Tian Zhang

Positions:

Assistant Professor of Medicine

Medicine, Medical Oncology
School of Medicine

Member of the Duke Cancer Institute

Duke Cancer Institute
School of Medicine

Education:

M.D. 2009

Harvard Medical School

M.H.S. 2019

Duke University School of Medicine

Internal Medicine Residency, Medicine

Duke University School of Medicine

Fellowship in Hematology-Oncology, Medicine

Duke University School of Medicine

Grants:

Duke-UNC-Wash U Partnership for Early Phase Clinical Trials in Cancer

Administered By
Medicine, Medical Oncology
Awarded By
National Institutes of Health
Role
Significant Contributor
Start Date
End Date

Defining the Relevant Immune Checkpoints Expressed on Metastatic Prostate Cancer Circulating Tumor Cells

Administered By
Duke Cancer Institute
Awarded By
Janssen Research & Development, LLC
Role
Co-Principal Investigator
Start Date
End Date

Conditional lethality of copper and disulfiram as a therapeutic modality for prostate cancer

Administered By
Medicine, Medical Oncology
Awarded By
V Foundation for Cancer Research
Role
Principal Investigator
Start Date
End Date

A Phase III, Randomized, Double-Blind, Placebo-Controlled Clinical Trial of Pembrolizumab (MK-3475) as Monotherapy in the Adjuvant Treatment of Renal Cell Carcinoma Post Nephrectomy (KEYNOTE-564)

Administered By
Duke Cancer Institute
Awarded By
Merck
Role
Principal Investigator
Start Date
End Date

A Salvage Trial of AR Inhibition with ADT and Apalutamide with Docetaxel followed by Radiation Therapy in Men with PSA Recurrent Prostate Cancer after Radical Prostatectomy (¿STARTAR¿)

Administered By
Duke Cancer Institute
Awarded By
Janssen Pharmaceutica, Inc.
Role
Principal Investigator
Start Date
End Date

Publications:

Phase I/II study of LAG525 ± spartalizumab (PDR001) in patients (pts) with advanced malignancies.

Authors
Hong, DS; Schoffski, P; Calvo, A; Sarantopoulos, J; Ochoa De Olza, M; Carvajal, RD; Prawira, A; Kyi, C; Esaki, T; Akerley, WL; De Braud, FG; Hui, R; Zhang, T; Soo, RA; Maur, M; Weickhardt, AJ; Roy Chowdhury, N; Sabatos-Peyton, C; Kwak, EL; Tan, DS-W
MLA Citation
Hong, David S., et al. “Phase I/II study of LAG525 ± spartalizumab (PDR001) in patients (pts) with advanced malignancies.Journal of Clinical Oncology, vol. 36, no. 15_suppl, American Society of Clinical Oncology (ASCO), 2018, pp. 3012–3012. Crossref, doi:10.1200/jco.2018.36.15_suppl.3012.
URI
https://scholars.duke.edu/individual/pub1451500
Source
crossref
Published In
Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology
Volume
36
Published Date
Start Page
3012
End Page
3012
DOI
10.1200/jco.2018.36.15_suppl.3012

A phase 1 study evaluating the safety, pharmacology and preliminary activity of MM-310 in patients with solid tumors.

Authors
Ernstoff, MS; Ma, WW; Tsai, FY-C; Munster, PN; Zhang, T; Kamoun, W; Pipas, JM; Chen, S; Santillana, S; Askoxylakis, V
MLA Citation
Ernstoff, Marc S., et al. “A phase 1 study evaluating the safety, pharmacology and preliminary activity of MM-310 in patients with solid tumors.Journal of Clinical Oncology, vol. 36, no. 15_suppl, American Society of Clinical Oncology (ASCO), 2018, pp. TPS2604–TPS2604. Crossref, doi:10.1200/jco.2018.36.15_suppl.tps2604.
URI
https://scholars.duke.edu/individual/pub1452967
Source
crossref
Published In
Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology
Volume
36
Published Date
Start Page
TPS2604
End Page
TPS2604
DOI
10.1200/jco.2018.36.15_suppl.tps2604

Importance of integrating nanotechnology with pharmacology and physiology for innovative drug delivery and therapy - an illustration with firsthand examples.

Nanotechnology has been applied extensively in drug delivery to improve the therapeutic outcomes of various diseases. Tremendous efforts have been focused on the development of novel nanoparticles and delineation of the physicochemical properties of nanoparticles in relation to their biological fate and functions. However, in the design and evaluation of these nanotechnology-based drug delivery systems, the pharmacology of delivered drugs and the (patho-)physiology of the host have received less attention. In this review, we discuss important pharmacological mechanisms, physiological characteristics, and pathological factors that have been integrated into the design of nanotechnology-enabled drug delivery systems and therapies. Firsthand examples are presented to illustrate the principles and advantages of such integrative design strategies for cancer treatment by exploiting 1) intracellular synergistic interactions of drug-drug and drug-nanomaterial combinations to overcome multidrug-resistant cancer, 2) the blood flow direction of the circulatory system to maximize drug delivery to the tumor neovasculature and cells overexpressing integrin receptors for lung metastases, 3) endogenous lipoproteins to decorate nanocarriers and transport them across the blood-brain barrier for brain metastases, and 4) distinct pathological factors in the tumor microenvironment to develop pH- and oxidative stress-responsive hybrid manganese dioxide nanoparticles for enhanced radiotherapy. Regarding the application in diabetes management, a nanotechnology-enabled closed-loop insulin delivery system was devised to provide dynamic insulin release at a physiologically relevant time scale and glucose levels. These examples, together with other research results, suggest that utilization of the interplay of pharmacology, (patho-)physiology and nanotechnology is a facile approach to develop innovative drug delivery systems and therapies with high efficiency and translational potential.
Authors
Zhang, RX; Li, J; Zhang, T; Amini, MA; He, C; Lu, B; Ahmed, T; Lip, H; Rauth, AM; Wu, XY
MLA Citation
Zhang, Rui Xue, et al. “Importance of integrating nanotechnology with pharmacology and physiology for innovative drug delivery and therapy - an illustration with firsthand examples.Acta Pharmacol Sin, vol. 39, no. 5, May 2018, pp. 825–44. Pubmed, doi:10.1038/aps.2018.33.
URI
https://scholars.duke.edu/individual/pub1452393
PMID
29698389
Source
pubmed
Published In
Acta Pharmacol Sin
Volume
39
Published Date
Start Page
825
End Page
844
DOI
10.1038/aps.2018.33

Polymer-lipid hybrid nanoparticles synchronize pharmacokinetics of co-encapsulated doxorubicin-mitomycin C and enable their spatiotemporal co-delivery and local bioavailability in breast tumor.

UNLABELLED: Effective combination chemotherapy requires the delivery of drugs of synergism to tumor sites while sparing normal tissues. Herein we investigated whether coencapsulation of doxorubicin and mitomycin C within polymer-lipid hybrid nanoparticles (DMPLN) achieved this goal via ratiometric drugs in an orthotopic murine breast tumor model with nanocarrier-modified biodistribution, pharmacokinetics, local bioavailability and toxicity. Fluorescence imaging revealed quickened and extended tumor uptake but reduced cardiac accumulation of DMPLN. Quantitative drug analysis demonstrated prolonged systemic circulation, increased tumor accumulation and sustained synergistic ratios of doxorubicin and mitomycin C delivered by DMPLN over 24h. Higher levels of tumor cell apoptosis and reduced organ toxicity were obtained with DMPLN compared to free drug cocktails. DMPLN released DOX in tumors more efficiently than that from liposomal doxorubicin, as evidenced by a higher extent of the metabolite, doxorubicinol. These findings substantiate the importance of rational design of nanoparticles for synergistic drug combination therapy. FROM THE CLINICAL EDITOR: The treatment of cancer usually involves using combination chemotherapeutic agents. In adopting a nanomedicine approach, one can in theory design combination therapy consisting of drugs of synergistic activities, with the aim to target tumor specifically while minimizing systemic toxicity. The authors in this study provided evidence for this rational design by co-encapsulation of doxorubicin and mitomycin C within polymer-lipid hybrid nanoparticles (DMPLN) in a breast cancer model.
Authors
Zhang, RX; Cai, P; Zhang, T; Chen, K; Li, J; Cheng, J; Pang, KS; Adissu, HA; Rauth, AM; Wu, XY
MLA Citation
URI
https://scholars.duke.edu/individual/pub1452397
PMID
26772427
Source
pubmed
Published In
Nanomedicine
Volume
12
Published Date
Start Page
1279
End Page
1290
DOI
10.1016/j.nano.2015.12.383

In Situ Proapoptotic Peptide-Generating Rapeseed Protein-Based Nanocomplexes Synergize Chemotherapy for Cathepsin-B Overexpressing Breast Cancer.

Intracellular activation of nanomaterials within cancer cells presents a powerful means to enhance anticancer specificity and efficacy. In light of upregulated lysosomal protease cathepsin-B (CathB) in many types of invasive cancer cells, herein, we exploit CathB-catalyzed biodegradation of acetylated rapeseed protein isolate (ARPI) to design polymer-drug nanocomplexes that can produce proapoptotic peptides in situ and synergize chemotherapy. ARPI forms nanocomplexes with chitosan (CS) and anticancer drug doxorubicin (DOX) [DOX-ARPI/CS nanoparticles (NPs)] by ionic self-assembly. The dual acidic pH- and CathB-responsive properties of the nanocomplexes and CathB-catalyzed biodegradation of ARPI enable efficient lysosomal escape and nuclei trafficking of released DOX, resulting in elevated cytotoxicity in CathB-overexpressing breast cancer cells. The ARPI-derived bioactive peptides exhibit synergistic anticancer effect with DOX by regulating pro- and antiapoptotic-relevant proteins ( p53, Bax, Bcl-2, pro-caspase-3) at mitochondria. In an orthotopic breast tumor model of CathB-overexpressing breast cancer, DOX-ARPI/CS NPs remarkably inhibit tumor growth, enhance tumor cell apoptosis and prolong host survival without eliciting any systemic toxicity. These results suggest that exploitation of multifunctional biomaterials to specifically produce anticancer agents inside cancer cells and trigger drug release to the subcellular target sites is a promising strategy for designing effective synergistic nanomedicines with minimal off-target toxicity.
Authors
Wang, Z; Zhang, RX; Zhang, T; He, C; He, R; Ju, X; Wu, XY
MLA Citation
Wang, Zhigao, et al. “In Situ Proapoptotic Peptide-Generating Rapeseed Protein-Based Nanocomplexes Synergize Chemotherapy for Cathepsin-B Overexpressing Breast Cancer.Acs Appl Mater Interfaces, vol. 10, no. 48, Dec. 2018, pp. 41056–69. Pubmed, doi:10.1021/acsami.8b14001.
URI
https://scholars.duke.edu/individual/pub1452392
PMID
30387987
Source
pubmed
Published In
Acs Appl Mater Interfaces
Volume
10
Published Date
Start Page
41056
End Page
41069
DOI
10.1021/acsami.8b14001