Developing Personalized Medicine for Lung Cancer. The University of Texas SPORE in Lung Cancer represents a unique collaboration between the University of Texas Southwestern Medical Center (UTSW) and the University of Texas MD Anderson Cancer Center (MDACC) both of which have outstanding Strengths in lung cancer translational research. The overarching goal of the SPORE is to develop new experimental paradigms leading to personalized medicine approaches for lung cancer based on a molecular understanding of lung cancers in individual patients, and using this information to select the therapy (""""""""personalize"""""""") of each NSCLC patient's treatment. The SPORE builds on a 16 year productive history and incorporates recent advances made by SPORE investigators and others in lung cancer genomics, as well as important new advances in identifying and understanding lung cancer """"""""acquired vulnerabilities"""""""" (synthetic lethalities). Together this will provide a more complete mechanistic understanding of the molecular findings so they can be applied to patients. These advances include novel approaches to functionally classify lung cancer by determining precisely the acquired vulnerabilities of each tumor, studying new molecular classifications of NSCLC related mRNA expression and DNA mutational """"""""clades"""""""" and their functional characteristics, developing tools for CLIA certifiable molecular classification tests, preclinical model systems for testing the value of these new classification schemes, and a large legacy of molecular and clinical annotated datasets of lung cancers for retrospective analyses. The SPORE is composed of 4 projects: #1. Personalized medicine for NSCLC based on molecular portraits/""""""""clades"""""""";#2. Epidemiologic study of the role miR polymorphisms for predicting risk of lung cancer development and recurrence;#3. Therapeutic targeting of PI3K and MEK in mutant KRAS driven lung cancer for radiosensitization and blocking metastases;and #4. Therapeutic targeting of telomerase dependence on maintaining telomeres in lung cancer stem cells. In addition there are three cores: A. Administrative (including patient advocates), B. Molecular pathology, and C. Biostatistics-bioinformatics. The SPORE has some of the leading lung cancer translational investigators in the world in addition to a multidisciplinry group of clinical and laboratory scientists as well as a cadre of experienced patient advocates. The projects planned in this SPORE application will provide a new functional classification of lung cancer therapeutics, and the opportunity to change the face of NSCLC therapy.

Public Health Relevance

This SPORE in Lung Cancer assembles a multidisciplinary team of clinical and basic scientists from two leading lung cancer research institutions (UTSW and MDACC) to develop new ways to diagnose and treat lung cancer based on a rationale understanding of its molecular underpinnings and thus provide new personalized medicine for lung cancer.

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Specialized Center (P50)
Project #
2P50CA070907-16A1
Application #
8738108
Study Section
Special Emphasis Panel (ZCA1-RPRB-C (M1))
Program Officer
Ujhazy, Peter
Project Start
1996-09-30
Project End
2019-08-31
Budget Start
2014-09-23
Budget End
2015-08-31
Support Year
16
Fiscal Year
2014
Total Cost
$2,161,999
Indirect Cost
$433,224
Name
University of Texas Sw Medical Center Dallas
Department
Internal Medicine/Medicine
Type
Schools of Medicine
DUNS #
800771545
City
Dallas
State
TX
Country
United States
Zip Code
75390
Goodwin, Justin; Neugent, Michael L; Lee, Shin Yup et al. (2017) The distinct metabolic phenotype of lung squamous cell carcinoma defines selective vulnerability to glycolytic inhibition. Nat Commun 8:15503
Cao, Xiaobo; Zhao, Yang; Wang, Jing et al. (2017) TUSC2 downregulates PD-L1 expression in non-small cell lung cancer (NSCLC). Oncotarget 8:107621-107629
Zhou, Fei; Wang, Yanru; Liu, Hongliang et al. (2017) Susceptibility loci of CNOT6 in the general mRNA degradation pathway and lung cancer risk-A re-analysis of eight GWASs. Mol Carcinog 56:1227-1238
Tagal, Vural; Wei, Shuguang; Zhang, Wei et al. (2017) SMARCA4-inactivating mutations increase sensitivity to Aurora kinase A inhibitor VX-680 in non-small cell lung cancers. Nat Commun 8:14098
Jafri, Mohammad Alam; Al-Qahtani, Mohammed Hussein; Shay, Jerry William (2017) Role of miRNAs in human cancer metastasis: Implications for therapeutic intervention. Semin Cancer Biol 44:117-131
Cardnell, Robert J; Li, Lerong; Sen, Triparna et al. (2017) Protein expression of TTF1 and cMYC define distinct molecular subgroups of small cell lung cancer with unique vulnerabilities to aurora kinase inhibition, DLL3 targeting, and other targeted therapies. Oncotarget 8:73419-73432
Faubert, Brandon; Li, Kevin Y; Cai, Ling et al. (2017) Lactate Metabolism in Human Lung Tumors. Cell 171:358-371.e9
Rabellino, Andrea; Andreani, Cristina; Scaglioni, Pier Paolo (2017) The Role of PIAS SUMO E3-Ligases in Cancer. Cancer Res 77:1542-1547
Fu, Rong; Wang, Pei; Ma, Weiping et al. (2017) A statistical method for detecting differentially expressed SNVs based on next-generation RNA-seq data. Biometrics 73:42-51
Quek, Kelly; Li, Jun; Estecio, Marcos et al. (2017) DNA methylation intratumor heterogeneity in localized lung adenocarcinomas. Oncotarget 8:21994-22002

Showing the most recent 10 out of 1004 publications