XL888 Limits Vemurafenib-Induced Proliferative Skin Events by Suppressing Paradoxical MAPK Activation - PubMed (original) (raw)

XL888 Limits Vemurafenib-Induced Proliferative Skin Events by Suppressing Paradoxical MAPK Activation

Manali Phadke et al. J Invest Dermatol. 2015 Oct.

No abstract available

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Conflict of interest statement

Conflicts of interest

G. Gibney has served as a consultant for BMS, Genentech and Novartis. V. Sondak has served as a consultant for Merck, OncoSec, MabVax, Polynoma and Genentech. J. Weber has received honoraria from Genentech and GSK. All other authors declare no conflict of interest.

Figures

Figure 1

Figure 1. Incidence of secondary skin lesions by dose cohort of XL888

Chart shows the incidence of hyperproliferative/neoplastic skin lesions (melanoma, SCC: squamous cell carcinoma, KA: keratoacanthoma, and VV: verucca vulgaris, stratified by XL888 dose cohort (cohort 1: 30mg; cohort 2: 45mg; cohort 3: 90mg; cohort 4: 135mg). Data shows number of lesions of each type for each individual patient. Cohort had 7 total events (3/3 patients), cohort 2 had 6 total events (2/3 patients), cohort 3 had 3 total events (2/3 patients) and cohort 4 had 3 total events (2/6 patients).

Figure 2

Figure 2. XL888 suppresses paradoxical MAPK signaling in _NRAS_-mutant melanoma and _HRAS_-transformed NIH3T3 cells

a: XL888 prevents the paradoxical MAPK signaling in 3 NRAS mutant melanoma cell lines. IPC-298, M245 and WM1366 cell lines were treated with vemurafenib (1 μM, 72 hrs) in the absence and presence of XL888 (300 nM). Western blots show total CRAF, phospho-ERK and total ERK. b: XL888 (300 nM) suppressed vemurafenib-driven (1 μM, 72 hrs) paradoxical MAPK signaling in NIH3T3 cells transduced with HRAS Q61L.

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