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:

Modest advances in survival for patients with colorectal-associated peritoneal carcinomatosis in the era of modern chemotherapy.

BACKGROUND: The treatment of metastatic colorectal cancer (CRC) has evolved rapidly over the last decade, with combination chemotherapy and targeted biologic agents leading to significant improvements in survival. Despite these advances, little is known about their effectiveness in CRC-associated peritoneal carcinomatosis. The purpose of this study was to evaluate outcomes in patients with CRC-associated PC treated in the era of modern chemotherapy. METHODS: We retrospectively reviewed an institutional tumor database from 1996 to 2008. Survival data were evaluated for patients treated with PC before and after 2003. No patients before 2003 were treated with combination chemotherapy or biologic therapy. The modern chemotherapy group consisted of patients treated after 2003. Survival curves were estimated. RESULTS: Overall, 173 patients were identified. Median follow-up was 8.6 months. Median survival in the historic group (n = 91) was 8.9 months and 16.3 months in the modern chemotherapy group (n = 82) (P < 0.004). Age was the only significant covariate. The survival difference between the modern chemotherapy cohort and control cohort persisted after adjustment for age. In a subset of patients in the modern chemotherapy era group, for which treatment regimen could be definitively identified, survival was even greater-23.8 months. CONCLUSIONS: Patients with CRC-associated PC treated with modern combination chemotherapy and biologic therapy have a significantly longer median survival compared to our historical cohort. Despite these improvements, outcomes still remain poor. Therapeutic adjuncts such as surgical cytoreduction and hyperthermic intraperitoneal chemotherapy (HIPEC) in appropriately selected patients remain promising options to improve outcomes for patients with peritoneal-based disease.
Authors
Zani, S; Papalezova, K; Stinnett, S; Tyler, D; Hsu, D; Blazer, DG
MLA Citation
Zani, Sabino, et al. “Modest advances in survival for patients with colorectal-associated peritoneal carcinomatosis in the era of modern chemotherapy.J Surg Oncol, vol. 107, no. 4, Mar. 2013, pp. 307–11. Pubmed, doi:10.1002/jso.23222.
URI
https://scholars.duke.edu/individual/pub761002
PMID
22811275
Source
pubmed
Published In
J Surg Oncol
Volume
107
Published Date
Start Page
307
End Page
311
DOI
10.1002/jso.23222

Immune signatures predict prognosis in localized cancer.

The host immune response can impact cancer growth, prognosis, and response to therapy. In colorectal cancer, the presence of cells involved with T-cell-mediated adaptive immunity predicts survival better than the current staging method. We used the expression of genes recently associated with host immune responses (T(H1)-mediated adaptive immunity, inflammation, and immune suppression) to perform hierarchical clustering of multiple large cohorts of cancer specimens to determine if immune-related gene expression resulted in clinical significant groupings of tumors. Microarray data from prostate cancer (n = 79), breast cancer (n = 132), lung cancer (n = 84), glioblastoma multiforme (n = 120), and lymphoma (n = 127) were analyzed. Among adenocarcinomas, the T(H1)-mediated adaptive immunity genes were consistently associated with better prognosis, while genes associated with inflammation and immune suppression were variably associated with outcome. Specifically, increased expression of the T(H1)-mediated adaptive immunity genes was associated with good prognosis in breast cancer patients under 45 years of age (p = .04, hazard ratio [HR] = 0.42) and in prostate cancer patients (p = .03, HR = 0.36) but not in lung cancer patients (p = 0.45, HR = 1.37). In lymphoma, patients with increased expression of inflammation and immune suppression genes had better prognosis than those expressing the T(H1)-mediated adaptive immunity genes (p = .01, HR = 0.43) and in glioblastoma multiforme, the expression of inflammation genes conferred improved prognosis than those expressing immune suppression genes (p = 0.05, HR = 0.62). In aggregate, the gene expression signatures implicating specific components of the immune response hold prognostic import across solid tumors.
Authors
Hsu, DS; Kim, MK; Balakumaran, BS; Acharya, CR; Anders, CK; Clay, T; Lyerly, HK; Drake, CG; Morse, MA; Febbo, PG
MLA Citation
Hsu, David S., et al. “Immune signatures predict prognosis in localized cancer.Cancer Invest, vol. 28, no. 7, Aug. 2010, pp. 765–73. Pubmed, doi:10.3109/07357900903095755.
URI
https://scholars.duke.edu/individual/pub726566
PMID
20569070
Source
pubmed
Published In
Cancer Invest
Volume
28
Published Date
Start Page
765
End Page
773
DOI
10.3109/07357900903095755

Reaction mechanism of human DNA repair excision nuclease.

Nucleotide excision repair consists of removal of the damaged nucleotide(s) from DNA by dual incision of the damaged strand on both sides of the lesion, followed by filling of the resulting gap and ligation. In humans, 14-16 polypeptides are required for the dual incision step. We have purified the required proteins to homogeneity and reconstituted the dual incision activity (excision nuclease) in a defined enzyme/substrate system. The system was highly efficient, removing >30% of the thymine dimers under optimal conditions. All of the six fractions that constitute the excision nuclease were required for dual incision of the thymine dimer substrate. However, when a cholesterol-substituted oligonucleotide was used as substrate, excision occurred in the absence of the XPC-HHR23B complex, reminiscent of transcription-coupled repair in the XP-C mutant cell line. Replication protein A is absolutely required for both incisions. The XPG subunit is essential to the formation of the preincision complex, but the repair complex can assemble and produce normal levels of 3'-incision in the absence of XPF-ERCC1. Kinetic experiments revealed that the 3'-incision precedes the 5'-incision. Consistent with the kinetic data, uncoupled 5'-incision was never observed in the reconstituted system. Two forms of TFIIH were used in the reconstitution reaction, one containing the CDK7-cyclin H pair and one lacking it. Both forms were equally active in excision. The excised oligomer dissociated from the gapped DNA in a nucleoprotein complex. In total, these results provide a detailed account of the reactions occurring during damage removal by human excision nuclease.
Authors
Mu, D; Hsu, DS; Sancar, A
MLA Citation
Mu, D., et al. “Reaction mechanism of human DNA repair excision nuclease.J Biol Chem, vol. 271, no. 14, Apr. 1996, pp. 8285–94. Pubmed, doi:10.1074/jbc.271.14.8285.
URI
https://scholars.duke.edu/individual/pub777460
PMID
8626523
Source
pubmed
Published In
The Journal of Biological Chemistry
Volume
271
Published Date
Start Page
8285
End Page
8294
DOI
10.1074/jbc.271.14.8285

Use of molecular biomarkers to inform adjuvant therapy for colon cancer

The decision about who may derive benefit from adjuvant chemotherapy in colon cancer is often a difficult one for clinicians. While multiple trials have demonstrated that adjuvant chemotherapy reduces the risk of recurrence and improves overall survival in patients with stage III disease, the data supporting the use of adjuvant chemotherapy in patients with stage II disease are not as compelling. Because adjuvant therapy can have significant toxicity, tools to help clinicians determine who may derive a benefit from therapy are of the utmost importance. Recent advances in high throughput technologies have led to the identification of molecular biomarkers-including microsatellite instability (MSI), loss of heterozygosity (LOH), p53, Kirsten rat sarcoma viral oncogene homolog (KRAS), v-raf murine sarcoma viral oncogene homolog B1 (BRAF), thymidylate synthase (TS), and excision repair cross-complementation group 1 (ERCC1)-as well as various multigene assays that are being studied for their ability to offer both prognostic and predictive information to clinicians. Here we review the current knowledge about molecular biomarkers that may aid the clinician in offering personalized cancer therapy based on the genetic landscape of an individual patient's tumor.
Authors
Mettu, NB; Hurwitz, H; Hsu, DS
MLA Citation
Mettu, N. B., et al. “Use of molecular biomarkers to inform adjuvant therapy for colon cancer.” Oncology (United States), vol. 27, no. 8, Jan. 2013.
URI
https://scholars.duke.edu/individual/pub962151
Source
scopus
Published In
Oncology (Williston Park, N.Y.)
Volume
27
Published Date

Metastatic colorectal cancer cells from patients previously treated with chemotherapy are sensitive to T-cell killing mediated by CEA/CD3-bispecific T-cell-engaging BiTE antibody.

BACKGROUND: Novel technologies to redirect T-cell killing against cancer cells are emerging. We hypothesised that metastatic human colorectal cancer (CRC) previously treated with conventional chemotherapy would be sensitive to T-cell killing mediated by carcinoembryonic antigen (CEA)/CD3-bispecific T-cell-engaging BiTE antibody (MEDI-565). METHODS: We analysed proliferation and lysis of CEA-positive (CEA+) CRC specimens that had survived previous systemic chemotherapy and biologic therapy to determine whether they could be killed by patient T cells engaged by MEDI-565 in vitro. RESULTS: At low concentrations (0.1-1 ng ml(-1)), MEDI-565+ T cells caused reduced proliferation and enhanced apoptosis of CEA+ human CRC specimens. High levels of soluble CEA did not impair killing by redirected T cells and there was no increase in resistance to T-cell killing despite multiple rounds of exposure. CONCLUSIONS: This study shows for the first time that metastatic CRC specimens derived from patients previously treated with conventional chemotherapy can be lysed by patient T cells. Clinical testing of cancer immunotherapies, such as MEDI-565 that result in exposure of tumours to large numbers of T cells, is warranted.
Authors
Osada, T; Hsu, D; Hammond, S; Hobeika, A; Devi, G; Clay, TM; Lyerly, HK; Morse, MA
MLA Citation
URI
https://scholars.duke.edu/individual/pub726584
PMID
19953093
Source
pubmed
Published In
Br J Cancer
Volume
102
Published Date
Start Page
124
End Page
133
DOI
10.1038/sj.bjc.6605364