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:

A randomized phase II study of immunization with dendritic cells modified with poxvectors encoding CEA and MUC1 compared with the same poxvectors plus GM-CSF for resected metastatic colorectal cancer.

OBJECTIVE: To determine whether 1 of 2 vaccines based on dendritic cells (DCs) and poxvectors encoding CEA (carcinoembryonic antigen) and MUC1 (PANVAC) would lengthen survival in patients with resected metastases of colorectal cancer (CRC). BACKGROUND: Recurrences after complete resections of metastatic CRC remain frequent. Immune responses to CRC are associated with fewer recurrences, suggesting a role for cancer vaccines as adjuvant therapy. Both DCs and poxvectors are potent stimulators of immune responses against cancer antigens. METHODS: Patients, disease-free after CRC metastasectomy and perioperative chemotherapy (n = 74), were randomized to injections of autologous DCs modified with PANVAC (DC/PANVAC) or PANVAC with per injection GM-CSF (granulocyte-macrophage colony-stimulating factor). Endpoints were recurrence-free survival overall survival, and rate of CEA-specific immune responses. Clinical outcome was compared with that of an unvaccinated, contemporary group of patients who had undergone CRC metastasectomy, received similar perioperative therapy, and would have otherwise been eligible for the study. RESULTS: Recurrence-free survival at 2 years was similar (47% and 55% for DC/PANVAC and PANVAC/GM-CSF, respectively) (χ P = 0.48). At a median follow-up of 35.7 months, there were 2 of 37 deaths in the DC/PANVAC arm and 5 of 37 deaths in the PANVAC/GM-CSF arm. The rate and magnitude of T-cell responses against CEA was statistically similar between study arms. As a group, vaccinated patients had superior survival compared with the contemporary unvaccinated group. CONCLUSIONS: Both DC and poxvector vaccines have similar activity. Survival was longer for vaccinated patients than for a contemporary unvaccinated group, suggesting that a randomized trial of poxvector vaccinations compared with standard follow-up after metastasectomy is warranted. (NCT00103142).
Authors
Morse, MA; Niedzwiecki, D; Marshall, JL; Garrett, C; Chang, DZ; Aklilu, M; Crocenzi, TS; Cole, DJ; Dessureault, S; Hobeika, AC; Osada, T; Onaitis, M; Clary, BM; Hsu, D; Devi, GR; Bulusu, A; Annechiarico, RP; Chadaram, V; Clay, TM; Lyerly, HK
MLA Citation
URI
https://scholars.duke.edu/individual/pub947922
PMID
23657083
Source
pubmed
Published In
Ann Surg
Volume
258
Published Date
Start Page
879
End Page
886
DOI
10.1097/SLA.0b013e318292919e

Retraction. Pharmacogenomic strategies provide a rational approach to the treatment of cisplatin-resistant patients with advanced cancer. J Clin Oncol 25:4350–7, 2007.

URI
https://scholars.duke.edu/individual/pub769523
PMID
21148129
Source
pubmed
Published In
Journal of Clinical Oncology
Volume
28
Published Date
Start Page
5229
DOI
10.1200/JCO.2010.33.7311

Characterization of reaction intermediates of human excision repair nuclease.

Nucleotide excision repair in humans is a complex reaction involving 14 polypeptides in six repair factors for dual incisions on either sides of a DNA lesion. To identify the reaction intermediates that form by the human excision repair nuclease, we adopted three approaches: purification of functional DNA.protein complexes, permanganate footprinting, and the employment as substrate of presumptive DNA reaction intermediates containing unwound sequences 5' to, 3' to, or encompassing the DNA lesion. The first detectable reaction intermediate was formed by substrate binding of XPA, RPA, XPC.HHR23B plus TFIIH (preincision complex 1, PIC1). In this complex the DNA was unwound on either side of the lesion by no more than 10 bases. Independent of the XPG nuclease function, the XPG protein stabilized this complex, forming a long lived preincision complex 2 (PIC2). The XPF.ERCC1 complex bound to PIC2, forming PIC3, which led to dual incisions and the release of the excised oligomer. With partially unwound DNAs, thymine cyclobutane dimer was excised at a fast rate independent of XPC.HHR23B, indicating that a major function of this protein is to stabilize the unwound DNA or to aid lesion unwinding in preincision complexes.
Authors
Mu, D; Wakasugi, M; Hsu, DS; Sancar, A
MLA Citation
Mu, D., et al. “Characterization of reaction intermediates of human excision repair nuclease..” J Biol Chem, vol. 272, no. 46, Nov. 1997, pp. 28971–79. Pubmed, doi:10.1074/jbc.272.46.28971.
URI
https://scholars.duke.edu/individual/pub777459
PMID
9360969
Source
pubmed
Published In
The Journal of Biological Chemistry
Volume
272
Published Date
Start Page
28971
End Page
28979
DOI
10.1074/jbc.272.46.28971

Novel adenoviral vector induces T-cell responses despite anti-adenoviral neutralizing antibodies in colorectal cancer patients.

First-generation, E1-deleted adenovirus subtype 5 (Ad5)-based vectors, although promising platforms for use as cancer vaccines, are impeded in activity by naturally occurring or induced Ad-specific neutralizing antibodies. Ad5-based vectors with deletions of the E1 and the E2b regions (Ad5 [E1-, E2b-]), the latter encoding the DNA polymerase and the pre-terminal protein, by virtue of diminished late phase viral protein expression, were hypothesized to avoid immunological clearance and induce more potent immune responses against the encoded tumor antigen transgene in Ad-immune hosts. Indeed, multiple homologous immunizations with Ad5 [E1-, E2b-]-CEA(6D), encoding the tumor antigen carcinoembryonic antigen (CEA), induced CEA-specific cell-mediated immune (CMI) responses with antitumor activity in mice despite the presence of preexisting or induced Ad5-neutralizing antibody. In the present phase I/II study, cohorts of patients with advanced colorectal cancer were immunized with escalating doses of Ad5 [E1-, E2b-]-CEA(6D). CEA-specific CMI responses were observed despite the presence of preexisting Ad5 immunity in a majority (61.3 %) of patients. Importantly, there was minimal toxicity, and overall patient survival (48 % at 12 months) was similar regardless of preexisting Ad5 neutralizing antibody titers. The results demonstrate that, in cancer patients, the novel Ad5 [E1-, E2b-] gene delivery platform generates significant CMI responses to the tumor antigen CEA in the setting of both naturally acquired and immunization-induced Ad5-specific immunity.
Authors
Morse, MA; Chaudhry, A; Gabitzsch, ES; Hobeika, AC; Osada, T; Clay, TM; Amalfitano, A; Burnett, BK; Devi, GR; Hsu, DS; Xu, Y; Balcaitis, S; Dua, R; Nguyen, S; Balint, JP; Jones, FR; Lyerly, HK
MLA Citation
Morse, Michael A., et al. “Novel adenoviral vector induces T-cell responses despite anti-adenoviral neutralizing antibodies in colorectal cancer patients..” Cancer Immunol Immunother, vol. 62, no. 8, Aug. 2013, pp. 1293–301. Pubmed, doi:10.1007/s00262-013-1400-3.
URI
https://scholars.duke.edu/individual/pub941182
PMID
23624851
Source
pubmed
Published In
Cancer Immunol Immunother
Volume
62
Published Date
Start Page
1293
End Page
1301
DOI
10.1007/s00262-013-1400-3

CSPG4 protein as a new target for the antibody-based immunotherapy of triple-negative breast cancer.

BACKGROUND: The cell surface proteoglycan, chondroitin sulfate proteoglycan 4 (CSPG4), is a potential target for monoclonal antibody (mAb)-based immunotherapy for many types of cancer. The lack of effective therapy for triple-negative breast cancer (TNBC) prompted us to examine whether CSPG4 is expressed in TNBC and can be targeted with CSPG4-specific mAb. METHODS: CSPG4 protein expression was assessed in 44 primary TNBC lesions, in TNBC cell lines HS578T, MDA-MB-231, MDA-MB-435, and SUM149, and in tumor cells in pleural effusions from 12 metastatic breast cancer patients. The effect of CSPG4-specific mAb 225.28 on growth, adhesion, and migration of TNBC cells was tested in vitro. The ability of mAb 225.28 to induce regression of tumor metastases (n = 7 mice) and to inhibit spontaneous metastasis and tumor recurrence (n = 12 mice per group) was tested in breast cancer models in mice. The mechanisms responsible for the antitumor effect of mAb 225.28 were also investigated in the cell lines and in the mouse models. All statistical tests were two-sided. RESULTS: CSPG4 protein was preferentially expressed in 32 of the 44 (72.7%) primary TNBC lesions tested, in TNBC cell lines, and in tumor cells in pleural effusions from 12 metastatic breast cancer patients. CSPG4-specific mAb 225.28 statistically significantly inhibited growth, adhesion, and migration of TNBC cells in vitro. mAb 225.28 induced 73.1% regression of tumor metastasis in a TNBC cell-derived experimental lung metastasis model (mAb 225.28 vs control, mean area of metastatic nodules = 44590.8 vs 165950.8 μm(2); difference of mean = 121360.0 μm(2), 95% confidence interval = 91010.7 to 151709.4 μm(2); P < .001). Additionally, mAb 225.28 statistically significantly reduced spontaneous lung metastases and tumor recurrences in an orthotopic xenograft mouse model. The mechanisms responsible for antitumor effect included increased apoptosis and reduced mitotic activity in tumor cells, decreased blood vessel density in the tumor microenvironment, and reduced activation of signaling pathways involved in cell survival, proliferation and metastasis. CONCLUSIONS: This study identified CSPG4 as a new target for TNBC. The antitumor activity of CSPG4-specific mAb was mediated by multiple mechanisms, including the inhibition of signaling pathways crucial for TNBC cell survival, proliferation, and metastasis.
Authors
Wang, X; Osada, T; Wang, Y; Yu, L; Sakakura, K; Katayama, A; McCarthy, JB; Brufsky, A; Chivukula, M; Khoury, T; Hsu, DS; Barry, WT; Lyerly, HK; Clay, TM; Ferrone, S
MLA Citation
Wang, Xinhui, et al. “CSPG4 protein as a new target for the antibody-based immunotherapy of triple-negative breast cancer..” J Natl Cancer Inst, vol. 102, no. 19, Oct. 2010, pp. 1496–512. Pubmed, doi:10.1093/jnci/djq343.
URI
https://scholars.duke.edu/individual/pub777456
PMID
20852124
Source
pubmed
Published In
J Natl Cancer Inst
Volume
102
Published Date
Start Page
1496
End Page
1512
DOI
10.1093/jnci/djq343