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Mettu, Niharika Bansal

Overview:

My long-term goal is to develop new therapies to treat patients with gastrointestinal and other solid tumors. To accomplish this, I am active in designing, writing, and running phase I and II clinical trials. I am also interested in the correlative science that furthers our understanding of cancer at a molecular level. I am interested in the identification of biomarkers, which are characteristics of a given patient's tumor that may help us to understand his or her prognosis or how well he or she may respond to a given therapy. The overall objective of this research is to use the knowledge gained to personalize care and find the very best therapies that will enable our patients to fight their cancer.

Positions:

Assistant Professor of Medicine

Medicine, Medical Oncology
School of Medicine

Member of the Duke Cancer Institute

Duke Cancer Institute
School of Medicine

Education:

Ph.D. 2007

Ph.D. — Duke University

M.D. 2008

M.D. — Duke University School of Medicine

Internal Medicine Residency, Medicine

Duke University School of Medicine

Hematology-Oncology Fellowship, Medicine

Duke University School of Medicine

Grants:

MedImmune Panc D607C00005

Administered By
Duke Cancer Institute
AwardedBy
AstraZeneca LP
Role
Principal Investigator
Start Date
November 13, 2018
End Date
October 28, 2023

A Phase 1/2 study of exploring the safety tolerablility and efficacy of Epacadostat in combination with Durvalumab in subjects with selected advanced solid tumors.

Administered By
Duke Cancer Institute
AwardedBy
Incyte Corporation
Role
Principal Investigator
Start Date
October 01, 2016
End Date
September 30, 2021

A Phase I open label dose escalation safety and tolerability study of INCB054828 in subjects with advanced malignancies

Administered By
Duke Cancer Institute
AwardedBy
Incyte Corporation
Role
Principal Investigator
Start Date
September 01, 2015
End Date
August 31, 2020

AM0010-301 A Randomized Phase 3 Study of AM0010 in Combination with FOLFOX Compared

Administered By
Duke Cancer Institute
AwardedBy
ARMO BioSciences
Role
Principal Investigator
Start Date
June 15, 2017
End Date
June 20, 2020

BACCI - RU021416 Phase II Study

Administered By
Duke Cancer Institute
AwardedBy
Academic and Community Cancer Research United
Role
Principal Investigator
Start Date
June 16, 2017
End Date
May 31, 2020

OncoMed OMP-313M32

Administered By
Duke Cancer Institute
AwardedBy
OncoMed Pharmaceuticals
Role
Principal Investigator
Start Date
October 23, 2017
End Date
September 30, 2019

A Phase 1/2 study of the safety, tolorability and efficacy of INCB24360 administered in combination with Nivolumab in select advanced cancers.

Administered By
Duke Cancer Institute
AwardedBy
Incyte Corporation
Role
Principal Investigator
Start Date
April 01, 2015
End Date
March 30, 2019

ATELIER ML39832 PI Initiated

Administered By
Duke Cancer Institute
AwardedBy
Genetech
Role
Principal Investigator
Start Date
June 28, 2018
End Date
July 27, 2018

A Phase 2 proof of concept study of ACP-196 alone in combination with Pembrolizumab in subjects with advanced or metastatic pancreatic cancer.

Administered By
Duke Cancer Institute
AwardedBy
Acerta Pharma
Role
Principal Investigator
Start Date
May 01, 2015
End Date
May 24, 2018

A Multi center study of the Bruton's Tyrosine Kinase (BTK) inhibitor, Ibrutinib in combination with MEDI4736

Administered By
Duke Cancer Institute
AwardedBy
Pharmacyclics, Inc.
Role
Principal Investigator
Start Date
October 01, 2015
End Date
February 22, 2018

Preclinical and Human Correlative Studies of a Novel Bruton Tyronsine Kinase Inhibitor in Pancreatic Cancer

Administered By
Medicine, Medical Oncology
AwardedBy
Department of Defense
Role
Principal Investigator
Start Date
September 30, 2016
End Date
September 29, 2017
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Publications:

Clinical Insights Into the Biology and Treatment of Pancreatic Cancer.

Pancreatic cancer is a devastating disease with a universally poor prognosis. In 2015, it is estimated that there will be 48,960 new cases of pancreatic cancer and that 40,560 people will die of the disease. The 5-year survival rate is 7.2% for all patients with pancreatic cancer; however, survival depends greatly on the stage at diagnosis. Unfortunately, 53% of patients already have metastatic disease at diagnosis, which corresponds to a 5-year survival rate of 2.4%. Even for the 9% of patients with localized disease confined to the pancreas, the 5-year survival is still modest at only 27.1%. These grim statistics highlight the need for ways to identify cohorts of individuals at highest risk, methods to screen those at highest risk to identify preinvasive pathologic precursors, and development of effective systemic therapies. Recent clinical and translational progress has emphasized the relationship with diabetes, the role of the stroma, and the interplay of each of these with inflammation in the pathobiology of pancreatic cancer. In this article, we will discuss these relationships and how they might translate into novel management strategies for the treatment of this disease.

Authors
Mettu, NB; Abbruzzese, JL
MLA Citation
Mettu, NB, and Abbruzzese, JL. "Clinical Insights Into the Biology and Treatment of Pancreatic Cancer." Journal of Oncology Practice 12.1 (January 2016): 17-23. (Review)
Website
http://hdl.handle.net/10161/11572
PMID
26759461
Source
epmc
Published In
Journal of Oncology Practice
Volume
12
Issue
1
Publish Date
2016
Start Page
17
End Page
23
DOI
10.1200/jop.2015.009092

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, NB, Hurwitz, H, and Hsu, DS. "Use of molecular biomarkers to inform adjuvant therapy for colon cancer." ONCOLOGY (United States) 27.8 (August 14, 2013). (Review)
Source
scopus
Published In
Oncology (Williston Park, N.Y.)
Volume
27
Issue
8
Publish Date
2013

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, NB, Hurwitz, H, and Hsu, DS. "Use of molecular biomarkers to inform adjuvant therapy for colon cancer." Oncology (Williston Park, N.Y.) 27.8 (August 2013): 746-754. (Review)
PMID
24133820
Source
epmc
Published In
Oncology (Williston Park, N.Y.)
Volume
27
Issue
8
Publish Date
2013
Start Page
746
End Page
754

Muehrcke's lines as a diagnostic clue to increased catabolism and a severe systemic disease state.

Authors
Stanifer, J; Mehta, R; Mettu, N; Sanders, J; Setji, N
MLA Citation
Stanifer, J, Mehta, R, Mettu, N, Sanders, J, and Setji, N. "Muehrcke's lines as a diagnostic clue to increased catabolism and a severe systemic disease state." The American Journal of the Medical Sciences 342.4 (October 2011): 331-null.
PMID
21760477
Source
epmc
Published In
The American Journal of the Medical Sciences
Volume
342
Issue
4
Publish Date
2011
Start Page
331
DOI
10.1097/maj.0b013e31821fb6d0

The nuclear receptor-coactivator interaction surface as a target for peptide antagonists of the peroxisome proliferator-activated receptors.

The peroxisome proliferator-activated receptors (PPARalpha, PPARdelta, and PPARgamma) constitute a family of nuclear receptors that regulates metabolic processes involved in lipid and glucose homeostasis. Although generally considered to function as ligand-regulated receptors, all three PPARs exhibit a high level of constitutive activity that may result from their stimulation by intracellularly produced endogenous ligands. Consequently, complete inhibition of PPAR signaling requires the development of inverse agonists. However, the currently available small molecule antagonists for the PPARs function only as partial agonists, or their efficacy is not sufficient to inhibit the constitutive activity of these receptors. Due to the lack of efficacious antagonists that interact with the ligand-binding domain of the PPARs, we decided to target an interaction that is central to nuclear receptor-mediated gene transcription: the nuclear receptor-coactivator interaction. We utilized phage display technology to identify short LXXLL-containing peptides that bind to the PPARs. Analysis of these peptides revealed a consensus binding motif consisting of HPLLXXLL. Cross-screening of these peptides for binding to other nuclear receptors enabled the identification of a high-affinity PPAR-selective peptide that has the ability to repress PPARgamma1-dependent transcription of transfected reporter genes. Most importantly, when introduced into HepG2 cells, the peptide inhibited the expression of endogenous PPARgamma1 target genes, adipose differentiation-related protein and mitochondrial 3-hydroxy-3-methylglutaryl coenzyme A synthase 2. This work lends support for the rational development of peptidomimetics that block receptor-mediated transcription by targeting the nuclear receptor-coactivator interaction surface.

Authors
Mettu, NB; Stanley, TB; Dwyer, MA; Jansen, MS; Allen, JE; Hall, JM; McDonnell, DP
MLA Citation
Mettu, NB, Stanley, TB, Dwyer, MA, Jansen, MS, Allen, JE, Hall, JM, and McDonnell, DP. "The nuclear receptor-coactivator interaction surface as a target for peptide antagonists of the peroxisome proliferator-activated receptors." Mol Endocrinol 21.10 (October 2007): 2361-2377.
PMID
17595321
Source
pubmed
Published In
Molecular Endocrinology (Baltimore, Md.)
Volume
21
Issue
10
Publish Date
2007
Start Page
2361
End Page
2377
DOI
10.1210/me.2007-0201
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