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Dive into the research topics where Emily O'Day is active.

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Featured researches published by Emily O'Day.


Cancer Discovery | 2018

Genomic Heterogeneity as a Barrier to Precision Medicine in Gastroesophageal Adenocarcinoma

Eirini Pectasides; Matthew D. Stachler; Sarah Derks; Yang Liu; Steven Brad Maron; Mirazul Islam; Lindsay Alpert; Heewon A. Kwak; Hedy L. Kindler; Blase N. Polite; Manish R. Sharma; Kenisha Allen; Emily O'Day; S Lomnicki; Melissa Maranto; Rajani Kanteti; Carrie Fitzpatrick; Christopher R. Weber; Namrata Setia; Shu-Yuan Xiao; John Hart; Rebecca J. Nagy; Kyoung-Mee Kim; Min-Gew Choi; Byung-Hoon Min; Katie S. Nason; Lea O'Keefe; Masayuki Watanabe; Hideo Baba; Rick Lanman

Gastroesophageal adenocarcinoma (GEA) is a lethal disease where targeted therapies, even when guided by genomic biomarkers, have had limited efficacy. A potential reason for the failure of such therapies is that genomic profiling results could commonly differ between the primary and metastatic tumors. To evaluate genomic heterogeneity, we sequenced paired primary GEA and synchronous metastatic lesions across multiple cohorts, finding extensive differences in genomic alterations, including discrepancies in potentially clinically relevant alterations. Multiregion sequencing showed significant discrepancy within the primary tumor (PT) and between the PT and disseminated disease, with oncogene amplification profiles commonly discordant. In addition, a pilot analysis of cell-free DNA (cfDNA) sequencing demonstrated the feasibility of detecting genomic amplifications not detected in PT sampling. Lastly, we profiled paired primary tumors, metastatic tumors, and cfDNA from patients enrolled in the personalized antibodies for GEA (PANGEA) trial of targeted therapies in GEA and found that genomic biomarkers were recurrently discrepant between the PT and untreated metastases. Divergent primary and metastatic tissue profiling led to treatment reassignment in 32% (9/28) of patients. In discordant primary and metastatic lesions, we found 87.5% concordance for targetable alterations in metastatic tissue and cfDNA, suggesting the potential for cfDNA profiling to enhance selection of therapy.Significance: We demonstrate frequent baseline heterogeneity in targetable genomic alterations in GEA, indicating that current tissue sampling practices for biomarker testing do not effectively guide precision medicine in this disease and that routine profiling of metastatic lesions and/or cfDNA should be systematically evaluated. Cancer Discov; 8(1); 37-48. ©2017 AACR.See related commentary by Sundar and Tan, p. 14See related article by Janjigian et al., p. 49This article is highlighted in the In This Issue feature, p. 1.


Cancer | 2017

MET tyrosine kinase receptor expression and amplification as prognostic biomarkers of survival in gastroesophageal adenocarcinoma.

Daniel V.T. Catenacci; Agnes Ang; Wei-Li Liao; Jing Shen; Emily O'Day; Robert Loberg; Fabiola Cecchi; Todd Hembrough; Annamaria Ruzzo; Francesco Graziano

MET gene amplification and Met protein overexpression may be associated with a poor prognosis. The MET/Met status is typically determined with fluorescence in situ hybridization (FISH) and immunohistochemistry (IHC), respectively. Targeted proteomics uses mass spectrometry–based selected reaction monitoring (SRM) to accurately quantitate Met expression. FISH, IHC, and SRM analyses were compared to characterize the prognostic value of MET/Met in gastroesophageal adenocarcinoma (GEC).


Cancer Discovery | 2018

Targeted Therapies for Targeted Populations: Anti-EGFR Treatment for EGFR-Amplified Gastroesophageal Adenocarcinoma

Steven Brad Maron; Lindsay Alpert; Heewon A. Kwak; S Lomnicki; Leah Chase; David Xu; Emily O'Day; Rebecca J. Nagy; Richard B. Lanman; Fabiola Cecchi; Todd Hembrough; Alexa B. Schrock; John Hart; Shu-Yuan Xiao; Namrata Setia; Daniel V.T. Catenacci

Previous anti-EGFR trials in unselected patients with gastroesophageal adenocarcinoma (GEA) were resoundingly negative. We identified EGFR amplification in 5% (19/363) of patients at the University of Chicago, including 6% (8/140) who were prospectively screened with intention-to-treat using anti-EGFR therapy. Seven patients received ≥1 dose of treatment: three first-line FOLFOX plus ABT-806, one second-line FOLFIRI plus cetuximab, and three third/fourth-line cetuximab alone. Treatment achieved objective response in 58% (4/7) and disease control in 100% (7/7) with a median progression-free survival of 10 months. Pretreatment and posttreatment tumor next-generation sequencing (NGS), serial plasma circulating tumor DNA (ctDNA) NGS, and tumor IHC/FISH for EGFR revealed preexisting and/or acquired genomic events, including EGFR-negative clones, PTEN deletion, KRAS amplification/mutation, NRAS, MYC, and HER2 amplification, and GNAS mutations serving as mechanisms of resistance. Two evaluable patients demonstrated interval increase of CD3+ infiltrate, including one who demonstrated increased NKp46+, and PD-L1 IHC expression from baseline, suggesting an immune therapeutic mechanism of action. EGFR amplification predicted benefit from anti-EGFR therapy, albeit until various resistance mechanisms emerged.Significance: This paper highlights the role of EGFR inhibitors in EGFR-amplified GEA-despite negative results in prior unselected phase III trials. Using serial ctDNA and tissue NGS, we identified mechanisms of primary and acquired resistance in all patients, as well as potential contribution of antibody-dependent cell-mediated cytotoxicity to their clinical benefit. Cancer Discov; 8(6); 696-713. ©2018 AACR.See related commentary by Strickler, p. 679This article is highlighted in the In This Issue feature, p. 663.


Journal of Clinical Oncology | 2015

Her2 expression in gastroesophageal cancer (GEC) FFPE tissue using mass spectrometry (MS) and correlation with HER2 gene amplification.

Daniel Virgil Thomas Catenacci; Lei Zhao; Emma Whitcomb; Les Henderson; Emily O'Day; Peng Xu; Shu-Yuan Xiao; Sang Mee Lee; Wei-Li Liao; Sheeno Thyparambil; Jamar Uzzell; Marlene Darfler; David B. Krizman; Jon Burrows; Todd Hembrough

82 Background: HER2+ GEC derived benefit from trastuzumab. Her2 IHC is semi-quantitative, subjective, and sensitive to antigen instability; HER2 FISH is laborious, expensive, and subjective. False positivity/negativity have been described. Also, these are low throughput assays; there is known molecular heterogeneity, with several putative biomarkers, and only scarce tissue to assess for each. We sought to evaluate the association of Her2 MS expression with HER2 FISH, along with other markers within the ‘GEC-plex’. Methods: We utilized a previously described unique Her2 peptide and quantification method (Hembrough et al J Clin Oncol 32,2014(suppl 3;abstr17)). The assay was run on 27 cell lines, in parallel with HER2:CEP17 FISH. Her2 expression thresholds were established for HER2 amplification using ROC curves. We adjusted for Her3, Egfr, and Met MS expression levels and sample HER2:CEP17 ratio heterogeneity in a multiple linear regression model. The model/cut-offs were then validated prospectively on GEC ...


Gastric Cancer | 2016

Mass-spectrometry-based quantitation of Her2 in gastroesophageal tumor tissue: comparison to IHC and FISH

Daniel V.T. Catenacci; Wei-Li Liao; Lei Zhao; Emma Whitcomb; Les Henderson; Emily O'Day; Peng Xu; Sheeno Thyparambil; David B. Krizman; Kathleen Bengali; Jamar Uzzell; Marlene Darfler; Fabiola Cecchi; A. Blackler; Yung-Jue Bang; John Hart; Shu-Yuan Xiao; Lee Sm; Jon Burrows; Todd Hembrough


Journal of The National Comprehensive Cancer Network | 2016

Therapeutically Induced Changes in HER2, HER3, and EGFR Protein Expression for Treatment Guidance

Shankar Sellappan; Adele Blackler; Wei-Li Liao; Emily O'Day; Peng Xu; Sheeno Thyparambil; Fabiola Cecchi; Todd Hembrough; Daniel V.T. Catenacci


Journal of Clinical Oncology | 2015

MET as a prognostic biomarker of survival in a large cohort of patients with gastroesophageal cancer (GEC).

Daniel Virgil Thomas Catenacci; Rui Tang; Kelly S. Oliner; Agnes Ang; Robert D. Loberg; Emily O'Day; Peng Xu; Les Henderson; Annamaria Ruzzo; Francesco Graziano


Journal of Clinical Oncology | 2017

Molecular profiling of advanced pancreatic cancer (PC) patients from a phase I/II study using circulating tumor DNA.

Daniel V.T. Catenacci; Emma Green; Michael Epstein; Greg Jones; Clive D. Morris; Emily O'Day; S Lomnicki; Melissa Maranto; Theodore Karrison; Hedy L. Kindler


Journal of Clinical Oncology | 2017

Anti-EGFR treatment for EGFR-amplified gastroesophageal adenocarcinoma.

Steven Brad Maron; Lindsay Alpert; David Xu; Rachel Rendak; Emily O'Day; Namrata Setia; Daniel V.T. Catenacci


Journal of Clinical Oncology | 2016

KRAS gene amplification to define a distinct molecular subgroup of gastroesophageal adenocarcinoma.

Les Henderson; Peng Xu; Emily O'Day; Fabiola Cecchi; Adele Blackler; Wei-Li Liao; Todd Hembrough; Daniel V.T. Catenacci

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Peng Xu

University of Chicago

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John Hart

University of Chicago

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