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

Pertuzumab protects the achilles' heel of trastuzumab--emtansine.

Trastuzumab emtansine (T-DM1) represents a significant advancement in the treatment of HER2(+) breast cancers. Its clinical efficacy however will be limited by the development of therapeutic resistance. In this report, the HER3 ligand neuregulin is shown to mediate T-DM1 resistance, which was overcome by administration of pertuzumab, a steric inhibitor of HER2 dimerization.
Authors
Gwin, WR; Spector, NL
MLA Citation
Gwin, William R., and Neil L. Spector. “Pertuzumab protects the achilles' heel of trastuzumab--emtansine.Clin Cancer Res, vol. 20, no. 2, Jan. 2014, pp. 278–80. Pubmed, doi:10.1158/1078-0432.CCR-13-2626.
URI
https://scholars.duke.edu/individual/pub1000509
PMID
24240115
Source
pubmed
Published In
Clinical Cancer Research : an Official Journal of the American Association for Cancer Research
Volume
20
Published Date
Start Page
278
End Page
280
DOI
10.1158/1078-0432.CCR-13-2626

Resistance to ErbB2 tyrosine kinase inhibitors in breast cancer is mediated by calcium-dependent activation of RelA.

The widespread clinical use of therapies targeting the ErbB2 receptor tyrosine kinase oncogene represents a significant advance in breast cancer treatment. However, the development of therapeutic resistance represents a dilemma limiting their clinical efficacy, particularly small-molecule tyrosine kinase inhibitors that block ErbB2 autophosphorylation and activation. Here, we show that lapatinib (GW572016), a highly selective, small-molecule inhibitor of the ErbB2 and epidermal growth factor receptor tyrosine kinases, which was recently approved for the treatment of advanced-stage ErbB2(+) breast cancer, unexpectedly triggered a cytoprotective stress response in ErbB2(+) breast cancer cell lines, which was mediated by the calcium-dependent activation of RelA, the prosurvival subunit of NF-kappaB. Abrogation of lapatinib-induced RelA activation using either small interfering RNA constructs or an intracellular calcium chelator enhanced the apoptotic effects of lapatinib in parental ErbB2(+) breast cancer cells and overcame therapeutic resistance to lapatinib in ErbB2(+) breast cancer lines that had been rendered resistant to lapatinib through chronic exposure to the drug, mimicking the clinical setting. In addition, analysis of changes in phospho-RelA expression in sequential clinical biopsies from ErbB2(+) breast cancers treated with lapatinib monotherapy revealed marginally statistically significant differences between responders and nonresponders, which was consistent with our preclinical findings. Elucidating the regulation of RelA by lapatinib in ErbB2(+) breast cancers, and showing its role in the development of therapeutic resistance to lapatinib, identifies another therapeutic target to overcome or prevent the onset of resistance to lapatinib in some women with ErbB2(+) breast cancers.
Authors
Xia, W; Bacus, S; Husain, I; Liu, L; Zhao, S; Liu, Z; Moseley, MA; Thompson, JW; Chen, FL; Koch, KM; Spector, NL
MLA Citation
Xia, Wenle, et al. “Resistance to ErbB2 tyrosine kinase inhibitors in breast cancer is mediated by calcium-dependent activation of RelA.Mol Cancer Ther, vol. 9, no. 2, Feb. 2010, pp. 292–99. Pubmed, doi:10.1158/1535-7163.MCT-09-1041.
URI
https://scholars.duke.edu/individual/pub789426
PMID
20124457
Source
pubmed
Published In
Mol Cancer Ther
Volume
9
Published Date
Start Page
292
End Page
299
DOI
10.1158/1535-7163.MCT-09-1041

Rational development of targeted cancer therapies using biomarkers

As the complex network of signalling pathways involved in regulating tumor cell growth and survival is unraveled, tractable targets for therapeutic drug development have been identified. Questions regarding the best approach towards developing these targeted therapies remain [eg, what is the best strategy for (i) selecting doses, (ii) identifying target patient populations for clinical trials, and (iii) designing combination therapies based on scientific rationale]. Since these agents exert biological and clinical effects that are generally distinct from traditional cytotoxic agents, a different paradigm for their development has been suggested. Here we will discuss how incorporation of biomaker analysis in early-phase clinical trials can provide valuable information to guide further development of targeted therapies.
Authors
Bacus, S; Yarden, Y; Xia, W; Spector, NL
MLA Citation
Bacus, S., et al. “Rational development of targeted cancer therapies using biomarkers.” Laboratory Medicine, vol. 37, no. 8, Jan. 2006, pp. 482–89. Scopus, doi:10.1309/C0YYYW2L55EQ90CN.
URI
https://scholars.duke.edu/individual/pub799711
Source
scopus
Published In
Laboratory Medicine
Volume
37
Published Date
Start Page
482
End Page
489
DOI
10.1309/C0YYYW2L55EQ90CN

28-kDa mammalian heat shock protein, a novel substrate of a growth regulatory protease involved in differentiation of human leukemia cells.

Because of their differentiating effects in neoplastic cells in vitro, the use of retinoids in the treatment of various malignant and premalignant conditions is under investigation. To date, signal transduction pathways involved in retinoid-induced differentiation remain poorly understood. Differentiation of HL-60 cells by all-trans-retinoic acid (tRA) is directly mediated by down-regulation of the serine protease myeloblastin (mbn). In this report, we investigate the possibility that the 28-kDa heat shock protein (hsp28), previously linked to differentiation of normal and neoplastic cells including HL-60, may be regulated by mbn. Using NB4 promyelocytic leukemic cells as a differentiative model, we show that tRA induces initial suppression and subsequent up-regulation of hsp28 protein, mirroring tRA-induced changes in mbn protein. The progressive reduction in hsp28 mRNA levels in response to tRA suggests that changes in hsp28 protein levels might be posttranscriptionally mediated, raising the possibility that hsp28 may be targeted by mbn. To address this, we developed an assay using purified mbn and recombinant hsp28 and now show that hsp28 is hydrolyzed by mbn but not its homologue, human neutrophil elastase. Moreover, mbn does not indiscriminately hydrolyze other proteins. Identifying hsp28 as a substrate of mbn strongly suggests that hsp28 may be a key component of the tRA signaling pathway involved in regulating cell differentiation.
Authors
Spector, NL; Hardy, L; Ryan, C; Miller, WH; Humes, JL; Nadler, LM; Luedke, E
MLA Citation
Spector, N. L., et al. “28-kDa mammalian heat shock protein, a novel substrate of a growth regulatory protease involved in differentiation of human leukemia cells.J Biol Chem, vol. 270, no. 3, Jan. 1995, pp. 1003–06. Pubmed, doi:10.1074/jbc.270.3.1003.
URI
https://scholars.duke.edu/individual/pub799717
PMID
7836350
Source
pubmed
Published In
The Journal of Biological Chemistry
Volume
270
Published Date
Start Page
1003
End Page
1006
DOI
10.1074/jbc.270.3.1003