Scholars@Duke
Stephanie Gaillard

Stephanie Gaillard

Adjunct Assistant Professor in the Department of Medicine
Medicine, Medical Oncology
stephanie.gaillard@duke.edu
DUMC 3079, Durham, NC 27710
DUMC Box 3079, Durham, NC 27710

Selected Publications

Dual Inhibition of SYK and EGFR Overcomes Chemoresistance by Inhibiting CDC6 and Blocking DNA Replication.

Journal Article Cancer Res · November 15, 2024 Targeting multiple signaling pathways has been proposed as a strategy to overcome resistance to single-pathway inhibition in cancer therapy. A previous study in epithelial ovarian cancers identified hyperactivity of spleen tyrosine kinase (SYK) and EGFR, w ... Full text Link to item Cite

Association of glutaminase expression with immune-suppressive tumor microenvironment, clinicopathologic features, and clinical outcomes in endometrial cancer.

Journal Article Int J Gynecol Cancer · November 4, 2024 OBJECTIVE: Increased glutamine metabolism by cancer cells via upregulation of the drug-targetable enzyme glutaminase may contribute to an immune-suppressive tumor microenvironment. Inhibiting glutamine metabolism can not only suppress tumor growth, but als ... Full text Link to item Cite

Long-term disease-free survival with chemotherapy and pembrolizumab in a patient with unmeasurable, advanced stage dedifferentiated endometrial carcinoma

Journal Article Gynecologic Oncology Reports · June 1, 2024 Dedifferentiated endometrial carcinoma is a rare, highly aggressive subtype of endometrial cancer associated with poor survival outcomes. Current guidelines recommend treatment of advanced-stage disease with surgical staging or cytoreduction and platinum/t ... Full text Cite

Pembrolizumab with bevacizumab and cyclophosphamide for the treatment of recurrent ovarian clear cell carcinoma: A case series

Journal Article Gynecologic Oncology Reports · June 1, 2024 Introduction: Treatment for recurrent ovarian clear cell carcinoma (OCCC) is clinically challenging as response rates to traditional chemotherapy are low, and recurrence rates are high. Immunotherapy has shown promise for this ovarian cancer (OC) subtype, ... Full text Cite

Niraparib, Dostarlimab, and Bevacizumab as Combination Therapy in Pretreated, Advanced Platinum-Resistant Ovarian Cancer: Findings From Cohort A of the OPAL Phase II Trial.

Journal Article JCO Precis Oncol · May 2024 PURPOSE: To report the results of OPAL (ClinicalTrials.gov identifier: NCT03574779) cohort A, a single-arm substudy of niraparib plus dostarlimab and bevacizumab for the treatment of advanced, platinum-resistant ovarian cancer (PROC). METHODS: Participants ... Full text Link to item Cite

Vulvar Cancer, Version 3.2024, NCCN Clinical Practice Guidelines in Oncology.

Journal Article J Natl Compr Canc Netw · March 2024 Vulvar cancer is annually diagnosed in an estimated 6,470 individuals and the vast majority are histologically squamous cell carcinomas. Vulvar cancer accounts for 5% to 8% of gynecologic malignancies. Known risk factors for vulvar cancer include increasin ... Full text Link to item Cite

Uterine MEIS1::NCOA2 Fusion Sarcoma With Lung Metastasis: A Case Report and Review of the Literature.

Journal Article Int J Gynecol Pathol · January 1, 2024 MEIS1::NCOA1/2 fusion sarcomas are a recently described novel entity arising in a variety of locations with a predilection for the genitourinary tract and gynecologic organs. Despite multiple locoregional recurrences, these tumors are thought to behave in ... Full text Link to item Cite

NCCN Guidelines® Insights: Cervical Cancer, Version 1.2024.

Journal Article J Natl Compr Canc Netw · December 2023 The NCCN Guidelines for Cervical Cancer provide recommendations for all aspects of management for cervical cancer, including the diagnostic workup, staging, pathology, and treatment. The guidelines also include details on histopathologic classification of ... Full text Link to item Cite

Transforming ovarian cancer care by targeting minimal residual disease.

Journal Article Med · November 10, 2023 Frontline treatment and resultant cure rates in patients with advanced ovarian cancer have changed little over the past several decades. Here, we outline a multidisciplinary approach aimed at gaining novel therapeutic insights by focusing on the poorly und ... Full text Link to item Cite

Niraparib and dostarlimab for the treatment of recurrent platinum-resistant ovarian cancer: results of a Phase II study (MOONSTONE/GOG-3032).

Journal Article Gynecol Oncol · November 2023 OBJECTIVE: This study assessed the efficacy, safety, and health-related quality of life (HRQoL) of the treatment regimen of dostarlimab, a programmed death-1 inhibitor, combined with niraparib, a poly (ADP-ribose) polymerase inhibitor, in patients with BRC ... Full text Link to item Cite

Low-grade serous ovarian cancer: expert consensus report on the state of the science.

Journal Article Int J Gynecol Cancer · September 4, 2023 Compared with high-grade serous carcinoma, low-grade serous carcinoma of the ovary or peritoneum is a less frequent epithelial ovarian cancer type that is poorly sensitive to chemotherapy and affects younger women, many of whom endure years of ineffective ... Full text Link to item Cite

Temozolomide Sensitizes ARID1A-Mutated Cancers to PARP Inhibitors.

Journal Article Cancer Res · August 15, 2023 UNLABELLED: ARID1A is a subunit of SWI/SNF chromatin remodeling complexes and is mutated in many types of human cancers, especially those derived from endometrial epithelium, including ovarian and uterine clear cell carcinoma (CCC) and endometrioid carcino ... Full text Link to item Cite

Combination ATR (ceralasertib) and PARP (olaparib) Inhibitor (CAPRI) Trial in Acquired PARP Inhibitor-Resistant Homologous Recombination-Deficient Ovarian Cancer.

Journal Article Clin Cancer Res · August 1, 2023 PURPOSE: Addition of ataxia telangiectasia and Rad3-related kinase inhibitors (ATRi) to PARP inhibitors (PARPi) overcomes PARPi resistance in high-grade serous ovarian cancer (HGSOC) cell and mouse models. We present the results of an investigator-initiate ... Full text Link to item Cite

Phase I Trial of Intravenous Mistletoe Extract in Advanced Cancer

Journal Article Cancer Research Communications · February 1, 2023 Purpose: Mistletoe extract (ME) is widely used for patients with cancer to support therapy and to improve quality of life (QoL). However, its use is controversial due to suboptimal trials and a lack of data supporting its intravenous administration. Materi ... Full text Cite

Case report: prolonged durable clinical benefit and low toxicity from combination endocrine therapy in a patient with recurrent endometrial carcinoma

Journal Article Frontiers in Oncology · January 1, 2023 Background: Endometrial carcinoma is the most common gynecologic cancer, with increasing incidence and mortality. Combination endocrine therapy comprised of tamoxifen and progestational agents has demonstrated promising results in treating recurrent diseas ... Full text Cite

Stress hormones are associated with inflammatory cytokines and attenuation of T-cell function in the ascites from patients with high grade serous ovarian cancer.

Journal Article Brain Behav Immun Health · December 2022 Mounting evidence suggests that chronic stress and subsequent distress can promote ovarian cancer progression. These altered psychological states have been linked to sustained release of stress hormones, activation of the β-adrenergic receptors in ovarian ... Full text Link to item Cite

Translational randomized phase II trial of cabozantinib in combination with nivolumab in advanced, recurrent, or metastatic endometrial cancer.

Journal Article J Immunother Cancer · March 2022 BACKGROUND: Combining immunotherapy and antiangiogenic agents is a promising treatment strategy in endometrial cancer. To date, no biomarkers for response have been identified and data on post-immunotherapy progression are lacking. We explored the combinat ... Full text Link to item Cite

Trametinib versus standard of care in patients with recurrent low-grade serous ovarian cancer (GOG 281/LOGS): an international, randomised, open-label, multicentre, phase 2/3 trial.

Journal Article Lancet · February 5, 2022 BACKGROUND: Low-grade serous carcinoma of the ovary or peritoneum is characterised by MAPK pathway aberrations and its reduced sensitivity to chemotherapy relative to high-grade serous carcinoma. We compared the MEK inhibitor trametinib to physician's choi ... Full text Link to item Cite

Development of small molecule inhibitors targeting PBX1 transcription signaling as a novel cancer therapeutic strategy

Journal Article iScience · November 19, 2021 PBX1 is a transcription factor involved in diverse cellular functions including organ development, stem cell renewal, and tumorigenesis. PBX1 is localized at chr1q23.3, a frequently amplified chromosomal region, and it is overexpressed in many human malign ... Full text Cite

A novel human endometrial epithelial cell line for modeling gynecological diseases and for drug screening.

Journal Article Lab Invest · November 2021 Endometrium-related malignancies including uterine endometrioid carcinoma, ovarian clear cell carcinoma and ovarian endometrioid carcinoma are major types of gynecologic cancer, claiming more than 13,000 women's lives annually in the United States. In vitr ... Full text Link to item Cite

Lurbinectedin versus pegylated liposomal doxorubicin or topotecan in patients with platinum-resistant ovarian cancer: A multicenter, randomized, controlled, open-label phase 3 study (CORAIL).

Journal Article Gynecologic oncology · November 2021 ObjectiveThe randomized phase 3 CORAIL trial evaluated whether lurbinectedin improved progression-free survival (PFS) compared to pegylated liposomal doxorubicin (PLD) or topotecan in patients with platinum-resistant ovarian cancer.Methods Full text Cite

Combination ATR and PARP Inhibitor (CAPRI): A phase 2 study of ceralasertib plus olaparib in patients with recurrent, platinum-resistant epithelial ovarian cancer.

Journal Article Gynecol Oncol · November 2021 OBJECTIVE: Platinum-resistant, high-grade serous ovarian cancer (HGSOC) has limited treatment options. Preclinical data suggest that poly(ADP-ribose) polymerase inhibitors (PARPi) and ataxia telangiectasia and Rad3-related kinase inhibitors (ATRi) are syne ... Full text Link to item Cite

PD-1 blockade synergizes with intratumoral vaccination of a therapeutic HPV protein vaccine and elicits regression of tumor in a preclinical model.

Journal Article Cancer Immunol Immunother · April 2021 INTRODUCTION: The human papillomavirus (HPV) encoded oncoproteins E6 and E7 are constitutively expressed in HPV-associated cancers, making them logical therapeutic targets. Intramuscular immunization of patients with HPV16 L2E7E6 fusion protein vaccine (TA ... Full text Link to item Cite

Development of DNA Vaccine Targeting E6 and E7 Proteins of Human Papillomavirus 16 (HPV16) and HPV18 for Immunotherapy in Combination with Recombinant Vaccinia Boost and PD-1 Antibody.

Journal Article mBio · January 19, 2021 Immunotherapy for cervical cancer should target high-risk human papillomavirus types 16 and 18, which cause 50% and 20% of cervical cancers, respectively. Here, we describe the construction and characterization of the pBI-11 DNA vaccine via the addition of ... Full text Link to item Cite

Inhibition of the MYC-Regulated Glutaminase Metabolic Axis Is an Effective Synthetic Lethal Approach for Treating Chemoresistant Ovarian Cancers.

Journal Article Cancer Res · October 15, 2020 Amplification and overexpression of the MYC oncogene in tumor cells, including ovarian cancer cells, correlates with poor responses to chemotherapy. As MYC is not directly targetable, we have analyzed molecular pathways downstream of MYC to identify potent ... Full text Link to item Cite

Molecular Classification and Emerging Targeted Therapy in Endometrial Cancer.

Journal Article Int J Gynecol Pathol · January 2020 Recent advances in molecular studies, especially genome-wide analyses, have revealed the landscape of genomic alterations present in endometrial carcinomas, and have provided valuable insight into the pathogenesis of this disease. The current challenges ar ... Full text Link to item Cite

Loss of ARID1A in Tumor Cells Renders Selective Vulnerability to Combined Ionizing Radiation and PARP Inhibitor Therapy.

Journal Article Clin Cancer Res · September 15, 2019 PURPOSE: Somatic inactivating mutations in ARID1A, a component of the SWI/SNF chromatin remodeling complex, are detected in various types of human malignancies. Loss of ARID1A compromises DNA damage repair. The induced DNA damage burden may increase relian ... Full text Link to item Cite

Spleen tyrosine kinase activity regulates epidermal growth factor receptor signaling pathway in ovarian cancer.

Journal Article EBioMedicine · September 2019 BACKGROUND: Spleen tyrosine kinase (SYK) is frequently upregulated in recurrent ovarian carcinomas, for which effective therapy is urgently needed. SYK phosphorylates several substrates, but their translational implications remain unclear. Here, we show th ... Full text Link to item Cite

A phase 1 trial of the oral DNA methyltransferase inhibitor CC-486 and the histone deacetylase inhibitor romidepsin in advanced solid tumors.

Journal Article Cancer · August 15, 2019 BACKGROUND: Epigenetic abnormalities are manifold in all solid tumors and include changes in chromatin configuration and DNA methylation. The authors designed a phase 1 study to evaluate the oral DNA methyltransferase inhibitor CC-486 combined with the his ... Full text Link to item Cite

Constitutively active ESR1 mutations in gynecologic malignancies and clinical response to estrogen-receptor directed therapies.

Journal Article Gynecol Oncol · July 2019 OBJECTIVE: Endocrine therapy is often considered as a treatment for hormone-responsive gynecologic malignancies. In breast cancer, activating mutations in the estrogen receptor (mutESR1) contribute to therapeutic resistance to endocrine therapy, especially ... Full text Link to item Cite

T cell-inflamed phenotype and increased Foxp3 expression in infiltrating T-cells of mismatch-repair deficient endometrial cancers.

Journal Article Mod Pathol · April 2019 Mismatch repair-deficient endometrial cancers have a high somatic mutation burden, suggesting that patients with these tumors may benefit from immunotherapy. Elucidating the immune suppressive mechanisms of mismatch repair-deficient endometrial cancers is ... Full text Link to item Cite

Phase III trial of lurbinectedin versus PLD or topotecan in platinum-resistant ovarian cancer patients: Results of CORAIL trial

Journal Article Annals of oncology : official journal of the European Society for Medical Oncology · October 1, 2018 Full text Cite

Inhibition of ovarian tumor cell invasiveness by targeting SYK in the tyrosine kinase signaling pathway.

Journal Article Oncogene · July 2018 Cell motility and invasiveness are prerequisites for dissemination, and largely account for cancer mortality. We have identified an actionable kinase, spleen tyrosine kinase (SYK), which is keenly tightly associated with tumor progression in ovarian cancer ... Full text Link to item Cite

Data-Derived Treatment Duration Goal for Cervical Cancer: Should 8 Weeks Remain the Target in the Era of Concurrent Chemoradiation?

Journal Article JCO Clin Cancer Inform · November 2017 PURPOSE: Prior studies have demonstrated the importance of treatment duration (TD) in radiation therapy (RT) for cervical cancer, with an 8-week goal based primarily on RT alone. This study uses a contemporary cohort to estimate the time point by which com ... Full text Link to item Cite

Primary cytoreductive surgery and adjuvant hormonal monotherapy in women with advanced low-grade serous ovarian carcinoma: Reducing overtreatment without compromising survival?

Journal Article Gynecol Oncol · October 2017 OBJECTIVES: Women with advanced-stage, low-grade serous ovarian carcinoma (LGSC) have low chemotherapy response rates and poor overall survival. Most LGSC tumors overexpress hormone receptors, which represent a potential treatment target. Our study objecti ... Full text Link to item Cite

A phase II evaluation of brivanib in the treatment of persistent or recurrent carcinoma of the cervix: An NRG Oncology/Gynecologic Oncology Group study.

Journal Article Gynecol Oncol · September 2017 BACKGROUND: Brivanib is an oral, tyrosine kinase inhibitor against vascular endothelial growth factor (VEGF) and fibroblast growth factor receptor (FGFR). We studied its efficacy and tolerability in persistent or recurrent cervical cancer patients. METHODS ... Full text Link to item Cite

Impact of Chemotherapy and Radiotherapy on Management of Early Stage Clear Cell and Papillary Serous Carcinoma of the Uterus.

Journal Article Int J Gynecol Cancer · May 2017 OBJECTIVE: The aim of the study was to assess interaction of lymph node dissection (LND), adjuvant chemotherapy (CT), and radiotherapy (RT) in stage I uterine papillary serous carcinoma (UPSC) and uterine clear cell carcinoma (UCC). METHODS/MATERIALS: The ... Full text Link to item Cite

The role of immune checkpoint inhibition in the treatment of ovarian cancer.

Journal Article Gynecol Oncol Res Pract · 2016 The introduction of immune checkpoint inhibitors has revolutionized treatment of multiple cancers and has bolstered interest in this treatment approach. So far, emerging clinical data show limited clinical efficacy of these agents in ovarian cancer with ob ... Full text Link to item Cite

Inhibition of Spleen Tyrosine Kinase Potentiates Paclitaxel-Induced Cytotoxicity in Ovarian Cancer Cells by Stabilizing Microtubules.

Journal Article Cancer Cell · July 13, 2015 Resistance to chemotherapy represents a major obstacle for long-term remission, and effective strategies to overcome drug resistance would have significant clinical impact. We report that recurrent ovarian carcinomas after paclitaxel/carboplatin treatment ... Full text Link to item Cite

Patient preferences in advanced or recurrent ovarian cancer.

Journal Article Cancer · December 1, 2014 BACKGROUND: The objective of this study was to elucidate relative preferences of women with ovarian cancer for symptoms, treatment-related side effects, and progression-free survival (PFS) relevant to choosing a treatment regimen. METHODS: Women with advan ... Full text Link to item Cite

Biology and genetics

Chapter · November 11, 2014 Cite

A phase II evaluation of AMG 102 (rilotumumab) in the treatment of persistent or recurrent epithelial ovarian, fallopian tube or primary peritoneal carcinoma: a Gynecologic Oncology Group study.

Journal Article Gynecol Oncol · March 2014 OBJECTIVE: This open-label, multi-institutional phase II trial evaluated activity and safety of rilotumumab (AMG 102), a monoclonal antibody that targets HGF (hepatocyte growth factor), the ligand for the MET receptor, in women with recurrent or persistent ... Full text Link to item Cite

Sustained elite suppression of replication competent HIV-1 in a patient treated with rituximab based chemotherapy.

Journal Article J Clin Virol · July 2011 The mechanism of elite control of HIV-1 replication is not fully understood. While immunosuppression due to rituximab based chemotherapy has been associated with increased replication of HBV, CMV, and HIV-1, control of replication-competent HIV-1 was maint ... Full text Link to item Cite

Aromatase inhibitor-associated bone and musculoskeletal effects: new evidence defining etiology and strategies for management.

Journal Article Breast Cancer Res · March 14, 2011 Aromatase inhibitors are widely used as adjuvant therapy in postmenopausal women with hormone receptor-positive breast cancer. While the agents are associated with slightly improved survival outcomes when compared to tamoxifen alone, bone and musculoskelet ... Full text Link to item Cite

Fasting-induced hepatic production of DHEA is regulated by PGC-1alpha, ERRalpha, and HNF4alpha.

Journal Article Mol Endocrinol · August 2009 Featured Publication The transcriptional coactivator peroxisome proliferator-activated receptor-gamma coactivator (PGC)-1alpha is involved in the coordinate induction of changes in gene expression in the liver that enable a homeostatic response to alterations in metabolic stat ... Full text Link to item Cite

Estrogen-related receptor alpha induces the expression of vascular endothelial growth factor in breast cancer cells.

Journal Article J Steroid Biochem Mol Biol · March 2009 Featured Publication Estrogen-related receptor alpha (ERRalpha) is an orphan member of the nuclear receptor family of transcription factors. In addition to its function as a metabolic regulator, ERRalpha has been implicated in the growth and progression of several malignancies ... Full text Link to item Cite

Definition of the molecular basis for estrogen receptor-related receptor-alpha-cofactor interactions.

Journal Article Mol Endocrinol · January 2007 Featured Publication Estrogen receptor-related receptor-alpha (ERRalpha) is an orphan nuclear receptor that does not appear to require a classical small molecule ligand to facilitate its interaction with coactivators and/or hormone response elements within target genes. Instea ... Full text Link to item Cite

Estrogen-related receptors stimulate pyruvate dehydrogenase kinase isoform 4 gene expression.

Journal Article J Biol Chem · December 29, 2006 The pyruvate dehydrogenase complex (PDC) catalyzes the conversion of pyruvate to acetyl-CoA in mitochondria and is a key regulatory enzyme in the oxidation of glucose to acetyl-CoA. Phosphorylation of PDC by the pyruvate dehydrogenase kinases (PDK2 and PDK ... Full text Link to item Cite

Receptor-selective coactivators as tools to define the biology of specific receptor-coactivator pairs.

Journal Article Mol Cell · December 8, 2006 Featured Publication In the absence of specific high-affinity agonists and antagonists, it has been difficult to define the target genes and biological responses attributable to many of the orphan nuclear receptors (ONRs). Indeed, it appears that many members of this receptor ... Full text Link to item Cite

Structure-guided synthesis of tamoxifen analogs with improved selectivity for the orphan ERRgamma.

Journal Article Bioorg Med Chem Lett · February 15, 2006 The design and synthesis of 4-hydroxytamoxifen (4-OHT) derivatives are described. The binding affinities of these compounds toward the orphan estrogen-related receptor gamma and the classical estrogen receptor alpha demonstrate that analogs bearing hydroxy ... Full text Link to item Cite

Coactivation of liver receptor homologue-1 by peroxisome proliferator-activated receptor gamma coactivator-1alpha on aromatase promoter II and its inhibition by activated retinoid X receptor suggest a novel target for breast-specific antiestrogen therapy.

Journal Article Cancer Res · December 15, 2005 Aromatase inhibitors target the production of estrogen in breast adipose tissue, but in doing so, also decrease estrogen formation in bone and other sites, giving rise to deleterious side effects, such as bone loss and arthralgia. Thus, it would be clinica ... Full text Link to item Cite

HDAC6 regulates Hsp90 acetylation and chaperone-dependent activation of glucocorticoid receptor.

Journal Article Mol Cell · May 27, 2005 The molecular chaperone heat shock protein 90 (Hsp90) and its accessory cochaperones function by facilitating the structural maturation and complex assembly of client proteins, including steroid hormone receptors and selected kinases. By promoting the acti ... Full text Link to item Cite

Identification and structure-activity relationship of phenolic acyl hydrazones as selective agonists for the estrogen-related orphan nuclear receptors ERRbeta and ERRgamma.

Journal Article J Med Chem · May 5, 2005 The first small molecule agonists of the estrogen-related receptors have been identified. GSK4716 (3) and GSK9089 (4) show binding to ERRgamma with remarkable selectivity over the classical estrogen receptors. Notably, in cell-based reporter assays, 3 mimi ... Full text Link to item Cite