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:

3D Biology Signatures defined by Nanostring Max System

Administered By
Medicine, Medical Oncology
Awarded By
North Carolina Biotechnology Center
Role
Major User
Start Date
End Date

Regional Oncolytic Poliovirus Immunotherapy for Breast Cancer

Awarded By
Department of Defense
Role
Investigator
Start Date
End Date

Small Animal PET / CT Molecular Imaging

Administered By
Radiology, Nuclear Medicine
Awarded By
National Institutes of Health
Role
Major User
Start Date
End Date

Role of ErbB Receptor Signaling in Regulating Normal and Leukemic Stem Cell Fate

Administered By
Medicine, Hematologic Malignancies and Cellular Therapy
Awarded By
National Institutes of Health
Role
Collaborator
Start Date
End Date

Developing a HER3 Vaccine to Prevent Resistance to Endocrine Therapy

Awarded By
Department of Defense
Role
Co Investigator
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

Photo-activated psoralen binds the ErbB2 catalytic kinase domain, blocking ErbB2 signaling and triggering tumor cell apoptosis.

Photo-activation of psoralen with UVA irradiation, referred to as PUVA, is used in the treatment of proliferative skin disorders. The anti-proliferative effects of PUVA have been largely attributed to psoralen intercalation of DNA, which upon UV treatment, triggers the formation of interstrand DNA crosslinks (ICL) that inhibit transcription and DNA replication. Here, we show that PUVA exerts antitumor effects in models of human breast cancer that overexpress the ErbB2 receptor tyrosine kinase oncogene, through a new mechanism. Independent of ICL formation, the antitumor effects of PUVA in ErbB2+ breast cancer models can instead be mediated through inhibition of ErbB2 activation and signaling. Using a mass spectroscopy-based approach, we show for the first time that photo-activated 8MOP (8-methoxypsoralen) interacts with the ErbB2 catalytic autokinase domain. Furthermore, PUVA can reverse therapeutic resistance to lapatinib and other ErbB2 targeted therapies, including resistance mediated via expression of a phosphorylated, truncated form of ErbB2 (p85(ErbB2)) that is preferentially expressed in tumor cell nuclei. Current ErbB2 targeted therapies, small molecule kinase inhibitors or antibodies, do not block the phosphorylated, activated state of p85(ErbB2). Here we show that PUVA reduced p85(ErbB2) phosphorylation leading to tumor cell apoptosis. Thus, in addition to its effects on DNA and the formation of ICL, PUVA represents a novel ErbB2 targeted therapy for the treatment of ErbB2+ breast cancers, including those that have developed resistance to other ErbB2 targeted therapies.
Authors
Xia, W; Gooden, D; Liu, L; Zhao, S; Soderblom, EJ; Toone, EJ; Beyer, WF; Walder, H; Spector, NL
MLA Citation
Xia, Wenle, et al. “Photo-activated psoralen binds the ErbB2 catalytic kinase domain, blocking ErbB2 signaling and triggering tumor cell apoptosis.Plos One, vol. 9, no. 2, 2014, p. e88983. Pubmed, doi:10.1371/journal.pone.0088983.
URI
https://scholars.duke.edu/individual/pub1016044
PMID
24551203
Source
pubmed
Published In
Plos One
Volume
9
Published Date
Start Page
e88983
DOI
10.1371/journal.pone.0088983

A phase I and pharmacokinetic study of oral lapatinib administered once or twice daily in patients with solid malignancies.

PURPOSE: This study determined the range of tolerable doses, clinical safety, pharmacokinetics, and preliminary evidence of clinical activity following once or twice daily administration of lapatinib in patients with solid malignancies. EXPERIMENTAL DESIGN: Cancer patients (n = 81) received oral doses of lapatinib ranging from 175 to 1,800 mg once daily or 500 to 900 mg twice daily. Clinical assessments of safety and antitumor activity were recorded and blood was sampled for pharmacokinetic assessments. The effect of a low-fat meal on lapatinib pharmacokinetics was assessed in a subset of patients. RESULTS: Lapatinib was well tolerated, such that dose escalation was limited at 1,800 mg once daily only by pill burden. Twice-daily dosing was implemented to further explore tolerability, and was limited by diarrhea to 500 mg twice daily. The most commonly reported adverse events with once-daily dosing were diarrhea (48%), nausea (40%), rash (40%), and fatigue (38%) and with twice-daily dosing were diarrhea (85%), rash (54%), and nausea (34%). Lapatinib serum concentrations accumulated upon repeated dosing, increasing nearly in proportion with dose, and were significantly increased when dosed with food or administered twice daily. One patient with head and neck cancer achieved a confirmed complete response and 22 patients had stable disease of >or=8 weeks including three patients with stable disease of >10 months (renal, lung, and salivary gland cancers). CONCLUSION: Lapatinib was well tolerated following once and twice daily administration. Systemic exposure to lapatinib was dependent on the dose, duration and frequency of dosing, and prandial state. Clinical activity was observed.
Authors
Burris, HA; Taylor, CW; Jones, SF; Koch, KM; Versola, MJ; Arya, N; Fleming, RA; Smith, DA; Pandite, L; Spector, N; Wilding, G
MLA Citation
Burris, Howard A., et al. “A phase I and pharmacokinetic study of oral lapatinib administered once or twice daily in patients with solid malignancies.Clin Cancer Res, vol. 15, no. 21, Nov. 2009, pp. 6702–08. Pubmed, doi:10.1158/1078-0432.CCR-09-0369.
URI
https://scholars.duke.edu/individual/pub799705
PMID
19825948
Source
pubmed
Published In
Clinical Cancer Research : an Official Journal of the American Association for Cancer Research
Volume
15
Published Date
Start Page
6702
End Page
6708
DOI
10.1158/1078-0432.CCR-09-0369

Phase I safety, pharmacokinetics, and clinical activity study of lapatinib (GW572016), a reversible dual inhibitor of epidermal growth factor receptor tyrosine kinases, in heavily pretreated patients with metastatic carcinomas.

PURPOSE: This study (EGF10004) assessed the safety/tolerability, pharmacokinetics, and clinical activity of daily oral dosing with lapatinib (GW572016) in patients with ErbB1-expressing and/or ErbB2-overexpressing advanced-stage refractory solid tumors. PATIENTS AND METHODS: Heavily pretreated patients with ErbB1-expressing and/or ErbB2-overexpressing metastatic cancers were randomly assigned to one of five dose cohorts of lapatinib administered once daily. Pharmacokinetic samples were obtained on days 1 and 20. Clinical response was assessed every 8 weeks. RESULTS: Sixty-seven patients with metastatic solid tumors were treated with lapatinib. The most frequently reported drug-related adverse events were diarrhea (42%) and rash (31%). No grade 4 drug-related adverse events were reported. Five grade 3 drug-related toxicities (gastrointestinal events and rash) were experienced by four patients. Drug-related interstitial pneumonitis or cardiac dysfunction associated with other ErbB-targeted therapies was not reported. Four patients with trastuzumab-resistant metastatic breast cancer-two of whom were classified as having inflammatory breast cancer-had partial responses (PRs). Twenty-four patients with various other carcinomas experienced stable disease, of whom 10 received lapatinib for > or = 6 months. The relationships between lapatinib dose or serum concentration and clinical response could not be adequately characterized due to the limited response data. The incidence of diarrhea increased with increasing dose, whereas the incidence of rash was not related to dose. CONCLUSION: Lapatinib was well tolerated at doses ranging from 500 to 1,600 mg once daily. Clinical activity was observed in heavily pretreated patients with ErbB1-expressing and/or ErbB2-overexpressing metastatic cancers, including four PRs in patients with trastuzumab-resistant breast cancers and prolonged stable disease in 10 patients.
Authors
Burris, HA; Hurwitz, HI; Dees, EC; Dowlati, A; Blackwell, KL; O'Neil, B; Marcom, PK; Ellis, MJ; Overmoyer, B; Jones, SF; Harris, JL; Smith, DA; Koch, KM; Stead, A; Mangum, S; Spector, NL
URI
https://scholars.duke.edu/individual/pub680866
PMID
15955900
Source
pubmed
Published In
Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology
Volume
23
Published Date
Start Page
5305
End Page
5313
DOI
10.1200/JCO.2005.16.584

Regulation of the 28 kDa heat shock protein by retinoic acid during differentiation of human leukemic HL-60 cells

Dysregulation of hematopoietic cellular differentiation contributes to leukemogenesis. Unfortunately, relatively little is known about how cell differentiation is regulated. Considering that heat shock proteins (hsp) and specifically the small hsps have been increasingly linked to growth regulation, we sought to determine whether the mammalian small hsp (hsp28) is a growth-regulatory candidate during hematopoietic cell differentiation. Because of its effects on cell growth and differentiation and its increasing clinical use as a differentiating agent, we examined the effect of retinoic acid (RA) on hsp28 during differentiation of the human leukemic HL-60 cell line. Although hsp28 was constitutively expressed at low levels in untreated HL-60 cells, steady state hsp28 protein increased transiently, concomitant with the onset of G1 cell cycle arrest. Furthermore, hsp28 phosphorylation transiently increased within one hour following treatment with RA. Interestingly, in contrast to other differentiating agents the induction of hsp28 by RA was post-transcriptionally mediated with hsp28 protein and mRNA being discordantly regulated. These observations underscore the complex regulation of hsp28 by RA during granulocytic differentiation of human leukemic cells and indicate hsp28 as an intermediary in the pathway through which retinoids exert their growth and differentiative effects.
Authors
MLA Citation
Spector, N. L. “Regulation of the 28 kDa heat shock protein by retinoic acid during differentiation of human leukemic HL-60 cells.” Febs Letters, vol. 337, no. 2, 1994, pp. 184–88. Scival, doi:10.1016/0014-5793(94)80270-X.
URI
https://scholars.duke.edu/individual/pub799721
Source
scival
Published In
Febs Letters
Volume
337
Published Date
Start Page
184
End Page
188
DOI
10.1016/0014-5793(94)80270-X