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 - 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
Awarded By
Amgen, Inc.
Role
Principal Investigator
Start Date
End Date

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

Administered By
Medicine, Medical Oncology
Awarded By
FUJIFILM Pharmaceuticals U.S.A.
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
Awarded By
Thunder Biotech
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:

Identification of DK419, a potent inhibitor of Wnt/β-catenin signaling and colorectal cancer growth.

The Wnt signaling pathway is critical for normal tissue development and is an underlying mechanism of disease when dysregulated. Previously, we reported that the drug Niclosamide inhibits Wnt/β-catenin signaling by decreasing the cytosolic levels of Dishevelled and β-catenin, and inhibits the growth of colon cancers both in vitro and in vivo. Since the discovery of Niclosamide's anthelmintic activity, a growing body of literature indicates that Niclosamide is a multifunctional drug. In an effort to identify derivatives of Niclosamide with improved pharmacokinetic properties that maintain the multifunctional drug activity of Niclosamide for clinical evaluation, we designed DK419, a derivative containing a 1H-benzo[d]imidazole-4-carboxamide substructure, using the structure-activity relationships (SAR) of the Niclosamide salicylanilide chemotype. Similar to Niclosamide, we found DK419 inhibited Wnt/β-catenin signaling, altered cellular oxygen consumption rate and induced production of pAMPK. Moreover, we found DK419 inhibited the growth of CRC tumor cells in vitro, had good plasma exposure when dosed orally, and inhibited the growth of patient derived CRC240 tumor explants in mice dosed orally. DK419, a derivative of Niclosamide with multifunctional activity and improved pharmacokinetic properties, is a promising agent to treat colorectal cancer, Wnt-related diseases and other diseases in which Niclosamide has demonstrated functional activity.
Authors
Wang, J; Mook, RA; Ren, X-R; Zhang, Q; Jing, G; Lu, M; Spasojevic, I; Lyerly, HK; Hsu, D; Chen, W
MLA Citation
Wang, Jiangbo, et al. “Identification of DK419, a potent inhibitor of Wnt/β-catenin signaling and colorectal cancer growth.Bioorg Med Chem, vol. 26, no. 20, Nov. 2018, pp. 5435–42. Pubmed, doi:10.1016/j.bmc.2018.09.016.
URI
https://scholars.duke.edu/individual/pub1353138
PMID
30274939
Source
pubmed
Published In
Bioorg Med Chem
Volume
26
Published Date
Start Page
5435
End Page
5442
DOI
10.1016/j.bmc.2018.09.016

A phase II study of capecitabine, oxaliplatin, and bevacizumab in the treatment of metastatic esophagogastric adenocarcinomas.

BACKGROUND: Esophageal and gastric cancers often present at an advanced stage. Systemic chemotherapy is the mainstay of treatment, but survival with current regimens remains poor. We evaluated the safety, tolerability, and efficacy of the combination capecitabine, oxaliplatin, and bevacizumab in the treatment of metastatic esophagogastric adenocarcinomas. METHODS: Thirty-seven patients with metastatic or unresectable gastric/gastroesophageal junction tumors were enrolled and treated with capecitabine 850 mg/m(2) BID on days 1-14, and oxaliplatin 130 mg/m(2) with bevacizumab 15 mg/kg on day 1 of a 21-day cycle. The primary endpoint was progression-free survival (PFS). Secondary endpoints included response rate (RR) and overall survival (OS). Neuropilin-1 (NRP1) and -2 (NRP2) mRNA expression was evaluated in archived tumor. RESULTS: Thirty-five patients were evaluable for efficacy. Median PFS was 7.2 months; median OS was 10.8 months. RR was estimated at 51.4%. The regimen was tolerable with expected drug class-related toxicities. NRP2 mRNA levels significantly correlated with PFS (p = 0.042) and showed a trend toward significance with OS (p = 0.051). Nonsignificant trends for NRP1 were noted for higher expression levels and worse outcome. CONCLUSIONS: Bevacizumab can be given safely with chemotherapy in patients with metastatic esophagogastric adenocarcinomas. The combination of capecitabine, oxaliplatin, plus bevacizumab has activity comparable to other bevacizumab-containing regimens in metastatic gastroesophageal cancer.
Authors
Uronis, HE; Bendell, JC; Altomare, I; Blobe, GC; Hsu, SD; Morse, MA; Pang, H; Zafar, SY; Conkling, P; Favaro, J; Arrowood, CC; Cushman, SM; Meadows, KL; Brady, JC; Nixon, AB; Hurwitz, HI
MLA Citation
Uronis, Hope E., et al. “A phase II study of capecitabine, oxaliplatin, and bevacizumab in the treatment of metastatic esophagogastric adenocarcinomas.Oncologist, vol. 18, no. 3, 2013, pp. 271–72. Pubmed, doi:10.1634/theoncologist.2012-0404.
URI
https://scholars.duke.edu/individual/pub932644
PMID
23485624
Source
pubmed
Published In
Oncologist
Volume
18
Published Date
Start Page
271
End Page
272
DOI
10.1634/theoncologist.2012-0404

Immune Cells and the Tumor Microenvironment

Authors
Hsu, DS; Morse, M; Clay, T; Devi, G; Kim Lyerly, H
MLA Citation
Hsu, D. S., et al. “Immune Cells and the Tumor Microenvironment.” Genomic and Personalized Medicine, Two-Vol Set, 2009, pp. 818–29. Scopus, doi:10.1016/B978-0-12-369420-1.00068-8.
URI
https://scholars.duke.edu/individual/pub967427
Source
scopus
Published Date
Start Page
818
End Page
829
DOI
10.1016/B978-0-12-369420-1.00068-8

Structure and function of the UvrB protein.

UvrB plays a central role in (A)BC excinuclease. To identify the regions of UvrB which are involved in interacting with UvrA, UvrC, and DNA, deletion mutants, point mutants, and various fusion forms of UvrB were constructed and characterized. We found that the region encompassing amino acid residues 115-250 of UvrB binds to UvrA, while the region encompassing amino acid residues 547-673 binds to both UvrA and UvrC. In addition, the region between these two domains, which contains the helicase motifs II-VI, was found to be involved in binding to DNA. Within this DNA-binding region, two point mutants, E265A and E338A, were found to be unable to bind DNA while two residues, Phe-365 and Phe-496, were identified to interact with DNA. Furthermore, fluorescence quenching studies with mutants F365W and F496W and repair of thymine cyclobutane dimers by photoinduced electron transfer by these mutants suggest that residues Phe-365 and Phe-496 interact with DNA most likely through stacking interactions.
Authors
Hsu, DS; Kim, ST; Sun, Q; Sancar, A
MLA Citation
Hsu, D. S., et al. “Structure and function of the UvrB protein.J Biol Chem, vol. 270, no. 14, Apr. 1995, pp. 8319–27. Pubmed, doi:10.1074/jbc.270.14.8319.
URI
https://scholars.duke.edu/individual/pub777462
PMID
7713940
Source
pubmed
Published In
The Journal of Biological Chemistry
Volume
270
Published Date
Start Page
8319
End Page
8327
DOI
10.1074/jbc.270.14.8319

Aldolase B-Mediated Fructose Metabolism Drives Metabolic Reprogramming of Colon Cancer Liver Metastasis.

Cancer metastasis accounts for the majority of cancer-related deaths and remains a clinical challenge. Metastatic cancer cells generally resemble cells of the primary cancer, but they may be influenced by the milieu of the organs they colonize. Here, we show that colorectal cancer cells undergo metabolic reprogramming after they metastasize and colonize the liver, a key metabolic organ. In particular, via GATA6, metastatic cells in the liver upregulate the enzyme aldolase B (ALDOB), which enhances fructose metabolism and provides fuel for major pathways of central carbon metabolism during tumor cell proliferation. Targeting ALDOB or reducing dietary fructose significantly reduces liver metastatic growth but has little effect on the primary tumor. Our findings suggest that metastatic cells can take advantage of reprogrammed metabolism in their new microenvironment, especially in a metabolically active organ such as the liver. Manipulation of involved pathways may affect the course of metastatic growth.
Authors
Bu, P; Chen, K-Y; Xiang, K; Johnson, C; Crown, SB; Rakhilin, N; Ai, Y; Wang, L; Xi, R; Astapova, I; Han, Y; Li, J; Barth, BB; Lu, M; Gao, Z; Mines, R; Zhang, L; Herman, M; Hsu, D; Zhang, G-F; Shen, X
MLA Citation
Bu, Pengcheng, et al. “Aldolase B-Mediated Fructose Metabolism Drives Metabolic Reprogramming of Colon Cancer Liver Metastasis.Cell Metab, vol. 27, no. 6, June 2018, pp. 1249-1262.e4. Pubmed, doi:10.1016/j.cmet.2018.04.003.
URI
https://scholars.duke.edu/individual/pub1315561
PMID
29706565
Source
pubmed
Published In
Cell Metab
Volume
27
Published Date
Start Page
1249
End Page
1262.e4
DOI
10.1016/j.cmet.2018.04.003