@article{7f171142d25c449dad7e53242c8c1304,
title = "Enhancing the evaluation of PI3K inhibitors through 3D melanoma models",
abstract = "Targeted therapies for mutant BRAF metastatic melanoma are effective but not curative due to acquisition of resistance. PI3K signaling is a common mediator of therapy resistance in melanoma; thus, the need for effective PI3K inhibitors is critical. However, testing PI3K inhibitors in adherent cultures is not always reflective of their potential in vivo. To emphasize this, we compared PI3K inhibitors of different specificity in two- and three-dimensional (2D, 3D) melanoma models and show that drug response predictions gain from evaluation using 3D models. Our results in 3D demonstrate the anti-invasive potential of PI3K inhibitors and that drugs such as PX-866 have beneficial activity in physiological models alone and when combined with BRAF inhibition. These assays finally help highlight pathway effectors that could be involved in drug response in different environments (e.g. p4E-BP1). Our findings show the advantages of 3D melanoma models to enhance our understanding of PI3K inhibitors.",
keywords = "3D models, Melanoma, Mutant BRAF, PI3K inhibition, PX-866, Resistance",
author = "Batool Shannan and Quan Chen and Andrea Watters and Michela Perego and Clemens Krepler and Rakhee Thombre and Ling Li and Geena Rajan and Scott Peterson and Gimotty, {Phyllis A.} and Melissa Wilson and Nathanson, {Katherine L.} and Gangadhar, {Tara C.} and Schuchter, {Lynn M.} and Weeraratna, {Ashani T.} and Meenhard Herlyn and Adina Vultur",
note = "Funding Information: We thank Oncothyreon for PX866, and G. Bollag (Plexxikon) for PLX4720. We also thank F. Kenney and J. Hayden of the Wistar Imaging Facility, R. Delgiacco of the Wistar Histology Facility, D. Schultz of the Molecular Screening Facility, Jeffrey Faust of the Flow Cytometry Facility, and Qin Liu, Xiangfan Yin for biostatistics. AV, KLN, and MH are members of the ITMAT-University of Pennsylvania. This work was supported by NIH grants PO1 CA114046, P01 CA025874, R01 CA047159, P50 CA 174523, CA 076674, and by the Dr. Miriam and Sheldon G. Adelson Medical Research Foundation. Funding Information: We thank Oncothyreon for PX866, and G. Bollag (Plexxikon) for PLX4720. We also thank F. Kenney and J. Hayden of the Wistar Imaging Facility, R. Delgiacco of the Wistar Histology Facility, D. Schultz of the Molecular Screening Facility, Jeffrey Faust of the Flow Cytometry Facility, and Qin Liu, Xiangfan Yin for biostatistics. AV, KLN, and MH are members of the ITMAT-University of Pennsylvania. This work was supported by NIH grants PO1 CA114046, P01 CA025874, R01 CA047159, P50 CA 174523, CA 076674, and by the Dr. Miriam and Sheldon G. Adelson Medical Research Foundation. Publisher Copyright: {\textcopyright} 2016 John Wiley & Sons A/S.",
year = "2016",
month = may,
day = "1",
doi = "10.1111/pcmr.12465",
language = "English (US)",
volume = "29",
pages = "317--328",
journal = "Pigment Cell and Melanoma Research",
issn = "1755-1471",
publisher = "Wiley-Blackwell",
number = "3",
}