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

Internal Medicine Residency, Medicine

Duke University School of Medicine

Fellowship in Hematology-Oncology, Medicine

Duke University School of Medicine

Grants:

CTC-Immune Checkpoints

Administered By
Duke Cancer Institute
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
Co 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
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
Role
Principal Investigator
Start Date
End Date

Merrimack MM-310-01-01-01

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

Publications:

Precision Medicine Approaches When Prostate Cancer Akts Up.

Ipatasertib combined with abiraterone in PTEN-null prostate cancer improved progression-free survival in a randomized phase II study of patients with metastatic castration-resistant prostate cancer (mCRPC), providing clinical evidence of reciprocal activation between the Akt and androgen receptor (AR) pathways. These data revive the rationale for targeting PTEN loss in prostate cancer.See related article by de Bono et al., p. 928.
Authors
Zhang, T; George, DJ; Armstrong, AJ
MLA Citation
Zhang, Tian, et al. “Precision Medicine Approaches When Prostate Cancer Akts Up..” Clin Cancer Res, vol. 25, no. 3, Feb. 2019, pp. 901–03. Pubmed, doi:10.1158/1078-0432.CCR-18-2491.
URI
https://scholars.duke.edu/individual/pub1350434
PMID
30206162
Source
pubmed
Published In
Clinical Cancer Research : an Official Journal of the American Association for Cancer Research
Volume
25
Published Date
Start Page
901
End Page
903
DOI
10.1158/1078-0432.CCR-18-2491

Acute Myeloid Leukemia After Olaparib Treatment in Metastatic Castration-Resistant Prostate Cancer.

Authors
Zhu, J; Tucker, M; Wang, E; Grossman, JS; Armstrong, AJ; George, DJ; Zhang, T
MLA Citation
Zhu, Jason, et al. “Acute Myeloid Leukemia After Olaparib Treatment in Metastatic Castration-Resistant Prostate Cancer..” Clin Genitourin Cancer, vol. 15, no. 6, Dec. 2017, pp. e1137–41. Pubmed, doi:10.1016/j.clgc.2017.07.005.
URI
https://scholars.duke.edu/individual/pub1265711
PMID
28780018
Source
pubmed
Published In
Clin Genitourin Cancer
Volume
15
Published Date
Start Page
e1137
End Page
e1141
DOI
10.1016/j.clgc.2017.07.005

Snail promotes resistance to enzalutamide through regulation of androgen receptor activity in prostate cancer.

Treatment with androgen-targeted therapies can induce upregulation of epithelial plasticity pathways. Epithelial plasticity is known to be important for metastatic dissemination and therapeutic resistance. The goal of this study is to elucidate the functional consequence of induced epithelial plasticity on AR regulation during disease progression to identify factors important for treatment-resistant and metastatic prostate cancer. We pinpoint the epithelial plasticity transcription factor, Snail, at the nexus of enzalutamide resistance and prostate cancer metastasis both in preclinical models of prostate cancer and in patients. In patients, Snail expression is associated with Gleason 9-10 high-risk disease and is strongly overexpressed in metastases as compared to localized prostate cancer. Snail expression is also elevated in enzalutamide-resistant prostate cancer cells compared to enzalutamide-sensitive cells, and downregulation of Snail re-sensitizes enzalutamide-resistant cells to enzalutamide. While activation of Snail increases migration and invasion, it is also capable of promoting enzalutamide resistance in enzalutamide-sensitive cells. This Snail-mediated enzalutamide resistance is a consequence of increased full-length AR and AR-V7 expression and nuclear localization. Downregulation of either full-length AR or AR-V7 re-sensitizes cells to enzalutamide in the presence of Snail, thus connecting Snail-induced enzalutamide resistance directly to AR biology. Finally, we demonstrate that Snail is capable of mediating-resistance through AR even in the absence of AR-V7. These findings imply that increased Snail expression during progression to metastatic disease may prime cells for resistance to AR-targeted therapies by promoting AR activity in prostate cancer.
Authors
Ware, KE; Somarelli, JA; Schaeffer, D; Li, J; Zhang, T; Park, S; Patierno, SR; Freedman, J; Foo, W-C; Garcia-Blanco, MA; Armstrong, AJ
MLA Citation
Ware, Kathryn E., et al. “Snail promotes resistance to enzalutamide through regulation of androgen receptor activity in prostate cancer..” Oncotarget, vol. 7, no. 31, Aug. 2016, pp. 50507–21. Pubmed, doi:10.18632/oncotarget.10476.
URI
https://scholars.duke.edu/individual/pub1137904
PMID
27409172
Source
pubmed
Published In
Oncotarget
Volume
7
Published Date
Start Page
50507
End Page
50521
DOI
10.18632/oncotarget.10476

Is advanced imaging in early-stage breast cancer ever warranted? Exploring benchmarks for an ASCO Choosing Wisely quality measure.

Authors
Zhang, T; Power, S; Marcom, PK; Kamal, A
MLA Citation
Zhang, Tian, et al. “Is advanced imaging in early-stage breast cancer ever warranted? Exploring benchmarks for an ASCO Choosing Wisely quality measure..” Journal of Clinical Oncology, vol. 32, no. 15_suppl, American Society of Clinical Oncology (ASCO), 2014, pp. 6503–6503. Crossref, doi:10.1200/jco.2014.32.15_suppl.6503.
URI
https://scholars.duke.edu/individual/pub1085500
Source
crossref
Published In
Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology
Volume
32
Published Date
Start Page
6503
End Page
6503
DOI
10.1200/jco.2014.32.15_suppl.6503

Outcomes in phase II trials of metastatic breast cancer: Where is the bar?

2590 Background: Phase II trials serve to provide safety and efficacy data for evaluating novel interventions that may be selected for large Phase III trials. To help define benchmarks for efficacy, we evaluated outcomes of all recently published metastatic breast cancer Phase II trials (MBP2). METHODS: All English language MBP2 published from June 2005 through June 2010 were identified by Pubmed search. Trial characteristics (type, line, regimen), tumor type, and outcomes were analyzed. Line of therapy was categorized as first-line (first line only), early-line (2(nd) and 1-2 line), and any/late-line (2+ lines or not specified). Descriptive statistics, Wilcoxon signed rank, and univariate linear regression were performed. RESULTS: 226 Phase II trials were abstracted. 31% were first-line, 30% early-line, and 39% any/late-line. 83% (187) were single-arm design; 12% (27) and 5% (11) were randomized and cohort studies, respectively. Overall response rate (ORR) was reported in 204 (90%) MBP2, stable disease (SD) in 127 (56%), time to progression (TTP) in 185 (82%), progression free survival in 20 (9%), and overall survival (OS) in 143 (63%). SD was defined as 6 months in 29%, but definitions varied, and SD was not defined in 43%. Overall, median ORR was 36% (IQR: 16-52, range 0-98%); TTP was 27 weeks (IQR: 15-36, range 4-122), and OS was 65 weeks (IQR: 52-95). For first-line, median ORR, TTP, and OS were 53%, 35 weeks, and 97 weeks, respectively. In first-line, ORR ranged from 5%-98%, TTP from 9-72 weeks, and OS from 13-884 weeks. For early-line vs. any/late line, median ORR was 30% vs. 22%, median TTP was 24 vs. 19 weeks, and median OS was 60 vs. 56 weeks. ORR, TTP, and OS differed significantly by line of therapy (all p<0.0001). Univariate linear regression demonstrated a significant association between ORR, TTP, and OS (p<0.005). CONCLUSIONS: Appraisal of recent trials can provide benchmarks for evaluation of novel therapy. As with standard interventions, outcomes in MBP2 vary by line of therapy. Standardization in reporting outcomes, particularly definition of SD, would improve assessment and support rational decision making for which interventions should move forward to Phase III trials.
Authors
Kamal, A; Zhang, T; Schneider, A; Patel, K; Hamilton, EP; Marcom, PK; Peppercorn, JM
MLA Citation
Kamal, A., et al. “Outcomes in phase II trials of metastatic breast cancer: Where is the bar?.” J Clin Oncol, vol. 29, no. 15_suppl, May 2011.
URI
https://scholars.duke.edu/individual/pub1162739
PMID
28022234
Source
pubmed
Published In
Journal of Clinical Oncology
Volume
29
Published Date
Start Page
2590