Marvaretta Stevenson

Positions:

Assistant Professor of Medicine

Medicine, Medical Oncology
School of Medicine

Member of the Duke Cancer Institute

Duke Cancer Institute
School of Medicine

Education:

M.D. 2004

Medical University of South Carolina School of Medicine

Resident

Duke University School of Medicine

Publications:

Characterizing the clinical relevance of an embryonic stem cell phenotype in lung adenocarcinoma.

PURPOSE: Cancer cells possess traits reminiscent of those ascribed to normal stem cells. It is unclear whether these phenotypic similarities are the result of a common biological phenotype, such as regulatory pathways. EXPERIMENTAL DESIGN: Lung cancer cell lines with corresponding gene expression data and genes associated with an embryonic stem cell identity were used to develop a signature of embryonic stemness (ES) activity specific to lung adenocarcinoma. Biological characteristics were elucidated as a function of cancer biology/oncogenic pathway dysregulation. The ES signature was applied to three independent early-stage (I-IIIa) lung adenocarcinoma data sets with clinically annotated gene expression data. The relationship between the ES phenotype and cisplatin (current standard of care) sensitivity was evaluated. RESULTS: Pathway analysis identified specific regulatory networks [Ras (P = 0.0005), Myc (P = 0.0224), wound healing (P < 0.0001), chromosomal instability (P < 0.0001), and invasiveness (P < 0.0001)] associated with the ES phenotype. The prognostic relevance of the ES signature, as related to patient survival, was characterized in three cohorts [CALGB 9761 (n = 82; P = 0.0001), National Cancer Institute Director's Challenge Consortium (n = 442; P = 0.0002), and Duke (n = 45; P = 0.06)]. The ES signature was not prognostic in prostate, breast, or ovarian adenocarcinomas. Lung tumors (n = 569) and adenocarcinoma cell lines (n = 31) expressing the ES phenotype were more likely to be resistant to cisplatin (P < 0.0001 and P = 0.006, respectively). CONCLUSIONS: Lung adenocarcinomas that share a common gene expression pattern with normal human embryonic stem cells were associated with decreased survival, increased biological complexity, and increased likelihood of resistance to cisplatin. This indicates the aggressiveness of these tumors.
Authors
Stevenson, M; Mostertz, W; Acharya, C; Kim, W; Walters, K; Barry, W; Higgins, K; Tuchman, SA; Crawford, J; Vlahovic, G; Ready, N; Onaitis, M; Potti, A
MLA Citation
Stevenson, Marvaretta, et al. “Characterizing the clinical relevance of an embryonic stem cell phenotype in lung adenocarcinoma.Clin Cancer Res, vol. 15, no. 24, Dec. 2009, pp. 7553–61. Pubmed, doi:10.1158/1078-0432.CCR-09-1939.
URI
https://scholars.duke.edu/individual/pub722415
PMID
19996213
Source
pubmed
Published In
Clinical Cancer Research : an Official Journal of the American Association for Cancer Research
Volume
15
Published Date
Start Page
7553
End Page
7561
DOI
10.1158/1078-0432.CCR-09-1939

Age-specific differences in oncogenic pathway dysregulation and anthracycline sensitivity in patients with acute myeloid leukemia.

PURPOSE: To define the biology driving the aggressive nature of acute myeloid leukemia (AML) in elderly patients. PATIENTS AND METHODS: Clinically annotated microarray data from 425 patients with newly diagnosed de novo AML from two publicly available data sets were analyzed after age-specific cohorts (young <or= 45 years, n = 175; elderly >or= 55 years; n = 144) were prospectively identified. Gene expression analysis was conducted utilizing gene set enrichment analysis, and by applying previously defined and tested signature profiles reflecting dysregulation of oncogenic signaling pathways, altered tumor environment, and signatures of chemotherapy sensitivity. RESULTS: Elderly AML patients as expected had worse overall survival and event-free survival compared with younger patients. Analysis of oncogenic pathways revealed that older patients had higher probability of RAS, Src, and tumor necrosis factor (TNF) pathway activation (all P < .0001). Older patients were also less sensitive to anthracycline compared with younger patients with AML (P < .0001). Hierarchical clustering revealed that younger AML patients in cluster 2 had clinically worse survival, with high RAS, Src, and TNF pathway activation and in turn were less sensitive to anthracycline compared with patients in cluster 1. However, among elderly patients with AML, those in cluster 1 also demonstrated high RAS, Src, and TNF pathway activation but this did not translate into differences in survival or anthracycline sensitivity. CONCLUSION: AML in the elderly represents a distinct biologic entity characterized by unique patterns of deregulated signaling pathway variations that contributes to poor survival and anthracycline resistance. These insights should enable development and adjustments of clinically meaningful treatment strategies in the older patient population.
Authors
Rao, AV; Valk, PJM; Metzeler, KH; Acharya, CR; Tuchman, SA; Stevenson, MM; Rizzieri, DA; Delwel, R; Buske, C; Bohlander, SK; Potti, A; Löwenberg, B
MLA Citation
Rao, Arati V., et al. “Age-specific differences in oncogenic pathway dysregulation and anthracycline sensitivity in patients with acute myeloid leukemia.J Clin Oncol, vol. 27, no. 33, Nov. 2009, pp. 5580–86. Pubmed, doi:10.1200/JCO.2009.22.2547.
URI
https://scholars.duke.edu/individual/pub733330
PMID
19858393
Source
pubmed
Published In
Journal of Clinical Oncology
Volume
27
Published Date
Start Page
5580
End Page
5586
DOI
10.1200/JCO.2009.22.2547

Characterizing the developmental pathways TTF-1, NKX2-8, and PAX9 in lung cancer.

We investigated the clinical implications of lung developmental transcription factors (TTF-1, NKX2-8, and PAX9) that we recently discovered as cooperating oncogenes activated by way of gene amplification at chromosome 14q13 in lung cancer. Using stable transfectants of human bronchial epithelial cells, RNA expression profiles (signatures) representing activation of the biological pathways defined by each of the 3 genes were determined and used to risk stratify a non-small-cell lung cancer (NSCLC) clinical data set consisting of 91 early stage tumors. Coactivation of the TTF-1 and NKX2-8 pathways identified a cluster of patients with poor survival, representing approximately 20% of patients with early stage NSCLC, whereas activation of individual pathways did not reveal significant prognostic power. Importantly, the poor prognosis associated with coactivation of TTF-1 and NKX2-8 was validated in 2 other independent clinical data sets. Furthermore, lung cancer cell lines showing coactivation of the TTF-1 and NKX2-8 pathways were shown to exhibit resistance to cisplatin, the standard of care for the treatment of NSCLC. This suggests that the cohort of patients with coactivation of TTF-1 and NKX2-8 pathways appears to be resistant to standard cisplatin therapy, suggesting the need for alternative therapies in this cohort of high-risk patients.
Authors
Hsu, DS; Acharya, CR; Balakumaran, BS; Riedel, RF; Kim, MK; Stevenson, M; Tuchman, S; Mukherjee, S; Barry, W; Dressman, HK; Nevins, JR; Powers, S; Mu, D; Potti, A
MLA Citation
Hsu, David S., et al. “Characterizing the developmental pathways TTF-1, NKX2-8, and PAX9 in lung cancer.Proc Natl Acad Sci U S A, vol. 106, no. 13, Mar. 2009, pp. 5312–17. Pubmed, doi:10.1073/pnas.0900827106.
URI
https://scholars.duke.edu/individual/pub769524
PMID
19279207
Source
pubmed
Published In
Proc Natl Acad Sci U S A
Volume
106
Published Date
Start Page
5312
End Page
5317
DOI
10.1073/pnas.0900827106

Tumor acquisition for biomarker research in lung cancer.

The biopsy collection data from two lung cancer trials that required fresh tumor samples be obtained for microarray analysis were reviewed. In the trial for advanced disease, microarray data were obtained on 50 patient samples, giving an overall success rate of 60.2%. The majority of the specimens were obtained through CT-guided lung biopsies (N = 30). In the trial for early-stage patients, 28 tissue specimens were collected from excess tumor after surgical resection with a success rate of 85.7%. This tissue procurement program documents the feasibility in obtaining fresh tumor specimens prospectively that could be used for molecular testing.
Authors
MLA Citation
Stevenson, Marvaretta, et al. “Tumor acquisition for biomarker research in lung cancer.Cancer Invest, vol. 32, no. 6, July 2014, pp. 291–98. Pubmed, doi:10.3109/07357907.2014.911880.
URI
https://scholars.duke.edu/individual/pub1029675
PMID
24810245
Source
pubmed
Published In
Cancer Invest
Volume
32
Published Date
Start Page
291
End Page
298
DOI
10.3109/07357907.2014.911880

Occult primary, version 3.2014.

The NCCN Guidelines for Occult Primary tumors provide recommendations for the evaluation, workup, management, and follow-up of patients with occult primary tumors (cancers of unknown primary). These NCCN Guidelines Insights summarize major discussion points of the 2014 NCCN Occult Primary panel meeting. The panel discussed gene expression profiling (GEP) for the identification of the tissue of origin and concluded that, although GEP has a diagnostic benefit, a clinical benefit has not been demonstrated. The panel recommends against GEP as standard management, although 20% of the panel believes the diagnostic benefit of GEP warrants its routine use. In addition, the panel discussed testing for actionable mutations (eg, ALK) to help guide choice of therapy, but declined to add this recommendation.
Authors
Ettinger, DS; Handorf, CR; Agulnik, M; Bowles, DW; Cates, JM; Cristea, M; Dotan, E; Eaton, KD; Fidias, PM; Gierada, D; Gilcrease, GW; Godby, K; Iyer, R; Lenzi, R; Phay, J; Rashid, A; Saltz, L; Schwab, RB; Shulman, LN; Smerage, JB; Stevenson, MM; Varadhachary, GR; Zager, JS; Zhen, WK; Bergman, MA; Freedman-Cass, DA; National Comprehensive Cancer Network,
MLA Citation
Ettinger, David S., et al. “Occult primary, version 3.2014.J Natl Compr Canc Netw, vol. 12, no. 7, July 2014, pp. 969–74. Pubmed, doi:10.6004/jnccn.2014.0093.
URI
https://scholars.duke.edu/individual/pub1034733
PMID
24994917
Source
pubmed
Published In
J Natl Compr Canc Netw
Volume
12
Published Date
Start Page
969
End Page
974
DOI
10.6004/jnccn.2014.0093