Yael Mossé Laboratory

Led by Yael P. Mossé, MD, a pediatric oncologist committed to advancing therapies based on research, researchers in the Mossé Laboratory are studying the contribution of DNA sequence variations and activation mutations of anaplastic lymphoma kinase (ALK) genes on the development and progression of both inherited and acquired forms of neuroblastoma. The goal of the research conducted in this laboratory is to understand the underlying molecular mechanisms by which ALK gene activation contributes to development and progression of pediatric neuroblastoma, and to identify less toxic, more targeted cancer therapies to treat children with ALK-mediated disease.

New Drug May Overcome Treatment Resistance in a High-risk Children’s Cancer

Selected Publications

Dual ALK and CDK4/6 inhibition demonstrates on-target synergy against neuroblastoma. Clin Cancer Res. 2016 Dec 16.
Wood A, Krytska K, Ryles HT, Infarinato NR, Sano R, Hansel TD, Hart LS, King F, Smith TR, Ainscow E, Grandinetti KB, Tuntland T, Kim S, Caponigro G, He YQ, Krupa S, Li N, Harris J, Mosse YP.


Phase I study of the aurora a kinase inhibitor alisertib in combination with irinotecan and temozolomide for patients with relapsed or refractory neuroblastoma: A NANT (new approaches to neuroblastoma therapy) Trial. J Clin Oncol. 2016 Feb 16. pii: JCO654889. [Epub ahead of print].
DuBois SG, Marachelian A, Fox E, Kudgus RA, Reid JM, Groshen S, Malvar J, Bagatell R, Wagner L, Maris JM, Hawkins R, Courtier J, Lai H, Goodarzian F, Shimada H, Czarnecki S, Tsao-Wei D, Matthay KK, Mosse YP.


Crizotinib Synergizes with Chemotherapy in Preclinical Models of Neuroblastoma. Clin Cancer Res. 2016 Feb 15;22(4):948-60.
Krytska K, Ryles HT, Sano R, Raman P, Infarinato NR, Hansel TD, Makena MR, Song MM, Reynolds CP, Mossé YP.


Exploitation of the apoptosis-primed state of MYCN-amplified neuroblastoma to develop a potent and specific targeted therapy combination. Cancer Cell. 2016 Feb 8;29(2):159-72. doi: 10.1016/j.ccell.2016.01.002. 
Ham J, Costa C, Sano R, Lochmann TL, Sennott EM, Patel NU, Dastur A, Gomez-Caraballo M, Krytska K, Hata AN, Floros KV, Hughes MT, Jakubik CT, Heisey DA, Ferrell JT, Bristol ML, March RJ, Yates C, Hicks MA, Nakajima W, Gowda M, Windle BE, Dozmorov MG, Garnett MJ, McDermott U, Harada H, Taylor SM, Morgan IM, Benes CH, Engelman JA, Mossé YP, Faber AC.


The ALK/ROS1 inhibitor PF-06463922 overcomes primary resistance to crizotinib in ALK-driven neuroblastoma. Cancer Discov. 2016 Jan;6(1):96-107. doi: 10.1158/2159-8290.CD-15-1056. Epub 2015 Nov 10.
Infarinato NR1, Park JH, Krytska K, Ryles HT, Sano R, Szigety KM, Li Y, Zou HY, Lee NV, Smeal T, Lemmon MA, Mossé YP.


ALK mutations confer differential oncogenic activation and sensitivity to ALK inhibition therapy in neuroblastoma. Cancer Cell. 2014 Nov 10;26(5):682-94.
Bresler SC, Weiser DA, Huwe PJ, Park JH, Krytska K, Ryles H, Laudenslager M, Rappaport EF, Wood AC, McGrady PW, Hogarty MD, London WB, Radhakrishnan R, Lemmon MA, Mossé YP.


Safety and activity of crizotinib for paediatric patients with refractory solid tumours or anaplastic large-cell lymphoma: a Children's Oncology Group phase 1 consortium study. Lancet Oncol. 2013 May;14(6):472-80.
Mossé YP, Lim MS, Voss SD, Wilner K, Ruffner K, Laliberte J, Rolland D, Balis FM, Maris JM, Weigel BJ, Ingle AM, Ahern C, Adamson PC, Blaney SM.


Differential inhibitor sensitivity of anaplastic lymphoma kinase variants found in neuroblastoma. Sci Transl Med. 2011 Nov 9;3(108):108ra114.
Bresler SC, Wood AC, Haglund EA, Courtright J, Belcastro LT, Plegaria JS, Cole K, Toporovskaya Y, Zhao H, Carpenter EL, Christensen JG, Maris JM, Lemmon MA, Mossé YP.


Identification of ALK as a major familial neuroblastoma predisposition gene. Nature. 2008 Oct 16;455(7215):930-5.
Mossé YP, Laudenslager M, Longo L, Cole KA, Wood A, Attiyeh EF, Laquaglia MJ, Sennett R, Lynch JE, Perri P, Laureys G, Speleman F, Kim C, Hou C, Hakonarson H, Torkamani A, Schork NJ, Brodeur GM, Tonini GP, Rappaport E, Devoto M, Maris JM.


Collaborators

Collaborators of the Mossé Laboratory from outside of the Center for Childhood Cancer Research include Mark Lemmon, PhD (Yale University), Ravi Radhakrishnan, PhD (University of Pennsylvania), Gary Johnson, PhD (University of North Carolina), Pfizer, Novartis, and FoundationOne.