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
Identification of an allosteric small-molecule inhibitor selective for the inducible form of heat shock protein 70.
Inducible Hsp70 (Hsp70i) is overexpressed in a wide spectrum of human tumors, and its expression correlates with metastasis, poor outcomes, and resistance to chemotherapy in patients. Identification of small-molecule inhibitors selective for Hsp70i could provide new therapeutic tools for cancer treatment. In this work, we used fluorescence-linked enzyme chemoproteomic strategy (FLECS) to identify HS-72, an allosteric inhibitor selective for Hsp70i. HS-72 displays the hallmarks of Hsp70 inhibition in cells, promoting substrate protein degradation and growth inhibition. Importantly, HS-72 is selective for Hsp70i over the closely related constitutively active Hsc70. Studies with purified protein show HS-72 acts as an allosteric inhibitor, reducing ATP affinity. In vivo HS-72 is well-tolerated, showing bioavailability and efficacy, inhibiting tumor growth and promoting survival in a HER2+ model of breast cancer. The HS-72 scaffold is amenable to resynthesis and iteration, suggesting an ideal starting point for a new generation of anticancer therapeutics targeting Hsp70i.
Authors
Howe, MK; Bodoor, K; Carlson, DA; Hughes, PF; Alwarawrah, Y; Loiselle, DR; Jaeger, AM; Darr, DB; Jordan, JL; Hunter, LM; Molzberger, ET; Gobillot, TA; Thiele, DJ; Brodsky, JL; Spector, NL; Haystead, TAJ
MLA Citation
Howe, Matthew K., et al. “Identification of an allosteric small-molecule inhibitor selective for the inducible form of heat shock protein 70.” Chem Biol, vol. 21, no. 12, Dec. 2014, pp. 1648–59. Pubmed, doi:10.1016/j.chembiol.2014.10.016.
URI
https://scholars.duke.edu/individual/pub1054548
PMID
25500222
Source
pubmed
Published In
Chemistry & Biology
Volume
21
Published Date
Start Page
1648
End Page
1659
DOI
10.1016/j.chembiol.2014.10.016
An adenoviral vaccine encoding full-length inactivated human Her2 exhibits potent immunogenicty and enhanced therapeutic efficacy without oncogenicity.
PURPOSE: Overexpression of the breast cancer oncogene HER2 correlates with poor survival. Current HER2-directed therapies confer limited clinical benefits and most patients experience progressive disease. Because refractory tumors remain strongly HER2+, vaccine approaches targeting HER2 have therapeutic potential, but wild type (wt) HER2 cannot safely be delivered in immunogenic viral vectors because it is a potent oncogene. We designed and tested several HER2 vaccines devoid of oncogenic activity to develop a safe vaccine for clinical use. EXPERIMENTAL DESIGN: We created recombinant adenoviral vectors expressing the extracellular domain of HER2 (Ad-HER2-ECD), ECD plus the transmembrane domain (Ad-HER2-ECD-TM), and full-length HER2 inactivated for kinase function (Ad-HER2-ki), and determined their immunogenicity and antitumor effect in wild type (WT) and HER2-tolerant mice. To assess their safety, we compared their effect on the cellular transcriptome, cell proliferation, anchorage-dependent growth, and transformation potential in vivo. RESULTS: Ad-HER2-ki was the most immunogenic vector in WT animals, retained immunogenicity in HER2-transgenic tolerant animals, and showed strong therapeutic efficacy in treatment models. Despite being highly expressed, HER2-ki protein was not phosphorylated and did not produce an oncogenic gene signature in primary human cells. Moreover, in contrast to HER2-wt, cells overexpressing HER2-ki were less proliferative, displayed less anchorage-independent growth, and were not transformed in vivo. CONCLUSIONS: Vaccination with mutationally inactivated, nononcogenic Ad-HER2-ki results in robust polyclonal immune responses to HER2 in tolerant models, which translates into strong and effective antitumor responses in vivo. Ad-HER2-ki is thus a safe and promising vaccine for evaluation in clinical trials.
Authors
Hartman, ZC; Wei, J; Osada, T; Glass, O; Lei, G; Yang, X-Y; Peplinski, S; Kim, D-W; Xia, W; Spector, N; Marks, J; Barry, W; Hobeika, A; Devi, G; Amalfitano, A; Morse, MA; Lyerly, HK; Clay, TM
MLA Citation
Hartman, Zachary C., et al. “An adenoviral vaccine encoding full-length inactivated human Her2 exhibits potent immunogenicty and enhanced therapeutic efficacy without oncogenicity.” Clin Cancer Res, vol. 16, no. 5, Mar. 2010, pp. 1466–77. Pubmed, doi:10.1158/1078-0432.CCR-09-2549.
URI
https://scholars.duke.edu/individual/pub726604
PMID
20179231
Source
pubmed
Published In
Clinical Cancer Research
Volume
16
Published Date
Start Page
1466
End Page
1477
DOI
10.1158/1078-0432.CCR-09-2549
Delivery of a healthy baby after first-trimester maternal exposure to lapatinib
We report the case of a woman who conceived while being treated on a phase I clincal trial with lapatinib, a dual inhibitor of epidermal growth factor receptor (EGFR) and HER2/neu, for metastatic breast cancer. Despite approximately 11 weeks of exposure to lapatinib in the first and second trimesters, the pregnancy was uncomplicated and resulted in the delivery of a healthy baby. Although concomitant cancer and pregnancy is relatively rare, the increasing use of biologic agents among fertile women - sometimes for as long as a year in the adjuvant setting - increases the probability that some women will conceive while taking a growth factor pathway inhibitor. As with systemic chemotherapy given during pregnancy, there exists the potential for teratogenicity or fetal demise from exposure of the developing embryo to inhibitors of EGFR and HER2/neu. Despite the positive outcome of this case, continued caution is warranted with the use of EGFR and HER2/neu inhibitors in pregnancy.
Authors
Kelly, H; Graham, M; Humes, E; Dorflinger, LJ; Boggess, KA; O'Neil, BH; Harris, J; Spector, NL; Dees, EC
MLA Citation
Kelly, H., et al. “Delivery of a healthy baby after first-trimester maternal exposure to lapatinib.” Clinical Breast Cancer, vol. 7, no. 4, Jan. 2006, pp. 339–41. Scopus, doi:10.3816/CBC.2006.n.048.
URI
https://scholars.duke.edu/individual/pub799710
Source
scopus
Published In
Clinical Breast Cancer
Volume
7
Published Date
Start Page
339
End Page
341
DOI
10.3816/CBC.2006.n.048
Activation signals regulate heat shock transcription factor 1 in human B lymphocytes.
We previously showed that the ability of human B lymphocytes to elicit a cytoprotective heat shock response when confronted by heat or other stresses was dependent upon the state of cell activation. This was unexpected, considering the highly conserved nature of the heat shock response and the widely held belief that all nonmutated mature cells were capable of eliciting a heat shock response when stressed. To elucidate the mechanism by which activation primes B cells to respond to stresses, we examined heat shock transcription factor 1 (hHSF1) in B cells since this factor appears to be solely responsible for stress-induced transcription of heat shock genes in human cells. In the current report, we show that hHSF1-DNA binding complexes are undetectable in extracts of unactivated B cells. In fact, hHSF1 protein is not constitutively expressed in unactivated B cells, nor is its synthesis stress-inducible. However, following activation, hHSF1 can be found in either a transcriptionally active or an inactive state, depending upon whether the cell has been stressed or not. Thus, activation pathways play an important role in enabling B cells to survive and function properly in the context of physiologic stresses by regulating hHSF1.
Authors
Hardy, L; Goodman, M; Vasquez, A; Chauhan, D; Anderson, KC; Voellmy, R; Spector, NL
MLA Citation
Hardy, L., et al. “Activation signals regulate heat shock transcription factor 1 in human B lymphocytes.” J Cell Physiol, vol. 170, no. 3, Mar. 1997, pp. 235–40. Pubmed, doi:10.1002/(SICI)1097-4652(199703)170:3<235::AID-JCP3>3.0.CO;2-P.
URI
https://scholars.duke.edu/individual/pub1166679
PMID
9066779
Source
pubmed
Published In
Journal of Cellular Physiology
Volume
170
Published Date
Start Page
235
End Page
240
DOI
10.1002/(SICI)1097-4652(199703)170:3<235::AID-JCP3>3.0.CO;2-P

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