Adaptive responses as mechanisms of resistance to braf inhibitors in melanoma
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The introduction of v-raf murine sarcoma viral oncogene homolog B (BRAF) inhibitors in melanoma patients with BRAF (V600E) mutations has demonstrated significant clinical benefits. However, rarely do tumours regress completely. Frequently, the reason for this is that therapies targeting specific oncogenic mutations induce a number of intrinsic compensatory mechanisms, also known as adaptive responses or feedback loops, that enhance the pro-survival and pro-proliferative capacity of a proportion of the original tumour population, thereby resulting in tumour progression. In this review we will summarize the known adaptive responses that limit BRAF mutant therapy and discuss potential novel combinatorial therapies to overcome resistance.
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Saei, A.; Palafox, M.; Benoukraf, T.; Kumari, N.; Jaynes, P.; Iyengar, P.; Muñoz Couselo, E.; Nuciforo, P.; Cortés, J.; Nötzel, C.; Kumarakulasinghe, N.; Richard, J.; Isa, Z.; Pang, B.; Guzman, M.; Siqin, Z.; Yang, H.; Tam, W.; Serra, V.; Eichhorn, Pieter (2018)© 2018 Saei et al. RAF kinase inhibitors are clinically active in patients with BRAF (V600E) mutant melanoma. However, rarely do tumors regress completely, with the majority of responses being short-lived. This is partially ...
Saei, A.; Eichhorn, Pieter (2018)© 2018, © 2018 The Author(s). Published by Taylor & Francis. Response to targeted therapies is limited by the activation or inhibition of feedback loops. Here we report the ubiquitin specific peptidase 28/F-box WD ...
Physiological characteristics associated with increased resistance to decompression sickness in male and female rats.Lautridou, Jacky; Dugrenot, Emmanuel; Amérand, Aline; Guernec, Anthony; Pichavant-Rafini, Karine; Goanvec, Christelle; Inizan, Manon; Albacete, Gaelle; Belhomme, Marc; Galinat, Hubert; Lafère, Pierre; Balestra, Costantino; Moisan, Christine; Buzzacott, Peter ; Guerrero, François (2020)Decompression sickness (DCS) is a complex and poorly understood systemic disease with wide inter-individual resistance variability. We selectively bred rats with a 3-fold greater resistance to DCS than standard ones. To ...