| Title |
Targeting Anaplastic Lymphoma Kinase (ALK) in Rhabdomyosarcoma (RMS) with the Second-Generation ALK Inhibitor Ceritinib
|
|---|---|
| Published in |
Targeted Oncology, October 2017
|
| DOI | 10.1007/s11523-017-0528-z |
| Pubmed ID | |
| Authors |
Anke E. M. van Erp, Melissa H. S. Hillebrandt-Roeffen, Laurens van Houdt, Emmy D. G. Fleuren, Winette T. A. van der Graaf, Yvonne M. H. Versleijen-Jonkers |
| Abstract |
The receptor tyrosine kinase (RTK) anaplastic lymphoma kinase (ALK) has been implicated in the tumorigenesis of rhabdomyosarcoma (RMS). However, the exact role of ALK in RMS is debatable and remains to be elucidated. To determine the in vitro and in vivo effects and mechanism of action of the second-generation ALK inhibitor ceritinib on RMS cell growth. Effects of ceritinib on cell proliferation, wound healing, cell cycle, and RTK signaling were determined in alveolar and embryonal rhabdomyosarcoma (ARMS, ERMS). In addition, possible synergistic effects of combined treatment with ceritinib and the Abl/Src family kinase inhibitor dasatinib were determined. Ceritinib treatment led to decreased cell proliferation, cell cycle arrest, apoptosis, and decreased in vivo tumor growth for the ARMS subtype. ERMS cell lines were less affected and showed no cell cycle arrest or apoptosis. Both subtypes lacked intrinsic ALK phosphorylation, and ceritinib was shown to affect the IGF1R signaling pathway. High levels of phosphorylated Src (Tyr416) were present following ceritinib treatment, making combined treatment with a Src inhibitor a potential treatment option. Combined treatment of ceritinib and dasatinib showed synergistic effects in both ERMS and ARMS cell lines. This study shows that monotherapy with an ALK inhibitor, such as ceritinib, in RMS, has no effect on ALK signaling. However, the synergistic effects of ceritinib and dasatinib are promising, most probably due to targeting of IGF1R and Src. |
X Demographics
The data shown below were collected from the profile of 1 X user who shared this research output. Click here to find out more about how the information was compiled.
Geographical breakdown
| Country | Count | As % |
|---|---|---|
| Unknown | 1 | 100% |
Demographic breakdown
| Type | Count | As % |
|---|---|---|
| Science communicators (journalists, bloggers, editors) | 1 | 100% |
Mendeley readers
The data shown below were compiled from readership statistics for 39 Mendeley readers of this research output. Click here to see the associated Mendeley record.
Geographical breakdown
| Country | Count | As % |
|---|---|---|
| Unknown | 39 | 100% |
Demographic breakdown
| Readers by professional status | Count | As % |
|---|---|---|
| Researcher | 7 | 18% |
| Student > Ph. D. Student | 5 | 13% |
| Student > Bachelor | 4 | 10% |
| Student > Doctoral Student | 3 | 8% |
| Professor | 3 | 8% |
| Other | 8 | 21% |
| Unknown | 9 | 23% |
| Readers by discipline | Count | As % |
|---|---|---|
| Medicine and Dentistry | 9 | 23% |
| Biochemistry, Genetics and Molecular Biology | 8 | 21% |
| Pharmacology, Toxicology and Pharmaceutical Science | 3 | 8% |
| Chemistry | 3 | 8% |
| Nursing and Health Professions | 1 | 3% |
| Other | 4 | 10% |
| Unknown | 11 | 28% |
Attention Score in Context
This research output has an Altmetric Attention Score of 1. This is our high-level measure of the quality and quantity of online attention that it has received. This Attention Score, as well as the ranking and number of research outputs shown below, was calculated when the research output was last mentioned on 25 October 2017.
All research outputs
#18,574,814
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Outputs from Targeted Oncology
#395
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Outputs of similar age from Targeted Oncology
#9
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