Andrew Nixon

Overview:

Andrew Nixon, PhD, MBA (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

M.B.A. 2007

Duke University

Grants:

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

Printed Electronic Biosensors for Point-of-Care Testing of Cardiovascular Biomarkers

Administered By
Electrical and Computer Engineering
Awarded By
National Institutes of Health
Role
Co Investigator
Start Date
End Date

Publications:

Clinical development and evaluation of a VEGF-D assay in plasma from patients with metastatic colorectal cancer in the RAISE study.

<h4>Background</h4>Vascular endothelial growth factor (VEGF)-D was identified as a potential predictive biomarker for ramucirumab efficacy in second-line metastatic colorectal cancer using a research use only (RUO) assay. We describe results with a new assay for detecting VEGF-D in human plasma.<h4>Methods</h4>In RAISE (Clinical Trial Registration: NCT01183780), 1072 patients were randomized 1:1 to ramucirumab or placebo plus FOLFIRI. All patients were then randomized 1:2 to marker exploratory (ME) and marker confirmatory (MC) groups, and those with plasma samples were analyzed accordingly. A new assay validated for investigational use only (IUO) was used to measure VEGF-D levels in plasma, which were analyzed for correlation with overall and progression-free survival (OS/PFS). IUO assay data were compared with historical RUO assay data.<h4>Results</h4>ME subset analyses determined the optimal cutpoint of 5.4 ng/mL for defining high/low VEGF-D subgroups. In the combined ME/MC placebo arms, OS/PFS were numerically greater for patients with low vs high VEGF-D (OS: 12.8 vs 11.1 months; PFS: 5.6 vs 4.2 months). In patients with high VEGF-D, ramucirumab vs placebo demonstrated a numerically greater improvement in OS and PFS. Differential efficacy by VEGF-D level was statistically significant for PFS, but not OS.<h4>Conclusion</h4>In patients with high VEGF-D, ramucirumab demonstrated a greater improvement in OS and PFS vs placebo; however, baseline VEGF-D level was not predictive of ramucirumab OS benefit using VEGF-D assay for IUO. The RAISE intent-to-treat results remain valid.
Authors
Taniguchi, H; Yoshino, T; Yamaguchi, K; Yamazaki, K; Nixon, AB; Tabernero, J; Van Cutsem, E; Robling, KR; Abada, PB; Hozak, RR; Siegel, R; Fill, JA; Wijayawardana, S; Walgren, RA; Giles, B; Jones, A; Pitts, KR; Drove, N; Muro, K
MLA Citation
Taniguchi, Hiroya, et al. “Clinical development and evaluation of a VEGF-D assay in plasma from patients with metastatic colorectal cancer in the RAISE study.Current Medical Research and Opinion, vol. 37, no. 10, Oct. 2021, pp. 1769–78. Epmc, doi:10.1080/03007995.2021.1940908.
URI
https://scholars.duke.edu/individual/pub1487958
PMID
34229554
Source
epmc
Published In
Current Medical Research and Opinion
Volume
37
Published Date
Start Page
1769
End Page
1778
DOI
10.1080/03007995.2021.1940908

Pilot investigation of circulating angiogenic and inflammatory biomarkers associated with vascular malformations.

BACKGROUND: Vascular malformations in the central nervous system are difficult to monitor and treat due to their inaccessible location. Angiogenic and inflammatory proteins are secreted into the bloodstream and may serve as useful biomarkers for identifying patients at risk for complications or with certain disease phenotypes. METHODS: A validated multiplex protein array consisting of 26 angiogenic and inflammatory biomarkers (Angiome) was assessed in plasma isolated from healthy controls and patients with either sporadic brain arteriovenous malformation (BAVM), familial cerebral cavernous malformation (CCM), or hereditary hemorrhagic telangiectasia (HHT). These samples were obtained from archives of ongoing research studies at the University of California San Francisco and through prospective collection at the Toronto HHT Centre at St. Michael's Hospital. RESULTS: We compared circulating biomarker levels from each patient group to healthy controls and analyzed each pairwise combination of patient groups for differences in biomarker levels. Additionally, we analyzed the HHT samples to determine the association between biomarker levels and the following HHT-specific phenotypes, BAVM, pulmonary arteriovenous malformation (PAVM), liver vascular malformation (LVM), and gastrointestinal (GI) bleeding. Compared to controls, levels of SDF1 were significantly elevated in HHT patients (Proportional Increase [PI] = 1.87, p < 0.001, q = 0.011). Levels of sENG were significantly reduced in HHT patients compared to controls (PI = 0.56, p < 0.001, q < 0.001), reflecting the prevalence of HHT1 patients in this cohort. Levels of IL6 (PI = 3.22, p < 0.001, q < 0.001) and sTGFβR3 (PI = 0.70, p = 0.001, q < 0.029) differed significantly in CCM patients compared to controls. Compared to controls, ten of the biomarkers were significantly different in sporadic BAVM patients (q-values < 0.05). Among the pairwise combinations of patient groups, a significant elevation was observed in TGFβ1 in CCM patients compared to sporadic BAVM patients (PI = 2.30, p < 0.001, q = 0.034). When examining the association of circulating biomarker levels with HHT-specific phenotypes, four markers were significantly lower in HHT patients with BAVM (q-values < 0.05), and four markers were significantly higher in patients with LVM (q-values < 0.05). CONCLUSIONS: This pilot study suggests that the profile of circulating angiogenic and inflammatory biomarkers may be unique to each type of vascular malformation. Furthermore, this study indicates that circulating biomarkers may be useful for assessing phenotypic traits of vascular malformations.
Authors
Wetzel-Strong, SE; Weinsheimer, S; Nelson, J; Pawlikowska, L; Clark, D; Starr, MD; Liu, Y; Kim, H; Faughnan, ME; Nixon, AB; Marchuk, DA
MLA Citation
Wetzel-Strong, Sarah E., et al. “Pilot investigation of circulating angiogenic and inflammatory biomarkers associated with vascular malformations.Orphanet J Rare Dis, vol. 16, no. 1, Sept. 2021, p. 372. Pubmed, doi:10.1186/s13023-021-02009-7.
URI
https://scholars.duke.edu/individual/pub1496022
PMID
34479577
Source
pubmed
Published In
Orphanet Journal of Rare Diseases
Volume
16
Published Date
Start Page
372
DOI
10.1186/s13023-021-02009-7

Correction: Angiokines Associated with Outcomes after Sunitinib or Everolimus Treatment in Patients with Non-Clear Cell Renal Cell Carcinoma.

Authors
Armstrong, AJ; Nixon, AB; Carmack, A; Yang, Q; Eisen, T; Stadler, WM; Jones, RJ; Garcia, JA; Vaishampayan, UN; Picus, J; Hawkins, RE; Hainsworth, JD; Kollmannsberger, CK; Logan, TF; Puzanov, I; Pickering, LM; Ryan, CW; Protheroe, A; George, DJ; Halabi, S
MLA Citation
Armstrong, Andrew J., et al. “Correction: Angiokines Associated with Outcomes after Sunitinib or Everolimus Treatment in Patients with Non-Clear Cell Renal Cell Carcinoma.Clin Cancer Res, vol. 27, no. 12, June 2021, p. 3503. Pubmed, doi:10.1158/1078-0432.CCR-21-1636.
URI
https://scholars.duke.edu/individual/pub1486354
PMID
34117029
Source
pubmed
Published In
Clinical Cancer Research
Volume
27
Published Date
Start Page
3503
DOI
10.1158/1078-0432.CCR-21-1636

Pleural effusions associated with squamous cell lung carcinoma have a low diagnostic yield and a poor prognosis.

Background: Malignant pleural effusion (MPE) portends a poor prognosis in non-small cell lung cancer (NSCLC). However, the yield of pleural fluid cytology as well as survival of patients with MPE associated with squamous cell carcinoma versus adenocarcinoma is not well understood. We conducted this study to assess the diagnostic yield of pleural cytology and survival of patients with NSCLC related MPE. Methods: We performed a single-center, retrospective analysis of patients with NSCLC related MPE between 2010 and 2017. Kaplan-Meier method was used to compare survival and Cox proportional hazards analysis to assess if squamous cell cytopathology was associated with mortality. Results: We identified 277 patients, 29 with squamous cell and 248 with adenocarcinoma MPE. Pleural fluid cytology from initial thoracentesis was diagnostic in 13.8% (4/29) patients with squamous cell and 80.2% (199/248) with adenocarcinoma (P<0.001). Cytology from second thoracentesis was diagnostic in 13.3% (2/15) patients with squamous cell carcinoma, compared to 37.5% (12/32) with adenocarcinoma (P=0.17). There was no statistically significant difference in the pleural biopsy yield from medical pleuroscopy or video-assisted thoracoscopic surgery (VATS) in the two groups. The median survival of patients with squamous cell MPE was 112 [interquartile range (IQR): 44-220] days versus 194 (IQR: 54-523) days in adenocarcinoma (Log-rank test P=0.04). Multivariate Cox proportional hazards analysis showed that squamous cell cytopathology was independent predictor of mortality (hazard ratio for death of 1.73, 95% CI: 1.1-2.6; P=0.01). Conclusions: Pleural fluid cytology has a low diagnostic yield in squamous cell carcinoma MPE, and these patients have a poor survival compared to lung adenocarcinoma.
Authors
Dorry, M; Davidson, K; Dash, R; Jug, R; Clarke, JM; Nixon, AB; Mahmood, K
MLA Citation
Dorry, Michael, et al. “Pleural effusions associated with squamous cell lung carcinoma have a low diagnostic yield and a poor prognosis.Transl Lung Cancer Res, vol. 10, no. 6, June 2021, pp. 2500–08. Pubmed, doi:10.21037/tlcr-21-123.
URI
https://scholars.duke.edu/individual/pub1487860
PMID
34295657
Source
pubmed
Published In
Translational Lung Cancer Research
Volume
10
Published Date
Start Page
2500
End Page
2508
DOI
10.21037/tlcr-21-123

Plasma levels of angiopoietin-2, VEGF-A, and VCAM-1 as markers of bevacizumab-induced hypertension: CALGB 80303 and 90401 (Alliance).

Hypertension is a common toxicity induced by bevacizumab and other antiangiogenic drugs. There are no biomarkers to predict the risk of bevacizumab-induced hypertension. This study aimed to identify plasma proteins related to the function of the vasculature to predict the risk of severe bevacizumab-induced hypertension. Using pretreated plasma samples from 398 bevacizumab-treated patients in two clinical trials (CALGB 80303 and 90401), the levels of 17 proteins were measured via ELISA. The association between proteins and grade 3 bevacizumab-induced hypertension was performed by calculating the odds ratio (OR) from logistic regression adjusting for age, sex, and clinical trial. Using the optimal cut-point of each protein, sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) for hypertension were estimated. Five proteins showed no difference in levels between clinical trials and were used for analyses. Lower levels of angiopoietin-2 (p = 0.0013, OR 3.41, 95% CI 1.67-7.55), VEGF-A (p = 0.0008, OR 4.25, 95% CI 1.93-10.72), and VCAM-1 (p = 0.0067, OR 2.68, 95% CI 1.34-5.63) were associated with an increased risk of grade 3 hypertension. The multivariable model suggests independent effects of angiopoietin-2 (p = 0.0111, OR 2.71, 95% CI 1.29-6.10), VEGF-A (p = 0.0051, OR 3.66, 95% CI 1.54-9.73), and VCAM-1 (p = 0.0308, OR 2.27, 95% CI 1.10-4.92). The presence of low levels of 2-3 proteins had an OR of 10.06 (95% CI 3.92-34.18, p = 1.80 × 10-5) for the risk of hypertension, with sensitivity of 89.7%, specificity of 53.5%, PPV of 17.3%, and NPV of 97.9%. This is the first study providing evidence of plasma proteins with potential value to predict patients at risk of developing bevacizumab-induced hypertension.Clinical trial registration: ClinicalTrials.gov Identifier: NCT00088894 (CALGB 80303); and NCT00110214 (CALGB 90401).
Authors
Quintanilha, JCF; Liu, Y; Etheridge, AS; Yazdani, A; Kindler, HL; Kelly, WK; Nixon, AB; Innocenti, F
MLA Citation
Quintanilha, Julia C. F., et al. “Plasma levels of angiopoietin-2, VEGF-A, and VCAM-1 as markers of bevacizumab-induced hypertension: CALGB 80303 and 90401 (Alliance).Angiogenesis, May 2021. Pubmed, doi:10.1007/s10456-021-09799-1.
URI
https://scholars.duke.edu/individual/pub1483223
PMID
34028627
Source
pubmed
Published In
Angiogenesis
Published Date
DOI
10.1007/s10456-021-09799-1