-75010 Paris, France
1 shared publication - Céleste Lebbé
Université Paris Cite, AP-HP Dermato-oncology and CIC, Cancer Institute APHP.nord Paris cité, INSERM U1342—Equipe—CNRS EMR8000, Saint Louis Hospital, Paris, France
1 shared publication
Latest Publications
- Open Access
FGF2 Induces Resistance to Nilotinib through MAPK Pathway Activation in KIT Mutated Melanoma
KIT is a bona fide oncogene in a subset of melanoma and, ex vivo, KIT inhibitors are very efficient at killing KIT-mutant melanoma cell lines. However, KIT-mutant melanoma tumors tend to show a de novo resistance in most cases and a limited duration of response when response is achieved. We performed pharmacodynamic studies on patients with KIT-mutated melanoma treated with nilotinib, which suggested that the FGF2 axis may be a mechanism of resistance in this subset of melanoma. Using several melanoma cell lines, which are dependent on oncogenic KIT, we showed that although KIT inhibition markedly decreased cell viability in melanoma cell lines with distinct KIT mutations, this effect was lessened in the presence of FGF2 due to inhibition of BIM expression by MAPK pathway activation. Addition of a MEK inhibitor reversed the FGF2-driven resistance for all KIT mutants. We confirmed the expression of FGF2 and activation of MEK-ERK in melanoma patients using in situ data from a clinical trial. Therefore, the combined inhibition of KIT with FGFR or MEK may be a next-step effective clinical strategy in KIT-mutant melanoma.
Open AccessFGF2 Induces Resistance to Nilotinib through MAPK Pathway Activation in KIT Mutated Melanoma
KIT is a bona fide oncogene in a subset of melanoma and, ex vivo, KIT inhibitors are very efficient at killing KIT-mutant melanoma cell lines. However, KIT-mutant melanoma tumors tend to show a de novo resistance in most cases and a limited duration of response when response is achieved. We performed pharmacodynamic studies on patients with KIT-mutated melanoma treated with nilotinib, which suggested that the FGF2 axis may be a mechanism of resistance in this subset of melanoma. Using several melanoma cell lines, which are dependent on oncogenic KIT, we showed that although KIT inhibition markedly decreased cell viability in melanoma cell lines with distinct KIT mutations, this effect was lessened in the presence of FGF2 due to inhibition of BIM expression by MAPK pathway activation. Addition of a MEK inhibitor reversed the FGF2-driven resistance for all KIT mutants. We confirmed the expression of FGF2 and activation of MEK-ERK in melanoma patients using in situ data from a clinical trial. Therefore, the combined inhibition of KIT with FGFR or MEK may be a next-step effective clinical strategy in KIT-mutant melanoma.