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:

Multitargeted Nanoparticles Deliver Synergistic Drugs across the Blood-Brain Barrier to Brain Metastases of Triple Negative Breast Cancer Cells and Tumor-Associated Macrophages.

Patients with brain metastases of triple negative breast cancer (TNBC) have a poor prognosis owing to the lack of targeted therapies, the aggressive nature of TNBC, and the presence of the blood-brain barrier (BBB) that blocks penetration of most drugs. Additionally, infiltration of tumor-associated macrophages (TAMs) promotes tumor progression. Here, a terpolymer-lipid hybrid nanoparticle (TPLN) system is designed with multiple targeting moieties to first undergo synchronized BBB crossing and then actively target TNBC cells and TAMs in microlesions of brain metastases. In vitro and in vivo studies demonstrate that covalently bound polysorbate 80 in the terpolymer enables the low-density lipoprotein receptor-mediated BBB crossing and TAM-targetability of the TPLN. Conjugation of cyclic internalizing peptide (iRGD) enhances cellular uptake, cytotoxicity, and drug delivery to brain metastases of integrin-overexpressing TNBC cells. iRGD-TPLN with coloaded doxorubicin (DOX) and mitomycin C (MMC) (iRGD-DMTPLN) exhibits higher efficacy in reducing metastatic burden and TAMs than nontargeted DMTPLN or a free DOX/MMC combination. iRGD-DMTPLN treatment reduces metastatic burden by 6-fold and 19-fold and increases host median survival by 1.3-fold and 1.6-fold compared to DMTPLN or free DOX/MMC treatments, respectively. These findings suggest that iRGD-DMTPLN is a promising multitargeted drug delivery system for the treatment of integrin-overexpressing brain metastases of TNBC.
Authors
Zhang, T; Lip, H; He, C; Cai, P; Wang, Z; Henderson, JT; Rauth, AM; Wu, XY
MLA Citation
Zhang, Tian, et al. “Multitargeted Nanoparticles Deliver Synergistic Drugs across the Blood-Brain Barrier to Brain Metastases of Triple Negative Breast Cancer Cells and Tumor-Associated Macrophages.Adv Healthc Mater, vol. 8, no. 18, Sept. 2019, p. e1900543. Pubmed, doi:10.1002/adhm.201900543.
URI
https://scholars.duke.edu/individual/pub1452390
PMID
31348614
Source
pubmed
Published In
Adv Healthc Mater
Volume
8
Published Date
Start Page
e1900543
DOI
10.1002/adhm.201900543

Sample Extraction and Simultaneous Chromatographic Quantitation of Doxorubicin and Mitomycin C Following Drug Combination Delivery in Nanoparticles to Tumor-bearing Mice.

Combination chemotherapy is frequently used in the clinic for cancer treatment; however, associated adverse effects to normal tissue may limit its therapeutic benefit. Nanoparticle-based drug combination has been shown to mitigate the problems encountered by free drug combination therapy. Our previous studies have shown that the combination of two anticancer drugs, doxorubicin (DOX) and mitomycin C (MMC), produced a synergistic effect against both murine and human breast cancer cells in vitro. DOX and MMC co-loaded polymer-lipid hybrid nanoparticles (DMPLN) bypassed various efflux transporter pumps that confer multidrug resistance and demonstrated enhanced efficacy in breast tumor models. Compared to conventional solution forms, such superior efficacy of DMPLN was attributed to the synchronized pharmacokinetics of DOX and MMC and increased intracellular drug bioavailability within tumor cells enabled by the nanocarrier PLN. To evaluate the pharmacokinetics and bio-distribution of co-administered DOX and MMC in both free solution and nanoparticle forms, a simple and efficient multi-drug analysis method using reverse-phase high performance liquid chromatography (HPLC) was developed. In contrast to previously reported methods that analyzed DOX or MMC individually in the plasma, this new HPLC method is able to simultaneously quantitate DOX, MMC and a major cardio-toxic DOX metabolite, doxorubicinol (DOXol), in various biological matrices (e.g., whole blood, breast tumor, and heart). A dual fluorescent and ultraviolet absorbent probe 4-methylumbelliferone (4-MU) was used as an internal standard (I.S.) for one-step detection of multiple drug analysis with different detection wavelengths. This method was successfully applied to determine the concentrations of DOX and MMC delivered by both nanoparticle and solution approaches in whole blood and various tissues in an orthotopic breast tumor murine model. The analytical method presented is a useful tool for pre-clinical analysis of nanoparticle-based delivery of drug combinations.
Authors
Zhang, RX; Zhang, T; Chen, K; Cheng, J; Lai, P; Rauth, AM; Pang, KS; Wu, XY
URI
https://scholars.duke.edu/individual/pub1452394
PMID
29053672
Source
pubmed
Published In
Journal of Visualized Experiments : Jove
Published Date
DOI
10.3791/56159

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