of Core Service Plan: The primary purpose ofthe Molecular Profiling and Pathology (MPP) Core is to provide the investigators in this POl with a centralized and coordinated resource for the analysis of human lung cancer samples and animal model tissues using morphologic and high throughput molecular methods (histopathology, immunohistochemistry, in situ hybridization, genomic and proteomic analyses). The MPP Core functions within this POl are grouped into four logically connected Aims or activities. 1. Procurement of human lung cancer tissues for validation studies. The Core will serve as the centralized resource for validation studies using human lung cancer samples procured under several MKSCC IRBapproved protocols. For rebiopsy protocols (non-therapeutic rebiopsy after treatment initiation or rebiopsy upon progression due to presumed acquired resistance), the Gore will also serve as the main tissue repository. 2. Pathology review &analysis. The MPP core will provide expert histologic and cytologic evaluation and classification of all human lung cancer specimens used in the POl, including morphologybased assays (IHC, GISH, FISH). The MPP will also provide expert histopathologic review of lung tumors in mouse models as well as xenografted human tumors. 3. Genotyping of human lung cancer tissues for validation studies. The MPP Gore has established and is further developing prospective genotyping efforts to provide extended mutational annotation of its human lung tumor resources that is critical for rational, welldesigned validation studies biologically relevant to specific leads arising from the Research Projects. 4. Coordination of validation studies using fully annotated human lung cancer tissues. The activities described in Aims 1-3 will provide a rich collection of rigorously classified human lung cancer tissues annotated for key lung cancer genes. Studies needed to validate the discoveries generated by the individual research projects in human lung cancer tissues will be performed in or coordinated by Core personnel. Robust platforms are established for DNA, RNA and protein analytes, with the specific validation analyses being determined by the questions to be answered by the individual Research Projects.

Public Health Relevance

The MPP core will serve a critical validation function, relating the findings ofthe Research Projects to human lung carcinomas and placing them in the context of key clinical, pathologic, mutational, and genomic parameters. Consistency of diagnostic criteria and technical platforms will ensure data comparability and data exchange between projects.

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Research Program Projects (P01)
Project #
2P01CA129243-06
Application #
8393594
Study Section
Special Emphasis Panel (ZCA1-RPRB-J (M1))
Project Start
2007-07-23
Project End
2017-08-31
Budget Start
2012-09-12
Budget End
2013-08-31
Support Year
6
Fiscal Year
2012
Total Cost
$217,552
Indirect Cost
$78,620
Name
Sloan-Kettering Institute for Cancer Research
Department
Type
DUNS #
064931884
City
New York
State
NY
Country
United States
Zip Code
10065
Yu, Helena A; Perez, Leslie; Chang, Qing et al. (2017) A Phase 1/2 Trial of Ruxolitinib and Erlotinib in Patients with EGFR-Mutant Lung Adenocarcinomas with Acquired Resistance to Erlotinib. J Thorac Oncol 12:102-109
Ichihara, Eiki; Westover, David; Meador, Catherine B et al. (2017) SFK/FAK Signaling Attenuates Osimertinib Efficacy in Both Drug-Sensitive and Drug-Resistant Models of EGFR-Mutant Lung Cancer. Cancer Res 77:2990-3000
Yaeger, Rona; Yao, Zhan; Hyman, David M et al. (2017) Mechanisms of Acquired Resistance to BRAF V600E Inhibition in Colon Cancers Converge on RAF Dimerization and Are Sensitive to Its Inhibition. Cancer Res 77:6513-6523
Weigelt, Britta; Comino-Méndez, Iñaki; de Bruijn, Ino et al. (2017) Diverse BRCA1 and BRCA2 Reversion Mutations in Circulating Cell-Free DNA of Therapy-Resistant Breast or Ovarian Cancer. Clin Cancer Res 23:6708-6720
Pal, Debjani; Pertot, Anja; Shirole, Nitin H et al. (2017) TGF-? reduces DNA ds-break repair mechanisms to heighten genetic diversity and adaptability of CD44+/CD24- cancer cells. Elife 6:
Yu, H A; Sima, C; Feldman, D et al. (2017) Phase 1 study of twice weekly pulse dose and daily low-dose erlotinib as initial treatment for patients with EGFR-mutant lung cancers. Ann Oncol 28:278-284
Boire, Adrienne; Zou, Yilong; Shieh, Jason et al. (2017) Complement Component 3 Adapts the Cerebrospinal Fluid for Leptomeningeal Metastasis. Cell 168:1101-1113.e13
Nieto, Patricia; Ambrogio, Chiara; Esteban-Burgos, Laura et al. (2017) A Braf kinase-inactive mutant induces lung adenocarcinoma. Nature 548:239-243
Yao, Zhan; Yaeger, Rona; Rodrik-Outmezguine, Vanessa S et al. (2017) Tumours with class 3 BRAF mutants are sensitive to the inhibition of activated RAS. Nature 548:234-238
Drilon, Alexander; Somwar, Romel; Wagner, Jacob P et al. (2016) A Novel Crizotinib-Resistant Solvent-Front Mutation Responsive to Cabozantinib Therapy in a Patient with ROS1-Rearranged Lung Cancer. Clin Cancer Res 22:2351-8

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