Scholars@Duke
Shiao-Wen David Hsu

Shiao-Wen David Hsu

Professor of Medicine
Medicine, Medical Oncology
shiaowen.hsu@duke.edu
Duke Box 3233, Durham, NC 27710
Dept of Medicine, Box 3233, Durham, NC 27710

Selected Publications

Trends in Receipt of Adjuvant Chemotherapy and its Impact on Survival in Resected Biliary Tract Cancers.

Journal Article Ann Surg Oncol · August 2023 BACKGROUND: Resection remains the cornerstone of curative-intent treatment for biliary tract cancers (BTCs). However, recent randomized data also support a role for adjuvant chemotherapy (AC). This study aimed to characterize trends in the use of AC and su ... Full text Link to item Cite

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

Journal Article Bioorg Med Chem · November 1, 2018 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 Dishev ... Full text Link to item Cite

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

Journal Article Cell Metab · June 5, 2018 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 sh ... Full text Link to item Cite

Activation of the mTOR Pathway by Oxaliplatin in the Treatment of Colorectal Cancer Liver Metastasis.

Journal Article PLoS One · 2017 BACKGROUND: Standard of care treatment for colorectal cancer liver metastasis consists of a cytotoxic chemotherapy in combination with a targeted agent. Clinical trials have guided the use of these combinatory therapies, but it remains unclear what the opt ... Full text Link to item Cite

Development of a Novel c-MET-Based CTC Detection Platform.

Journal Article Mol Cancer Res · June 2016 UNLABELLED: Amplification of the MET oncogene is associated with poor prognosis, metastatic dissemination, and drug resistance in many malignancies. We developed a method to capture and characterize circulating tumor cells (CTC) expressing c-MET using a fe ... Full text Open Access Link to item Cite

In Vivo Selection Against Human Colorectal Cancer Xenografts Identifies an Aptamer That Targets RNA Helicase Protein DHX9.

Journal Article Mol Ther Nucleic Acids · April 26, 2016 The ability to selectively target disease-related tissues with molecules is critical to the design of effective therapeutic and diagnostic reagents. Recognizing the differences between the in vivo environment and in vitro conditions, we employed an in vivo ... Full text Link to item Cite

Cystine Deprivation Triggers Programmed Necrosis in VHL-Deficient Renal Cell Carcinomas.

Journal Article Cancer Res · April 1, 2016 Oncogenic transformation may reprogram tumor metabolism and render cancer cells addicted to extracellular nutrients. Deprivation of these nutrients may therefore represent a therapeutic opportunity, but predicting which nutrients cancer cells become addict ... Full text Link to item Cite

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

Journal Article Nat Commun · April 15, 2015 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 ... Full text Link to item Cite

Mismatch repair gone awry: Management of Lynch syndrome.

Journal Article Crit Rev Oncol Hematol · March 2015 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 t ... Full text Link to item Cite

Adjuvant chemotherapy for t1 node-positive colon cancers provides significant survival benefit.

Journal Article Dis Colon Rectum · December 2014 BACKGROUND: Contemporary treatment of node-positive (N+) colon cancer consists of adjuvant chemotherapy; however, randomized data supporting this practice were derived from lesions T2 or greater. Minimal data exist regarding the use and need for adjuvant c ... Full text Link to item Cite

Phase I study of capecitabine, oxaliplatin, bevacizumab, and everolimus in advanced solid tumors.

Journal Article Invest New Drugs · August 2014 PURPOSE: To define maximum tolerated dose (MTD), toxicities, and pharmacodynamics of capecitabine, oxaliplatin, bevacizumab, and everolimus in advanced solid tumor patients. DESIGN: This was a standard "3 + 3" dose-escalation trial. All subjects received b ... Full text Link to item Cite

The genomic landscape of mantle cell lymphoma is related to the epigenetically determined chromatin state of normal B cells.

Journal Article Blood · May 8, 2014 In this study, we define the genetic landscape of mantle cell lymphoma (MCL) through exome sequencing of 56 cases of MCL. We identified recurrent mutations in ATM, CCND1, MLL2, and TP53. We further identified a number of novel genes recurrently mutated in ... Full text Link to item Cite

Phase I study of dasatinib in combination with capecitabine, oxaliplatin and bevacizumab followed by an expanded cohort in previously untreated metastatic colorectal cancer.

Journal Article Invest New Drugs · April 2014 PURPOSE: Dasatinib inhibits src family kinases and has anti-angiogenic properties. We conducted a phase I study of dasatinib, capecitabine, oxaliplatin, and bevacizumab (CapeOx/bevacizumab), with an expansion cohort in metastatic colorectal cancer (CRC). M ... Full text Link to item Cite

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.

Journal Article Ann Surg · December 2013 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: Rec ... Full text Link to item Cite

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

Journal Article Cancer Immunol Immunother · August 2013 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 ... Full text Link to item Cite

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

Journal Article J Surg Oncol · March 2013 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 ab ... Full text Link to item Cite

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

Journal Article Oncologist · 2013 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 capec ... Full text Link to item Cite

Use of molecular biomarkers to inform adjuvant therapy for colon cancer

Journal Article ONCOLOGY (United States) · January 1, 2013 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 ... Cite

Characterization of an oxaliplatin sensitivity predictor in a preclinical murine model of colorectal cancer.

Journal Article Mol Cancer Ther · July 2012 Despite advances in contemporary chemotherapeutic strategies, long-term survival still remains elusive for patients with metastatic colorectal cancer. A better understanding of the molecular markers of drug sensitivity to match therapy with patient is need ... Full text Link to item Cite

Gene expression profiling of peritoneal metastases from appendiceal and colon cancer demonstrates unique biologic signatures and predicts patient outcomes.

Journal Article J Am Coll Surg · April 2012 BACKGROUND: Treatment of peritoneal metastases from appendiceal and colon cancer with cytoreductive surgery and hyperthermic intraperitoneal chemotherapy (HIPEC) shows great promise. Although long-term disease-free survival is achieved in some cases with t ... Full text Link to item Cite

Histological and molecular evaluation of patient-derived colorectal cancer explants.

Journal Article PLoS One · 2012 Mouse models have been developed to investigate colorectal cancer etiology and evaluate new anti-cancer therapies. While genetically engineered and carcinogen-induced mouse models have provided important information with regard to the mechanisms underlying ... Full text Link to item Cite

Predictive and prognostic biomarkers in colorectal cancer

Journal Article Frontiers in Biology · December 1, 2011 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 curati ... Full text Cite

A methodology for utilization of predictive genomic signatures in FFPE samples.

Journal Article BMC Med Genomics · July 11, 2011 BACKGROUND: Gene expression signatures developed to measure the activity of oncogenic signaling pathways have been used to dissect the heterogeneity of tumor samples and to predict sensitivity to various cancer drugs that target components of the relevant ... Full text Link to item Cite

Antihelminth compound niclosamide downregulates Wnt signaling and elicits antitumor responses in tumors with activating APC mutations.

Journal Article Cancer Res · June 15, 2011 Wnt/β-catenin pathway activation caused by adenomatous polyposis coli (APC) mutations occurs in approximately 80% of sporadic colorectal cancers (CRC). The antihelminth compound niclosamide downregulates components of the Wnt pathway, specifically Dishevel ... Full text Link to item Cite

A phase II trial of bevacizumab plus everolimus for patients with refractory metastatic colorectal cancer.

Journal Article Oncologist · 2011 PURPOSE: For patients with metastatic colorectal cancer (mCRC), no standard therapy exists after progression on 5-fluorouracil, oxaliplatin, irinotecan, bevacizumab, and cetuximab or panitumumab. Preclinical data demonstrated that combined vascular endothe ... Full text Link to item Cite

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

Journal Article J Natl Cancer Inst · October 6, 2010 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) ... Full text Link to item Cite

Immune signatures predict prognosis in localized cancer.

Journal Article Cancer Invest · August 2010 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 express ... Full text Link to item Cite

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.

Journal Article Br J Cancer · January 5, 2010 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 ca ... Full text Link to item Cite

MYC activity mitigates response to rapamycin in prostate cancer through eukaryotic initiation factor 4E-binding protein 1-mediated inhibition of autophagy.

Journal Article Cancer Res · October 1, 2009 Loss of PTEN and activation of phosphoinositide 3-kinase are commonly observed in advanced prostate cancer. Inhibition of mammalian target of rapamycin (mTOR), a downstream target of phosphoinositide 3-kinase signaling, results in cell cycle arrest and apo ... Full text Open Access Link to item Cite

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

Journal Article Proc Natl Acad Sci U S A · March 31, 2009 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 tra ... Full text Link to item Cite

A genomic approach to colon cancer risk stratification yields biologic insights into therapeutic opportunities.

Journal Article Proc Natl Acad Sci U S A · December 9, 2008 Gene expression profiles provide an opportunity to dissect the heterogeneity of solid tumors, including colon cancer, to improve prognosis and predict response to therapies. Bayesian binary regression methods were used to generate a signature of disease re ... Full text Link to item Cite

A genomic approach to identify molecular pathways associated with chemotherapy resistance.

Journal Article Mol Cancer Ther · October 2008 Resistance to chemotherapy in cancer is common. As gene expression profiling has been shown to anticipate chemotherapeutic resistance, we sought to identify cellular pathways associated with resistance to facilitate effective combination therapy. Gene set ... Full text Link to item Cite

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

Journal Article J Clin Oncol · July 10, 2008 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, m ... Full text Link to item Cite

Gene expression signatures, clinicopathological features, and individualized therapy in breast cancer.

Journal Article JAMA · April 2, 2008 CONTEXT: Gene expression profiling may be useful for prognostic and therapeutic strategies in breast carcinoma. OBJECTIVES: To demonstrate the value in integrating genomic information with clinical and pathological risk factors, to refine prognosis, and to ... Full text Link to item Cite

Age-specific differences in oncogenic pathway deregulation seen in human breast tumors.

Journal Article PLoS One · January 2, 2008 PURPOSE: To define the biology driving the aggressive nature of breast cancer arising in young women. EXPERIMENTAL DESIGN: Among 784 patients with early stage breast cancer, using prospectively-defined, age-specific cohorts (young or=6 ... Full text Open Access Link to item Cite

Pharmacogenomic strategies provide a rational approach to the treatment of cisplatin-resistant patients with advanced cancer.

Journal Article J Clin Oncol · October 1, 2007 PURPOSE: Standard treatment for advanced non-small-cell lung cancer (NSCLC) includes the use of a platinum-based chemotherapy regimen. However, response rates are highly variable. Newer agents, such as pemetrexed, have shown significant activity as second- ... Full text Link to item Cite

Role of mouse cryptochrome blue-light photoreceptor in circadian photoresponses.

Journal Article Science · November 20, 1998 Cryptochromes are photoactive pigments in the eye that have been proposed to function as circadian photopigments. Mice lacking the cryptochrome 2 blue-light photoreceptor gene (mCry2) were tested for circadian clock-related functions. The mutant mice had a ... Full text Link to item Cite

Reaction mechanism of (6-4) photolyase.

Journal Article J Biol Chem · December 19, 1997 The (6-4) photolyase catalyzes the photoreversal of the (6-4) dipyrimidine photoproducts induced in DNA by ultraviolet light. Using the cloned Drosophila melanogaster (6-4) photolyase gene, we overproduced and purified the recombinant enzyme. The binding a ... Full text Link to item Cite

Characterization of reaction intermediates of human excision repair nuclease.

Journal Article J Biol Chem · November 14, 1997 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 adopte ... Full text Link to item Cite

Putative human blue-light photoreceptors hCRY1 and hCRY2 are flavoproteins.

Journal Article Biochemistry · November 5, 1996 Recently, a human cDNA clone with high sequence homology to the photolyase/blue-light photoreceptor family was identified. The putative protein encoded by this gene exhibited a strikingly high (48% identity) degree of homology to the Drosophila melanogaste ... Full text Link to item Cite

Reaction mechanism of human DNA repair excision nuclease.

Journal Article J Biol Chem · April 5, 1996 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 t ... Full text Link to item Cite

The other function of DNA photolyase: stimulation of excision repair of chemical damage to DNA.

Journal Article Biochemistry · December 12, 1995 DNA photolyase is a light-dependent DNA repair enzyme. It binds to cyclobutane pyrimidine dimers in DNA and upon excitation with a blue light photon splits the cyclobutane ring and restores the pyrimidines to native forms. The enzyme is specific f ... Full text Link to item Cite

Structure and function of the UvrB protein.

Journal Article J Biol Chem · April 7, 1995 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 ... Full text Link to item Cite

Reconstitution of human DNA repair excision nuclease in a highly defined system.

Journal Article J Biol Chem · February 10, 1995 Xeroderma pigmentosum is a hereditary disease caused by defective DNA repair. Somatic cell genetics and biochemical studies with cell-free extracts indicate that at least 16 polypeptides are required to carry out the repair reaction proper, i.e. the remova ... Full text Link to item Cite

Substrate spectrum of human excinuclease: repair of abasic sites, methylated bases, mismatches, and bulky adducts.

Journal Article Proc Natl Acad Sci U S A · December 6, 1994 Nucleotide-excision repair is the repair system for removing bulky lesions from DNA. Humans deficient in this repair pathway suffer from xeroderma pigmentosum (XP), a disease characterized by photodermatoses, including skin cancers. At the cellular level, ... Full text Link to item Cite

Flow linear dichroism and electron microscopic analysis of protein-DNA complexes of a mutant UvrB protein that binds to but cannot kink DNA.

Journal Article J Mol Biol · September 2, 1994 (A)BC excinuclease of Escherichia coli is the enzymatic activity resulting from sequential and partially overlapping actions of UvrA, UvrB, and UvrC protein. UvrA is a molecular matchmaker which promotes the formation of a stable UvrB-damaged DNA complex i ... Full text Link to item Cite