Andrew Nixon

Overview:

Andrew Nixon, PhD, MBA (Associate Professor of Medicine) is Director of the Phase I Biomarker Laboratory, which brings together clinical, translational and basic research to pursue the development of novel biomarkers defining mechanisms of sensitivity, resistance, and toxicity to given therapeutic drug classes, particularly anti-angiogenic agents. Additionally, the laboratory has been appointed as a Molecular Reference Laboratory for the Alliance oncology cooperative group, a national clinical trial research group sponsored by the National Cancer Institute. The laboratory has quality control procedures in place to address many of the issues involved in clinical trial research including determination of sample quantity, sample integrity, and sample heterogeneity. We have spent considerable time developing robust assays that utilize limited amounts of specimen while providing high quality data. Multiplex ELISA and gene expression arrays are used to analyze serially collected blood and paraffin samples archived from cancer patient clinical trials. This work has the potential to improve the efficacy and toxicity of current therapies and to guide the development of the next generation of anti-angiogenesis therapies for cancer and other diseases.

Positions:

Professor in Medicine

Medicine, Medical Oncology
School of Medicine

Member of the Duke Cancer Institute

Duke Cancer Institute
School of Medicine

Education:

Ph.D. 1997

Wake Forest University

Grants:

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

Administered By
Medicine, Medical Oncology
Awarded By
Department of Defense
Role
Co Investigator
Start Date
End Date

Plasma Angiome and Serum Androgens as Predictors of Overall Survival in Metastatic Prostate Cancer

Administered By
Biostatistics & Bioinformatics
Awarded By
Department of Defense
Role
Partnering PI
Start Date
End Date

(PQA5) 'Dose and Mechanisms of Exercise in Breast Cancer Prevention'

Administered By
Radiation Oncology
Awarded By
National Institutes of Health
Role
Co Investigator
Start Date
End Date

Anti-VEGF in Tumors & Wounds: Efficacy vs Toxicity

Administered By
Medicine, Medical Oncology
Awarded By
National Institutes of Health
Role
Co Investigator
Start Date
End Date

Regulation Of Cyclic Gmp Phosphodiesterase By Gz

Administered By
Pharmacology & Cancer Biology
Awarded By
National Institutes of Health
Role
PI-Fellow
Start Date
End Date

Publications:

A phase II study of savolitinib (volitinib, AZD6094, HMPL-504) in subjects with MET amplified metastatic colorectal cancer (mCRC) detected by cell-free (cf)DNA

Authors
Jia, J; Niedzwiecki, D; Arrowood, C; Garett-Mead, N; Nagy, R; Lanman, RB; Wright, J; Nixon, AB; Strickler, JH
URI
https://scholars.duke.edu/individual/pub1444228
Source
wos-lite
Published In
Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology
Volume
38
Published Date

Prognostic and Predictive Biomarkers in Metastatic Colorectal Cancer Patients Receiving Regorafenib.

Regorafenib is a tyrosine kinase inhibitor approved by the Food and Drug Administration (FDA) for the treatment of chemotherapy-refractory metastatic colorectal cancer (mCRC) patients. Regorafenib inhibits signaling through multiple receptors associated with angiogenesis, metastasis, and tumor immunity. Here we report biomarker results from LCCC1029, a randomized, placebo controlled, phase II trial of chemotherapy ± regorafenib in second-line mCRC patients. A panel of 20 soluble protein biomarkers (termed the Angiome) was assessed in the plasma of 149 patients from the LCCC1029 trial both at baseline and along the treatment continuum. Baseline protein levels were analyzed for prognostic and predictive value for progression-free survival (PFS) and overall survival (OS). Changes in protein levels during treatment were analyzed for potential pharmacodynamic effects. Six markers (HGF, IL-6, PlGF, VEGF-R1, OPN, and IL-6R) were found to be prognostic for PFS. Nine markers (IL-6, TIMP-1, PlGF, VCAM-1, ICAM-1, OPN, TSP-2, HGF, and VEGF-R1) were prognostic for OS. Higher baseline levels of OPN (Pintx=0.0167), VCAM-1 (Pintx=0.0216), and PDGF-AA (Pintx=0.0435) appeared to predict for PFS benefit from regorafenib compared to placebo. VCAM-1 was also potentially predictive of OS benefit from regorafenib compared to placebo (Pintx=0.0124). On-treatment changes of six markers reflected potential on-target effect of regorafenib. Consistent results were observed in an Italian cohort where 105 late-stage mCRC patients received regorafenib monotherapy. The key findings of this study suggest that VCAM-1 may be a predictive biomarker for regorafenib benefit while multiple protein markers may be prognostic of outcome in mCRC patients.
Authors
Liu, Y; Lyu, J; Bell Burdett, K; Sibley, AB; Hatch, AJ; Starr, MD; Brady, JC; Hammond, K; Marmorino, F; Rossini, D; Goldberg, RM; Falcone, A; Cremolini, C; Owzar, K; Ivanova, A; Moore, DT; Lee, MS; Sanoff, HK; Innocenti, F; Nixon, AB
MLA Citation
Liu, Yingmiao, et al. “Prognostic and Predictive Biomarkers in Metastatic Colorectal Cancer Patients Receiving Regorafenib.Mol Cancer Ther, Aug. 2020. Pubmed, doi:10.1158/1535-7163.MCT-20-0249.
URI
https://scholars.duke.edu/individual/pub1453716
PMID
32747417
Source
pubmed
Published In
Mol Cancer Ther
Published Date
DOI
10.1158/1535-7163.MCT-20-0249

A tumor-intrinsic PD-L1/NLRP3 inflammasome signaling pathway drives resistance to anti-PD-1 immunotherapy.

An in-depth understanding of immune escape mechanisms in cancer is likely to lead to innovative advances in immunotherapeutic strategies. However, much remains unknown regarding these mechanisms and how they impact immunotherapy resistance. Using several preclinical tumor models as well as clinical specimens, we identified a mechanism whereby CD8+ T cell activation in response to programmed cell death 1 (PD-1) blockade induced a programmed death ligand 1/NOD-, LRR-, and pyrin domain-containing protein 3 (PD-L1/NLRP3) inflammasome signaling cascade that ultimately led to the recruitment of granulocytic myeloid-derived suppressor cells (PMN-MDSCs) into tumor tissues, thereby dampening the resulting antitumor immune response. The genetic and pharmacologic inhibition of NLRP3 suppressed PMN-MDSC tumor infiltration and significantly augmented the efficacy of anti-PD-1 antibody immunotherapy. This pathway therefore represents a tumor-intrinsic mechanism of adaptive resistance to anti-PD-1 checkpoint inhibitor immunotherapy and is a promising target for future translational research.
Authors
Theivanthiran, B; Evans, KS; DeVito, NC; Plebanek, M; Sturdivant, M; Wachsmuth, LP; Salama, AK; Kang, Y; Hsu, D; Balko, JM; Johnson, DB; Starr, M; Nixon, AB; Holtzhausen, A; Hanks, BA
MLA Citation
Theivanthiran, Balamayoora, et al. “A tumor-intrinsic PD-L1/NLRP3 inflammasome signaling pathway drives resistance to anti-PD-1 immunotherapy.J Clin Invest, vol. 130, no. 5, May 2020, pp. 2570–86. Pubmed, doi:10.1172/JCI133055.
URI
https://scholars.duke.edu/individual/pub1431106
PMID
32017708
Source
pubmed
Published In
J Clin Invest
Volume
130
Published Date
Start Page
2570
End Page
2586
DOI
10.1172/JCI133055

The targeting of leukocytes by 5-oxo-eicosanoids

Authors
OFlaherty, JT; Kuroki, M; Daniel, LW; Wykle, RL; Nixon, AB; Sozzani, S
MLA Citation
OFlaherty, J. T., et al. “The targeting of leukocytes by 5-oxo-eicosanoids.” Frontiers in Bioactive Lipids, edited by J. Y. Vanderhoek, PLENUM PRESS DIV PLENUM PUBLISHING CORP, 1996, pp. 149–55.
URI
https://scholars.duke.edu/individual/pub1438791
Source
wos
Published In
Frontiers in Bioactive Lipids
Published Date
Start Page
149
End Page
155

Predictive Blood-Based Biomarkers in Patients with Epithelial Ovarian Cancer Treated with Carboplatin and Paclitaxel with or without Bevacizumab: Results from GOG-0218.

PURPOSE: GOG-0218, a double-blind placebo-controlled phase III trial, compared carboplatin and paclitaxel with placebo, bevacizumab followed by placebo, or bevacizumab followed by bevacizumab in advanced epithelial ovarian cancer (EOC). Results demonstrated significantly improved progression-free survival (PFS), but no overall survival (OS) benefit with bevacizumab. Blood samples were collected for biomarker analyses. EXPERIMENTAL DESIGN: Plasma samples were analyzed via multiplex ELISA technology for seven prespecified biomarkers [IL6, Ang-2, osteopontin (OPN), stromal cell-derived factor-1 (SDF-1), VEGF-D, IL6 receptor (IL6R), and GP130]. The predictive value of each biomarker with respect to PFS and OS was assessed using a protein marker by treatment interaction term within the framework of a Cox proportional hazards model. Prognostic markers were identified using Cox models adjusted for baseline covariates. RESULTS: Baseline samples were available from 751 patients. According to our prespecified analysis plan, IL6 was predictive of a therapeutic advantage with bevacizumab for PFS (P = 0.007) and OS (P = 0.003). IL6 and OPN were found to be negative prognostic markers for both PFS and OS (P < 0.001). Patients with high median IL6 levels (dichotomized at the median) treated with bevacizumab had longer PFS (14.2 vs. 8.7 months) and OS (39.6 vs. 33.1 months) compared with placebo. CONCLUSIONS: The inflammatory cytokine IL6 may be predictive of therapeutic benefit from bevacizumab when combined with carboplatin and paclitaxel. Aligning with results observed in patients with renal cancer treated with antiangiogenic therapies, it appears plasma IL6 may also define those patients with EOC more or less likely to benefit from the addition of bevacizumab to standard chemotherapy.
Authors
Alvarez Secord, A; Bell Burdett, K; Owzar, K; Tritchler, D; Sibley, AB; Liu, Y; Starr, MD; Brady, JC; Lankes, HA; Hurwitz, HI; Mannel, RS; Tewari, KS; O'Malley, DM; Gray, H; Bakkum-Gamez, JN; Fujiwara, K; Boente, M; Deng, W; Burger, RA; Birrer, MJ; Nixon, AB
MLA Citation
Alvarez Secord, Angeles, et al. “Predictive Blood-Based Biomarkers in Patients with Epithelial Ovarian Cancer Treated with Carboplatin and Paclitaxel with or without Bevacizumab: Results from GOG-0218.Clin Cancer Res, vol. 26, no. 6, Mar. 2020, pp. 1288–96. Pubmed, doi:10.1158/1078-0432.CCR-19-0226.
URI
https://scholars.duke.edu/individual/pub1427139
PMID
31919136
Source
pubmed
Published In
Clinical Cancer Research : an Official Journal of the American Association for Cancer Research
Volume
26
Published Date
Start Page
1288
End Page
1296
DOI
10.1158/1078-0432.CCR-19-0226