Academic Journal
The benefit of co-targeting PARP-1 and c-Met on the efficacy of radiotherapy in wild type BRAF melanoma.
| العنوان: | The benefit of co-targeting PARP-1 and c-Met on the efficacy of radiotherapy in wild type BRAF melanoma. |
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| المؤلفون: | Sabbah, Malak, Najem, Ahmad, Vanderkerkhove, Christophe, Kert, Fabien, Jourani, Younes, Journe, Fabrice, Awada, Ahmad, Van Gestel, Dirk, Ghanem, Ghanem E, Krayem, Mohammad |
| المساهمون: | M112 - Anatomie humaine et Oncologie expérimentale, R550 - Institut des Sciences et Technologies de la Santé |
| المصدر: | Frontiers in Medicine, 10, 1149918 (2023) |
| بيانات النشر: | Frontiers Media SA |
| سنة النشر: | 2023 |
| مصطلحات موضوعية: | PARP inhibition, RTK inhibition, WTBRAF, melanoma, radiotherapy, Medicine (all), General Medicine, Human health sciences, Oncology, Sciences de la santé humaine, Oncologie |
| الوصف: | peer reviewed ; Melanoma is known to be a radioresistant cancer. Melanoma radioresistance can be due to several factors such as pigmentation, antioxidant defenses and high Deoxyribonucleic acid (DNA) repair efficacy. However, irradiation induces intracellular translocation of RTKs, including cMet, which regulates response to DNA damage activating proteins and promotes DNA repair. Accordingly, we hypothesized that co-targeting DNA repair (PARP-1) and relevant activated RTKs, c-Met in particular, may radiosensitize wild-type B-Raf Proto-Oncogene, Serine/Threonine Kinase (WTBRAF) melanomas where RTKs are often upregulated. Firstly, we found that PARP-1 is highly expressed in melanoma cell lines. PARP-1 inhibition by Olaparib or its KO mediates melanoma cell sensitivity to radiotherapy (RT). Similarly, specific inhibition of c-Met by Crizotinib or its KO radiosensitizes the melanoma cell lines. Mechanistically, we show that RT causes c-Met nuclear translocation to interact with PARP-1 promoting its activity. This can be reversed by c-Met inhibition. Accordingly, RT associated with the inhibition of both c-Met and PARP-1 resulted in a synergistic effect not only on tumor growth inhibition but also on tumor regrowth control in all animals following the stop of the treatment. We thus show that combining PARP and c-Met inhibition with RT appears a promising therapeutic approach in WTBRAF melanoma. |
| نوع الوثيقة: | article in journal/newspaper |
| اللغة: | English |
| تدمد: | 2296-858X |
| Relation: | https://www.frontiersin.org/articles/10.3389/fmed.2023.1149918/full; urn:issn:2296-858X; https://orbi.umons.ac.be/handle/20.500.12907/48128; info:hdl:20.500.12907/48128; info:pmid:37215708 |
| DOI: | 10.3389/fmed.2023.1149918 |
| الاتاحة: | https://orbi.umons.ac.be/handle/20.500.12907/48128 https://hdl.handle.net/20.500.12907/48128 https://orbi.umons.ac.be/bitstream/20.500.12907/48128/1/fmed-10-1149918.pdf https://doi.org/10.3389/fmed.2023.1149918 |
| Rights: | open access ; http://purl.org/coar/access_right/c_abf2 ; info:eu-repo/semantics/openAccess |
| رقم الانضمام: | edsbas.1F0CEA09 |
| قاعدة البيانات: | BASE |
Full Text Finder | تدمد: | 2296858X |
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| DOI: | 10.3389/fmed.2023.1149918 |