Contribution to Science

Research

1.The Role of chromosome 3q amplification in lung cancer

Historical background:  Genomic instability is a key attributes of cell undergoing transformation. Chromosomal alterations are a key feature of malignant transformation. The 3q amplicon is one of the most prevalent and persistent genomic alterations in smoking related epithelial malignancies including lung cancer.  Central findings: We have established the amplicon develops before the tumor has acquired invasive properties. We identified key contributors to tumorigenesis in this amplicon including PIK3CA, TP63, ECT2, PRKCI and FXR1. We established FXR1 as a novel oncogenic driver and able to work in concert with other genes in the same amplicon. Influence of findings:  We have established the molecular basis for the role of this amplicon in NSCLC, we identified this genomic alterations as a potential candidate biomarkers of progression among preinvasive lesions and discovered that RNA binding proteins may play a key role in tumor development. Role:  Principal Investigator

Relevant peer-reviewed publications:

  • Massion PP, Kuo WL, Stokoe D, Olshen AB, Treseler PA, Chin K, Chen C, Polikoff D, Jain AN, Pinkel D, Albertson DG, Jablons DM, Gray JW. Genomic copy number analysis of non-small cell lung cancer using array comparative genomic hybridization: implications of the phosphatidylinositol 3-kinase pathway. Cancer Res. 62:3636-40, 2002.
  • Massion PP, Taflan PM, Jamshedur Rahman SM, Yildiz P, Shyr Y, Edgerton ME, Westfall MD, Roberts JR, Pietenpol JA, Carbone DP, Gonzalez AL. Significance of p63 Amplification and overexpression in lung cancer development and prognosis. Cancer Res. 63:7113-21, 2003.
  • Qian J, Hassanein M, Hoeksema MD, Harris BK, Zou Y, Chen H, Lu P, Eisenberg R, Wang J, Espinosa A, Ji X, Harris FT, Rahman SM, Massion PP. The RNA binding protein FXR1 is a new driver in the 3q26-29 amplicon and predicts poor prognosis in human cancers. Proc Natl Acad Sci USA. 112:3469-74, 2015.
  • Wang J, Qian J, Hoeksema MD, Zou Y, Espinosa AV, Rahman SM, Zhang B, Massion PP. Integrative genomics analysis identifies candidate drivers at 3q26-29 amplicon in squamous cell carcinoma of the lung. Clin Cancer Res. 19:5580-90, 2013.

 

2. Field of cancerization and metabolic alterations.

Historical background:  The airway epithelium represents a large field of injury where cells get exposed to carcinogens. Those lead to stochastic DNA alterations which eventually predisposes to tumor formation. We undertook an in depth proteomic and genomic analysis of these alterations in search for determinants of lung cancer progression. We discovered metabolic alterations in high risk individuals and in early lung cancer.

Influence of findings:  We identified genomic and proteomic alterations suggesting of lung cancer progression. We tested these attributes functionally to discover some key molecular determinants of lung cancer progression.  Role:  Principal Investigator

Relevant peer-reviewed publications:

  • Rahman SM, Gonzalez AL, Li M, Seeley EH, Zimmerman LJ, Zhang XJ, Manier ML, Olson SJ, Shah RN, Miller AN, Putnam JB, Miller YE, Franklin WA, Blot WJ, Carbone DP, Shyr Y, Caprioli RM, Massion PP. Lung cancer diagnosis from proteomic analysis of preinvasive lesions. Cancer Res. 71:3009-17, 2011.
  • Hassanein, M., Hoeksema, M.D., Shiota, M., Qian, J., Harris, B.K., Chen, H., Clark, J.E., Alborn, W.E., Eisenberg, R., Massion, P.P. SLC1A5 mediates glutamine transport required for lung cancer cell growth and survival. Clin. Cancer Res. 19(3):560-70, 2013. PMCID: PMC3697078
  • Gustafson AM, Soldi R, Anderlind C, Scholand MB, Qian J, Zhang X, Cooper K, Walker D, McWilliams A, Liu G, Szabo E, Brody J, Massion PP, Lenburg, ME, Lam S, Bild AH, Spira A. Airway PI3K pathway activation is an early and reversible event in lung cancer development. Sci Transl Med. 2:26ra5, 2010.
  • Rahman, S. M., X. Ji, L. J. Zimmerman, M. Li, B. K. Harris, M. D. Hoeksema, I. A. Trenary, Y. Zou, J. Qian, R. J. Slebos, J. Beane, A. Spira, Y. Shyr, R. Eisenberg, D. C. Liebler, J. D. Young, and P. P. Massion. 'The airway epithelium undergoes metabolic reprogramming in individuals at high risk for lung cancer', JCI Insight, 2016.1: e88814

 

3. Non-invasive evaluation of indeterminate pulmonary nodules (IPNs).

Historical background:  The management of IPNs represents one of the most urgent clinical problems arising from lung cancer screening. We are testing the hypothesis that integrating clinical, advanced imaging and molecular techniques will optimize the diagnostic accuracy for IPN. Influence of findings:  We demonstrated proof of concept to improve early discrimination of benign from malignant IPNs and to minimize unnecessary invasive procedures. This work should revolutionize the field, leading to improved individualized management of IPNs.Role:  Principal investigator

Relevant peer-reviewed publications:

  • Li XJ, Hayward C, Fong PY, Dominguez M, Hunsucker SW, Lee LW, McLean M, Law S, Butler H, Schirm M, Gingras O, Lamontagne J, Allard R, Chelsky D, Price ND, Lam S, Massion PP, Pass H, Rom WN, Vachani A, Fang KC, Hood L, Kearney P. A blood-based proteomic classifier for the molecular characterization of pulmonary nodules. Sci Transl Med. 5:207ra142, 2013.
  • Deppen SA, Blume JD, Kensinger CD, Morgan AM, Aldrich MC, Massion PP, Walker RC, McPheeters ML, Putnam JP Jr, Grogan EL. Accuracy of FDG-PET to diagnose lung cancer in areas with infectious lung disease: a meta-analysis. JAMA. 312:1227-36, 2014.
  • Vachani A, Pass HI, Rom WN, Midthun DE, Edell ES, Laviolette M, Li XJ, Fong PY, Hunsucker SW, Hayward C, Mazzone PJ, Madtes DK, Miller YE, Walker MG, Shi J, Kearney P, Fang KC, Massion PP. Validation of a multiprotein plasma classifier to identify benign lung nodules. J Thorac Oncol. 10(4):629-37, 2015.
  • Liu, Y., Y. Balagurunathan, T. Atwater, S. Antic, Q. Li, R. C. Walker, G. Smith, P. P. Massion, M. B. Schabath, and R. J. Gillies. 'Radiological Image traits Predictive of Cancer Status in Pulmonary Nodules', Clin Cancer Res. 2016. Epub

 

4. Tumor heterogeneity in SCLC.

Historical background:  Small cell lung cancer is a recalcitrant lung tumor that carries the worst prognosis. There has been no significant in outcome in the last 30 years.  We discovered genomic alterations in SCLC that are centered on neuroendocrine biology and cellular differentiation. Influence of findings:  We characterized new candidate targets in SCLC including FAK and SYK kinases. We have established a basis for potential new therapeutic strategies. More recently we characterized its cellular heterogeneity and identified two phenotypes mesenchymal and neuroendocrine with specific adhesion properties, biomarkers and transcription factor profiles. Role:  Principal investigator

Relevant peer-reviewed publications:

  • Ocak S, Yamashita H, Udyavar AR, Miller AN, Gonzalez AL, Zou Y, Jiang A, Yi Y, Shyr Y, Estrada L, Quaranta V, Massion PP. DNA copy number aberrations in small-cell lung cancer reveal activation of the focal adhesion pathway. Oncogene. 2010;29:6331-42.
  • Ocak S, Friedman DB, Chen H, Ausborn JA, Hassanein M, Detry B, Weyland B, Aboubakar F, Pilette C, Sibille Y, Massion PP. Discovery of new membrane-associated proteins overexpressed in small-cell lung cancer. J Thorac Oncol. 9:324-36, 2014.
  • Udyavar AR, Hoeksema MD, Clark JE, Zou Y, Tang Z, Li Z, Li M, Chen H, Statnikov A, Shyr Y, Liebler DC, Field J, Eisenberg R, Estrada L, Massion PP, Quaranta V. Co-expression network analysis identifies Spleen Tyrosine Kinase (SYK) as a candidate oncogenic driver in a subset of small-cell lung cancer. BMC Syst Biol. 7 Suppl 5:S1, 2013.
  • Udyavar, A. R., D. J. Wooten, M. D. Hoeksema, M. Bansal, A. Califano, L. Estrada, S. Schnell, J. M. Irish, P. P. Massion, and V. Quaranta. 'Novel hybrid phenotype revealed in Small Cell Lung Cancer by a transcription factor network model that can explain tumor heterogeneity', Cancer Res 2016. Epub

 

For a full list of publications on PubMed

 

Clinical Trials

Nashville Early Diagnosis Lung Cancer Project

ClinicalTrials.gov Identifier:
NCT01475500

Locations
Meharry Medical Center -----Recruiting
Nashville, Tennessee, United States, 37232
Contact: Clinical Trials Reporting Program    800-811-8480      
Contact: Anel Muterspaugh    615-875-6099  

Vanderbilt University, Vanderbilt-Ingram Cancer Center -----Recruiting
Nashville, Tennessee, United States, 37232
Contact: Clinical Trials Information Program    800-811-8480      
Contact: Anel Muterspaugh    615-936-4244 

Veterans Administration -----Recruiting
Nashville, Tennessee, United States, 37212
Contact: Sanja Antic    615-875-6099      
Principal Investigator: Pierre P Massion, MD

Molecular Predictors of Cancer in Patients at High Risk of Lung Cancer

ClinicalTrials.gov Identifier:
NCT00898313

Location

Vanderbilt-Ingram Cancer Center -----Recruiting
Nashville, Tennessee, United States, 37212
Contact: VICC Clinical Trials Information Program    800-811-8480    cip@vanderbilt.edu   
Principal Investigator: Pierre Massion, MD         

Veterans Affairs Medical Center - Nashville -----Recruiting
Nashville, Tennessee, United States, 37212
Contact: Research Office    615-873-8066      
Contact: Rena Burns, RN    (615) 873-7658    Rena.Burns@va.gov   
Principal Investigator: Pierre Massion, MD         


​Collecting and Analyzing Tissue Samples From Patients Undergoing Surgery for Non- Small Lung Cancer


ClinicalTrials.gov Identifier:
NCT00897117

​Locations

Dan Rudy Cancer Center at Saint Thomas Hospital -----Recruiting
Nashville, Tennessee, United States, 37205
Contact: Contact Person    615-222-2166 

Vanderbilt University, Vanderbilt-Ingram Cancer Center -----Recruiting
Nashville, Tennessee, United States, 37232
Contact: Clinical Trials Information Program    800-811-8480      
Contact: Anel Muterspaugh    615-936-4244 

Veterans Administration -----Recruiting
Nashville, Tennessee, United States, 37212
Contact: Sanja Antic    615-875-6099      
Principal Investigator: Pierre P Massion, MD

DECAMP-1: Diagnosis and Surveillance of Indeterminate Pulmonary Nodules

ClinicalTrials.gov Identifier:
NCT01785342


Nashville Location

Middle Tennessee Research Institute (Vanderbilt University) -----Recruiting
Nashville, Tennessee, United States
Contact: Rena Burns rena.burns@va.gov   
Principal Investigator: Pierre Massion, MD

A Case-Control Study to Verify Diagnostic Performance of AminoIndex Technology


ClinicalTrials.gov Identifier:
NCT02512757

Location
Vanderbilt-Ingram Cancer Center (VICC) -----Recruiting
Nashville, Tennessee, United States, 37232
Contact: VICC Clinical Trials Reporting Program    800-811-8480      

 

18F-FSPG PET/CT in Imaging Patients With Newly Diagnosed Lung Cancer or Indeterminate Pulmonary Nodules


ClinicalTrials.gov Identifier:
NCT02448225

Location

Vanderbilt-Ingram Cancer Center -----Recruiting
Nashville, Tennessee, United States, 37232
Principal Investigator: Pierre Massion, MD         

Early Diagnosis of Pulmonary Nodules


ClinicalTrials.gov Identifier:
NCT01752114

Location

Vanderbilt-Ingram Cancer Center
Nashville, Tennessee, United States, 37212
Contact: VICC Clinical Trials Information Program    800-811-8480    cip@vanderbilt.edu