Targeting Medulloblastoma
Purpose
To communicate the method of action and downfalls of Vismodegib, a targeted therapy previously used to treat Medulloblastoma.
Client
Derek Ng
Date
July 2021
Medium
Infographic
Tools
Maya, VMD, Photoshop, Procreate, Illustrator
Primary Audience
Educated lay
Rough Sketches
The project began with several rough concept sketches for different topics within the realm of Medulloblastoma and the sonic hedgehog signaling pathway.
Comprehensive Sketch
A final comprehensive sketch was created after receiving feedback from peers, prior to creating the final illustrations.
References
An, X., Bai, Q., Bai, F., Shi, D., Liu, H., & Yao, X. (2019). Deciphering the allosteric effect of antagonist vismodegib on smoothened receptor deactivation using metadynamics simulation. Frontiers in Chemistry, 7(406). https://doi.org/10.3389/fchem.2019.0040
Briscoe, J., & Thérond, P. P. (2013). The mechanisms of Hedgehog signalling and its roles in development and disease. Nature Reviews Molecular Cell Biology, 14(7), 418–431. https://doi.org/10.1038/nrm3598
Byrne, E. F. X., Luchetti, G., Rohatgi, R., & Siebold, C. (2018). Multiple ligand binding sites regulate the Hedgehog signal transducer Smoothened in vertebrates. Current Opinion in Cell Biology, 51, 81–88. https://doi.org/10.1016/j.ceb.2017.10.004
Byrne, E. F. X., Sircar, R., Miller, P. S., Hedger, G., Luchetti, G., Nachtergaele, S., Tully, M. D., Mydock-Mcgrane, L., Covey, D. F., Rambo, R. P., Sansom, M. S. P., Newstead, S., Rohatgi, R., & Siebold, C. (2016). Structural basis of Smoothened regulation by its extracellular domains. Nature, 535(7613), 517–522. https://doi.org/10.1038/nature18934
De Souza E Cassia, G., Alves, C. A. P. F., Taranath, A., López, N. S., Oztekin, O., Gonçalves, F. G., & Patay, Z. (2018). Childhood medulloblastoma revisited. Topics in Magnetic Resonance Imaging, 27(6), 479–502. https://doi.org/10.1097/RMR.0000000000000184
Gould, S. E., Low, J. A., Marsters, J. C., Robarge, K., Rubin, L. L., De Sauvage, F. J., Sutherlin, D. P., Wong, H., & Yauch, R. L. (2014). Discovery and preclinical development of vismodegib. Expert Opinion on Drug Discovery, 9(8), 969–984. https://doi.org/10.1517/17460441.2014.920816
Huang, P., Zheng, S., Wierbowski, B. M., Kim, Y., Nedelcu, D., Aravena, L., Liu, J., Kruse, A. C., & Salic, A. (2018). Structural Basis of Smoothened Activation in Hedgehog Signaling. Cell, 174(2), 312-324.e16. https://doi.org/10.1016/j.cell.2018.04.029
Lospinoso Severini, L., Ghirga, F., Bufalieri, F., Quaglio, D., Infante, P., & Di Marcotullio, L. (2020). The SHH/GLI signaling pathway: a therapeutic target for medulloblastoma. Expert Opinion on Therapeutic Targets, 24(11). https://doi.org/10.1080/14728222.2020.1823967
Northcott, P. A., Robinson, G. W., Kratz, C. P., Mabbott, D. J., Pomeroy, S. L., Clifford, S. C., Rutkowski, S., Ellison, D. W., Malkin, D., Taylor, M. D., Gajjar, A., & Pfister, S. M. (2019). Medulloblastoma. Nature Reviews Disease Primers, 5(1). https://doi.org/10.1038/s41572-019-0063-6
Royden Jones, H., Burns, T. M., Aminoff, M. J., & Pomeroy, S. L. (2013). The Netter Collection of Medical Illustrations: Nervous System (2nd ed., Vol. 7). Elsevier Inc.
Sommer, A., & Lemmon, M. A. (2018). Smoothening out the patches: New roles are discovered for cholesterol transport in a key developmental signaling pathway. Science, 362(6410), 26–27. https://doi.org/10.1126/science.aav1025
PDBs: 6D32, 5L71, 6E1H