Neil Spector
Positions:
Sandra Coates Associate Professor
Medicine, Medical Oncology
School of Medicine
Associate Professor of Medicine
Medicine, Medical Oncology
School of Medicine
Associate Professor of Pharmacology & Cancer Biology
Pharmacology & Cancer Biology
School of Medicine
Member of the Duke Cancer Institute
Duke Cancer Institute
School of Medicine
Education:
M.D. 1982
University of Medicine and Dentistry of New Jersey
Intern, Medicine
University of Texas at Dallas
First Year Neurology Resident, Neurology
University of Texas at Dallas
Medical Resident, Medicine
University of Texas at Dallas
Grants:
Immunolight 2019 Renewal
Administered By
Biomedical Engineering
Role
Co-Principal Investigator
Start Date
End Date
Circumventing Therapeutic Resistance and the Emergency of Disseminated Breast Cancer Cells through Non-Invasive Optical
Administered By
Duke Cancer Institute
Role
Principal Investigator
Start Date
End Date
The Role of HER2 Signaling Networks in Early Stage Breast Cancer Initiation and Resistance to Tamoxifen Prevention
Administered By
Medicine, Medical Oncology
Role
Co Investigator
Start Date
End Date
ACOSOG Competing Renewal
Administered By
Duke Clinical Research Institute
Awarded By
National Institutes of Health
Role
Committee Chair
Start Date
End Date
Quantitative and Qualitative Differential Expression Proteomics
Administered By
Institutes and Centers
Awarded By
National Institutes of Health
Role
Major User
Start Date
End Date
Publications:
Perspectives on Inflammatory Breast Cancer (IBC) Research, Clinical Management and Community Engagement from the Duke IBC Consortium.
Inflammatory breast cancer (IBC) is an understudied and aggressive form of breast cancer with a poor prognosis, accounting for 2-6% of new breast cancer diagnoses but 10% of all breast cancer-related deaths in the United States. Currently there are no therapeutic regimens developed specifically for IBC, and it is critical to recognize that all aspects of treating IBC - including staging, diagnosis, and therapy - are vastly different than other breast cancers. In December 2014, under the umbrella of an interdisciplinary initiative supported by the Duke School of Medicine, researchers, clinicians, research administrators, and patient advocates formed the Duke Consortium for IBC to address the needs of patients in North Carolina (an ethnically and economically diverse state with 100 counties) and across the Southeastern United States. The primary goal of this group is to translate research into action and improve both awareness and patient care through collaborations with local, national and international IBC programs. The consortium held its inaugural meeting on Feb 28, 2018, which also marked Rare Disease Day and convened national research experts, clinicians, patients, advocates, government representatives, foundation leaders, staff, and trainees. The meeting focused on new developments and challenges in the clinical management of IBC, research challenges and opportunities, and an interactive session to garner input from patients, advocates, and community partners that would inform a strategic plan toward continuing improvements in IBC patient care, research, and education.
Authors
Devi, GR; Hough, H; Barrett, N; Cristofanilli, M; Overmoyer, B; Spector, N; Ueno, NT; Woodward, W; Kirkpatrick, J; Vincent, B; Williams, KP; Finley, C; Duff, B; Worthy, V; McCall, S; Hollister, BA; Palmer, G; Force, J; Westbrook, K; Fayanju, O; Suneja, G; Dent, SF; Hwang, ES; Patierno, SR; Marcom, PK
MLA Citation
Devi, Gayathri R., et al. “Perspectives on Inflammatory Breast Cancer (IBC) Research, Clinical Management and Community Engagement from the Duke IBC Consortium.” J Cancer, vol. 10, no. 15, 2019, pp. 3344–51. Pubmed, doi:10.7150/jca.31176.
URI
https://scholars.duke.edu/individual/pub1395729
PMID
31293637
Source
pubmed
Published In
Journal of Cancer
Volume
10
Published Date
Start Page
3344
End Page
3351
DOI
10.7150/jca.31176
CHAMBER: A Regional Performance Improvement CME Initiative for Breast Cancer Health Care Providers.
CHAMBER was a regional educational initiative for providers of care to patients with HER2+ breast cancer. The study goals were to (1) enhance testing for HER2/neu overexpression in patients with invasive breast cancer; (2) increase the appropriate use of targeted therapy for patients with HER2+ breast cancer; and (3) enhance patients' coping ability. This Performance Improvement Continuing Medical Education (PI-CME) initiative included clinical practice assessment, educational activities, and reassessment. Chart review revealed a high rate of HER2 testing (98%) before and after education. Targeted therapy for patients with HER2+ breast cancer declined after the program (from 96% to 61%), perhaps attributable to an increase in awareness of medical reasons to avoid use of targeted therapy. Assessment for patients' emotional coping ability increased after education (from 55% to 76%; P=.01). Rates of testing for HER2 amplification and assessment of emotional well-being after education were consistent with ASCO Quality Oncology Practice Initiative benchmark values. Documentation of actions to address emotional problems remained an area for improvement.
Authors
Sutton, LM; Geradts, J; Hamilton, EP; Havlin, KA; Kimmick, GG; Marcom, PK; Spector, NL; Watson, M; Rabin, DU; Bruno, TO; Noe, A; Miller, S; Subramaniam, C; Layton, S; Grichnik, K
MLA Citation
Sutton, Linda M., et al. “CHAMBER: A Regional Performance Improvement CME Initiative for Breast Cancer Health Care Providers.” J Natl Compr Canc Netw, vol. 13, no. 8, Aug. 2015, pp. 1005–11. Pubmed, doi:10.6004/jnccn.2015.0121.
URI
https://scholars.duke.edu/individual/pub1083601
PMID
26285246
Source
pubmed
Published In
J Natl Compr Canc Netw
Volume
13
Published Date
Start Page
1005
End Page
1011
DOI
10.6004/jnccn.2015.0121
Phase II study to evaluate the efficacy and safety of neoadjuvant lapatinib plus paclitaxel in patients with inflammatory breast cancer.
PURPOSE: We conducted a phase II, open-label, multicenter study to evaluate the efficacy, safety, and tolerability of daily lapatinib plus weekly paclitaxel in treatment-naïve patients with inflammatory breast cancer (IBC). PATIENTS AND METHODS: The primary end point was pathologic complete response (pCR). Secondary end points included combined clinical response rate (based on Response Evaluation Criteria in Solid Tumors (RECIST) criteria and clinically evaluable skin disease criteria). Patients were assigned to either cohort A (human epidermal growth factor receptor 2 [HER2] 2+ or 3+ by immunohistochemistry [IHC] or fluorescent in situ hybridization [FISH] -amplified +/- epidermal growth factor receptor [EGFR] expression) or cohort B (HER2-negative/EGFR-positive). A subpopulation of cohort A considered HER2-positive by the current definition of overexpression (3+ by IHC or FISH-amplified) was also analyzed. Patients received lapatinib at 1,500 mg/d for 14 days, then lapatinib at 1,500 mg/d plus weekly paclitaxel (80 mg/m(2)) for 12 weeks, followed by surgical resection or additional chemotherapy. RESULTS: Forty-nine women were enrolled (cohort A, n = 42; cohort B, n = 7). Cohort B was terminated because of slow accrual and lack of efficacy observed in IBC patients with HER2-negative/EGFR-positive tumors enrolled onto the parallel study, EGF103009. pCR occurred in 18.2% (95% CI, 5.2% to 40.3%) of cohort A patients. Combined clinical response rate was 78.6% (95% CI, 63.2% to 89.7%) in all cohort A patients and 78.1% (95% CI, 60.0% to 90.7%) in the HER2-positive subset. Common adverse events included diarrhea, rash, alopecia, and nausea (> 50% of patients in both cohorts). The incidence of grade 3 diarrhea was 55%. CONCLUSION: Lapatinib monotherapy for 14 days followed by lapatinib plus paclitaxel for 12 weeks provided clinical benefit in IBC patients with HER2-overexpressing tumors without unexpected toxicity.
Authors
Boussen, H; Cristofanilli, M; Zaks, T; DeSilvio, M; Salazar, V; Spector, N
MLA Citation
Boussen, Hamouda, et al. “Phase II study to evaluate the efficacy and safety of neoadjuvant lapatinib plus paclitaxel in patients with inflammatory breast cancer.” J Clin Oncol, vol. 28, no. 20, July 2010, pp. 3248–55. Pubmed, doi:10.1200/JCO.2009.21.8594.
URI
https://scholars.duke.edu/individual/pub799704
PMID
20530274
Source
pubmed
Published In
Journal of Clinical Oncology
Volume
28
Published Date
Start Page
3248
End Page
3255
DOI
10.1200/JCO.2009.21.8594
A model of acquired autoresistance to a potent ErbB2 tyrosine kinase inhibitor and a therapeutic strategy to prevent its onset in breast cancer.
The development of acquired resistance to ErbB2 tyrosine kinase inhibitors limits the clinical efficacy of this class of cancer therapeutics. Little is known about the mechanism(s) of acquired resistance to these agents. Here we establish a model of acquired resistance to N-{3-chloro-4-[(3-fluorobenzyl) oxy]phenyl}-6-[5-({[2 (methylsulfonyl)ethyl]amino}methyl)-2-furyl]-4-quinazolinamine (lapatinib), an inhibitor of ErbB2 and ErbB1 tyrosine kinases by chronically exposing lapatinib-sensitive ErbB2-overexpressing breast cancer cells to lapatinib, simulating the clinic where lapatinib is administered on a daily chronic basis. Analysis of baseline gene expression in acquired lapatinib-resistant and parental cells indicates estrogen receptor (ER) signaling involvement in the development of resistance. Using gene interference, we confirm that acquired resistance to lapatinib is mediated by a switch in cell survival dependence and regulation of a key antiapoptotic mediator from ErbB2 alone to codependence upon ER and ErbB2 rather than loss of ErbB2 expression or insensitivity of ErbB2 signaling to lapatinib. Increased ER signaling in response to lapatinib is enhanced by the activation of factors facilitating the transcriptional activity of ER, notably FOXO3a and caveolin-1. Importantly, we confirm that lapatinib induces ER signaling in tumor biopsies from patients with ErbB2-overexpressing breast cancers receiving lapatinib therapy. These findings provided the rationale for preventing the development of acquired resistance by simultaneously inhibiting both ER and ErbB2 signaling pathways. Establishing clinically relevant models of acquired resistance to ErbB2 kinase inhibitors will enhance therapeutic strategies to improve clinical outcomes for patients with ErbB2-overexpressing breast cancers.
Authors
Xia, W; Bacus, S; Hegde, P; Husain, I; Strum, J; Liu, L; Paulazzo, G; Lyass, L; Trusk, P; Hill, J; Harris, J; Spector, NL
MLA Citation
Xia, Wenle, et al. “A model of acquired autoresistance to a potent ErbB2 tyrosine kinase inhibitor and a therapeutic strategy to prevent its onset in breast cancer.” Proc Natl Acad Sci U S A, vol. 103, no. 20, May 2006, pp. 7795–800. Pubmed, doi:10.1073/pnas.0602468103.
URI
https://scholars.duke.edu/individual/pub697914
PMID
16682622
Source
pubmed
Published In
Proceedings of the National Academy of Sciences of the United States of America
Volume
103
Published Date
Start Page
7795
End Page
7800
DOI
10.1073/pnas.0602468103
Truncation of Sp1 transcription factor by myeloblastin in undifferentiated HL60 cells.
When HL60 cells are exposed to 1,25-dihydroxyvitamin D3 (1,25D3), they undergo changes approximating the phenotype of the monocyte. Little is known, however, about the regulation and the mechanisms of this transition. It was previously noted that DNA binding by the Sp1 transcription factor in nuclear extracts of HL60 cells is profoundly altered when these cells are induced to differentiate by 1,25D3. In the present study, we show that in untreated HL60 cells only a truncated, approximately 30-kDa Sp1 fragment, encompassing the C-terminal region, binds to the GC element-containing DNA. Full-length 105-kDa Sp1 protein cannot be detected in these cells, although reverse transriptase-polymerase chain reaction reveals the presence of both 5' and 3' ends of Sp1 mRNA. Following treatment with 10(7) M 1,25D3 for 96 hr or in cells made resistant to 1,25D3 or to 1-beta-D-arabinocytosine, the Sp1 protein can be demonstrated. After an exposure to purified myeloblastin, a serine protease, purified recombinant Sp1 protein and extracts of 1,25D3-treated cells show a pattern of DNA binding similar to the pattern seen using extracts of untreated HL60 cells, indicating that the Sp1 protein is a target for myeloblastin. Because myeloblastin is present in naive HL60 cells and is downregulated during their differentiation, inhibition of proteolysis of these transcription factors seems to provide a mechanism through which differentiating HL60 cells can acquire a new repertoire of gene expression, perhaps for the maintenance of the differentiated phenotype.
Authors
Rao, J; Zhang, F; Donnelly, RJ; Spector, NL; Studzinski, GP
MLA Citation
Rao, J., et al. “Truncation of Sp1 transcription factor by myeloblastin in undifferentiated HL60 cells.” J Cell Physiol, vol. 175, no. 2, May 1998, pp. 121–28. Pubmed, doi:10.1002/(SICI)1097-4652(199805)175:2<121::AID-JCP1>3.0.CO;2-Q.
URI
https://scholars.duke.edu/individual/pub1166680
PMID
9525470
Source
pubmed
Published In
Journal of Cellular Physiology
Volume
175
Published Date
Start Page
121
End Page
128
DOI
10.1002/(SICI)1097-4652(199805)175:2<121::AID-JCP1>3.0.CO;2-Q

Sandra Coates Associate Professor
Contact:
450 Research Drive, B354, Box 91004 Med Ctr, Durham, NC 27708