Shiao-Wen David Hsu

Positions:

Associate Professor of Medicine

Medicine, Medical Oncology
School of Medicine

William Dalton Family Assistant Professor of Medical Oncology, in the School of Medicine

Medicine, Medical Oncology
School of Medicine

Member of the Duke Cancer Institute

Duke Cancer Institute
School of Medicine

Education:

M.D. 2001

University of North Carolina at Chapel Hill

Medical Resident, Medicine

University of Texas at Dallas

Fellow in Hematology-Oncology, Medicine

Duke University

Grants:

Identifying gene-environment interactions that confer metabolic vulnerabilities in cancer

Administered By
Pharmacology & Cancer Biology
Awarded By
National Institutes of Health
Role
Collaborator
Start Date
End Date

Targeting KRAS (G12C) Mutant in Colorectal Cancer

Administered By
Medicine, Medical Oncology
Role
Principal Investigator
Start Date
End Date

Determining the Efficacy of Liposomal Gemcitabine in Patient Derived Xenografts (PDXs)

Administered By
Medicine, Medical Oncology
Role
Principal Investigator
Start Date
End Date

Targeting the TK1 receptor in colorectal and lung PDX using CarT cell and Motorcar cell

Administered By
Medicine, Medical Oncology
Role
Principal Investigator
Start Date
End Date

Targeting Calreticulin in Colorectal Cancer Liver Metastasis

Administered By
Medicine, Medical Oncology
Awarded By
National Institutes of Health
Role
Principal Investigator
Start Date
End Date

Publications:

miR-1269 promotes metastasis and forms a positive feedback loop with TGF-β.

As patient survival drops precipitously from early-stage cancers to late-stage and metastatic cancers, microRNAs that promote relapse and metastasis can serve as prognostic and predictive markers as well as therapeutic targets for chemoprevention. Here we show that miR-1269a promotes colorectal cancer (CRC) metastasis and forms a positive feedback loop with TGF-β signalling. miR-1269a is upregulated in late-stage CRCs, and long-term monitoring of 100 stage II CRC patients revealed that miR-1269a expression in their surgically removed primary tumours is strongly associated with risk of CRC relapse and metastasis. Consistent with clinical observations, miR-1269a significantly increases the ability of CRC cells to invade and metastasize in vivo. TGF-β activates miR-1269 via Sox4, while miR-1269a enhances TGF-β signalling by targeting Smad7 and HOXD10, hence forming a positive feedback loop. Our findings suggest that miR-1269a is a potential marker to inform adjuvant chemotherapy decisions for CRC patients and a potential therapeutic target to deter metastasis.
Authors
Bu, P; Wang, L; Chen, K-Y; Rakhilin, N; Sun, J; Closa, A; Tung, K-L; King, S; Kristine Varanko, A; Xu, Y; Huan Chen, J; Zessin, AS; Shealy, J; Cummings, B; Hsu, D; Lipkin, SM; Moreno, V; Gümüş, ZH; Shen, X
MLA Citation
Bu, Pengcheng, et al. “miR-1269 promotes metastasis and forms a positive feedback loop with TGF-β..” Nat Commun, vol. 6, Apr. 2015. Pubmed, doi:10.1038/ncomms7879.
URI
https://scholars.duke.edu/individual/pub1063491
PMID
25872451
Source
pubmed
Published In
Nature Communications
Volume
6
Published Date
Start Page
6879
DOI
10.1038/ncomms7879

Predictive and prognostic biomarkers in colorectal cancer

Colorectal cancer is the third most common cancer and the second leading cause of cancer-related death in the United States. Three quarters of patients diagnosed with colorectal cancer will have early stage disease and despite surgical resection for curative intent, approximately 20%-25% of patients will recur with their disease within five years. The other 25% will present with advanced or metastatic disease and clinicians are faced with the challenge of choosing the most appropriate therapy for individual patients. Despite multiple treatment options which are now available and concomitant improvements in survival, advanced colorectal cancer remains universally fatal. The challenge for clinicians is to identify prognostic and predictive biomarkers that can assist in tailoring available treatments for an individual patient to improve clinical outcomes. This review will summarize current and future biomarkers in colorectal cancer and discuss their utility in managing patient care. © 2011 Higher Education Press and Springer-Verlag Berlin Heidelberg.
MLA Citation
van Deusen, J., and D. S. Hsu. “Predictive and prognostic biomarkers in colorectal cancer.” Frontiers in Biology, vol. 6, no. 6, Dec. 2011, pp. 482–89. Scopus, doi:10.1007/s11515-011-1158-y.
URI
https://scholars.duke.edu/individual/pub777455
Source
scopus
Published In
Frontiers in Biology
Volume
6
Published Date
Start Page
482
End Page
489
DOI
10.1007/s11515-011-1158-y

Young age at diagnosis correlates with worse prognosis and defines a subset of breast cancers with shared patterns of gene expression.

PURPOSE: Breast cancer arising in young women is correlated with inferior survival and higher incidence of negative clinicopathologic features. The biology driving this aggressive disease has yet to be defined. PATIENTS AND METHODS: Clinically annotated, microarray data from 784 early-stage breast cancers were identified, and prospectively defined, age-specific cohorts (young: </= 45 years, n = 200; older: >/= 65 years, n = 211) were compared by prognosis, clinicopathologic variables, mRNA expression values, single-gene analysis, and gene set enrichment analysis (GSEA). Univariate and multivariate analyses were performed. RESULTS: Using clinicopathologic variables, young women illustrated lower estrogen receptor (ER) positivity (immunohistochemistry [IHC], P = .027), larger tumors (P = .012), higher human epidermal growth factor receptor 2 (HER-2) overexpression (IHC, P = .075), lymph node positivity (P = .008), higher grade tumors (P < .0001), and trends toward inferior disease-free survival (DFS; hazard ratio = 1.32; P = .094). Using genomic expression analysis, tumors arising in young women had significantly lower ERalpha mRNA (P < .0001), ERbeta (P = .02), and progesterone receptor (PR) expression (P < .0001), but higher HER-2 (P < .0001) and epidermal growth factor receptor (EGFR) expression (P < .0001). Exploratory analysis (GSEA) revealed 367 biologically relevant gene sets significantly distinguishing breast tumors arising in young women. Combining clinicopathologic and genomic variables among tumors arising in young women demonstrated that younger age and lower ERbeta and higher EGFR mRNA expression were significant predictors of inferior DFS. CONCLUSION: This large-scale genomic analysis illustrates that breast cancer arising in young women is a unique biologic entity driven by unifying oncogenic signaling pathways, is characterized by less hormone sensitivity and higher HER-2/EGFR expression, and warrants further study to offer this poor-prognosis group of women better preventative and therapeutic options.
Authors
Anders, CK; Hsu, DS; Broadwater, G; Acharya, CR; Foekens, JA; Zhang, Y; Wang, Y; Marcom, PK; Marks, JR; Febbo, PG; Nevins, JR; Potti, A; Blackwell, KL
MLA Citation
Anders, Carey K., et al. “Young age at diagnosis correlates with worse prognosis and defines a subset of breast cancers with shared patterns of gene expression..” J Clin Oncol, vol. 26, no. 20, July 2008, pp. 3324–30. Pubmed, doi:10.1200/JCO.2007.14.2471.
URI
https://scholars.duke.edu/individual/pub760986
PMID
18612148
Source
pubmed
Published In
Journal of Clinical Oncology
Volume
26
Published Date
Start Page
3324
End Page
3330
DOI
10.1200/JCO.2007.14.2471

Mismatch repair gone awry: Management of Lynch syndrome.

The hallmark of Lynch syndrome involves germline mutations of genes important in DNA mismatch repair. Affected family kindreds will have multiple associated malignancies, the most common of which is colorectal adenocarcinoma. Recently, evidence has shown that clinical diagnostic criteria provided by the Amsterdam Criteria and the Bethesda Guidelines must be linked with microsatellite instability testing to correctly diagnose Lynch syndrome. We present a case of metachronous colorectal adenocarcinomas in a patient less than 50 years of age, followed by a discussion of Lynch syndrome, with an emphasis on surveillance and prevention of malignancies.
Authors
Zhang, T; Boswell, EL; McCall, SJ; Hsu, DS
MLA Citation
Zhang, Tian, et al. “Mismatch repair gone awry: Management of Lynch syndrome..” Crit Rev Oncol Hematol, vol. 93, no. 3, Mar. 2015, pp. 170–79. Pubmed, doi:10.1016/j.critrevonc.2014.10.005.
URI
https://scholars.duke.edu/individual/pub1051217
PMID
25459670
Source
pubmed
Published In
Crit Rev Oncol Hematol
Volume
93
Published Date
Start Page
170
End Page
179
DOI
10.1016/j.critrevonc.2014.10.005

Retraction for Garman et al: A genomic approach to colon cancer risk stratification yields biologic insights into therapeutic opportunities.

Authors
Garman, KS; Acharya, CR; Edelman, E; Grade, M; Gaedcke, J; Sud, S; Barry, W; Diehl, AM; Provenzale, D; Ginsburg, GS; Ghadimi, BM; Ried, T; Nevins, JR; Mukherjee, S; Hsu, D; Potti, A
MLA Citation
Garman, Katherine S., et al. “Retraction for Garman et al: A genomic approach to colon cancer risk stratification yields biologic insights into therapeutic opportunities..” Proc Natl Acad Sci U S A, vol. 108, no. 42, Oct. 2011. Pubmed, doi:10.1073/pnas.1115170108.
URI
https://scholars.duke.edu/individual/pub768489
PMID
21969600
Source
pubmed
Published In
Proc Natl Acad Sci U S A
Volume
108
Published Date
Start Page
17569
DOI
10.1073/pnas.1115170108