About

Donald Patrick McDonnell is the Glaxo-Wellcome Distinguished Professor of Molecular Cancer Biology in the School of Medicine at Duke University. He holds multiple positions including Professor of Pharmacology and Cancer Biology, Professor in Medicine, and Professor of Cell Biology. He is also a member of the Duke Cancer Institute. His work is focused on molecular cancer biology, contributing to the understanding of cancer mechanisms and potential therapeutic approaches. As a primary faculty member at Duke, he is actively involved in research and education within the university's biomedical community.

Research topics

• Cancer research
• Genetics
• Endocrinology
• Biology
• Biochemistry
• Chemistry
• Cell biology
• Medicine
• Immunology
• Internal medicine

Selected publications

• Supplementary Fig. 7 from Targeting the ERα DBD–LBD Interface with Mitoxantrone Disrupts Receptor Function through Proteasomal Degradation

  2026-01-02

  articleOpen access

  <p>Supplementary Fig. 7: Comparative transcriptional pathway analysis of MTO and fulvestrant treatments</p>

  PublisherDOI

• Supplementary Fig. 6 from Targeting the ERα DBD–LBD Interface with Mitoxantrone Disrupts Receptor Function through Proteasomal Degradation

  2026-01-02

  articleOpen access

  <p>Supplementary Fig. 6: Comparative pathway analysis reveals distinct transcriptional effects of MTO and fulvestrant</p>

  PublisherDOI

• Supplementary Fig. 4 from Targeting the ERα DBD–LBD Interface with Mitoxantrone Disrupts Receptor Function through Proteasomal Degradation

  2026-01-02

  articleOpen access

  <p>Supplementary Fig. 4: Evaluation of combination treatment effects between MTO and established ER antagonists in MCF7 cells</p>

  PublisherDOI

• Supplementary Fig. 5 from Targeting the ERα DBD–LBD Interface with Mitoxantrone Disrupts Receptor Function through Proteasomal Degradation

  2026-01-02

  articleOpen access

  <p>Supplementary Fig. 5: ER protein levels in wild-type and Y537S ER orthotopic xenograft tumors</p>

  PublisherDOI

• Supplementary Fig. 2 from Targeting the ERα DBD–LBD Interface with Mitoxantrone Disrupts Receptor Function through Proteasomal Degradation

  2026-01-02

  articleOpen access

  <p>Supplementary Fig. 2: MTO demonstrates enhanced growth inhibition in endocrine-resistant T47D cells</p>

  PublisherDOI

• Data from Discovery of BMS-986365, a First-in-Class Dual Androgen Receptor Ligand-Directed Degrader and Antagonist, for the Treatment of Advanced Prostate Cancer

  2026-01-06

  articleOpen access

  <div>AbstractPurpose:<p>BMS-986365, a heterobifunctional androgen receptor (AR) ligand-directed degrader, was designed as a potent cereblon-dependent degrader and competitive antagonist of the AR to overcome resistance to AR pathway inhibition (ARPI) in metastatic prostate cancer.</p>Experimental Design:<p>The <i>in vitro</i> impact of BMS-986365–induced AR degradation on AR activity and prostate cancer cell proliferation was evaluated. Intrinsic agonistic and antagonist activities of BMS-986365 were assessed. The <i>in vivo</i> antitumor activity of BMS-986365 was compared with enzalutamide in multiple cell line– or patient-derived prostate cancer models.</p>Results:<p>BMS-986365 is a potent, rapid, and selective degrader of AR wild-type (WT) and most of the clinically relevant mutants. Degradation of both WT and mutant AR is the key driver of BMS-986365 efficacy, with additional antagonism of residual AR activity enabled through occupancy of its ligand-binding domain. Compared with enzalutamide, BMS-986365 more efficiently inhibits AR target gene transcription and AR-dependent proliferation of prostate cancer cell lines. Whereas enzalutamide increased AR protein in metastatic castration-resistant prostate cancer (CRPC) models, BMS-986365 maintained low levels of AR protein despite increased <i>AR</i> transcript levels. <i>In vivo,</i> BMS-986365 demonstrated on-target activity, degrading AR, suppressing AR signaling, and inhibiting growth in validated cell line– and patient-derived xenograft models of castration-sensitive prostate cancer and advanced and/or therapy-resistant CRPC. Clinically, BMS-986365 reduced PSA in patients with metastatic CRPC after ARPI, including patients with WT AR.</p>Conclusions:<p>The preclinical observations, coupled with clinical data, strongly support the potential for BMS-986365 to overcome ARPI-resistant disease regardless of <i>AR</i> mutational status. These findings establish BMS-986365 as a first-in-class dual AR degrader and competitive antagonist, likely to emerge as an important tool in the armamentarium to treat prostate cancer.</p><p><a href="https://aacrjournals.org/clincancerres/article-abstract/doi/10.1158/1078-0432.CCR-25-3045" target="_blank"><i>See related commentary by Nyquist and Nelson, p. 13</i></a></p></div>

  PublisherDOI

• Supplementary Fig. 1 from Targeting the ERα DBD–LBD Interface with Mitoxantrone Disrupts Receptor Function through Proteasomal Degradation

  2026-01-02

  articleOpen access

  <p>Supplementary Fig. 1: MTO, unlike fulvestrant, maintains E2-mediated ER-SRC3 interaction</p>

  PublisherDOI

• Supplementary Table 1 from Targeting the ERα DBD–LBD Interface with Mitoxantrone Disrupts Receptor Function through Proteasomal Degradation

  2026-01-02

  articleOpen access

  <p>Supplementary Table 1: Analysis of top computational docking candidates from the NIH Clinical Collection</p>

  PublisherDOI

• Supplementary Fig. 3 from Targeting the ERα DBD–LBD Interface with Mitoxantrone Disrupts Receptor Function through Proteasomal Degradation

  2026-01-02

  articleOpen access

  <p>Supplementary Fig. 3: Three-dimensional spheroid growth in MCF7 cells expressing wildtype and mutant ER</p>

  PublisherDOI

• Supplemental Figure 3 from Clinical Efficacy and Whole-Exome Sequencing of Liquid Biopsies in a Phase IB/II Study of Bazedoxifene and Palbociclib in Advanced Hormone Receptor–Positive Breast Cancer

  2025-11-25

  articleOpen access

  <p>Supplemental Figure 3: Plasma circulating tumor DNA (ctDNA) tumor fraction (TF) dynamics determined with ULP-WGS</p>

  PublisherOA PDFDOI

Recent grants

• The role of ERRalpha/PGC-1 in disease pathogenesis

  NIH · $1.6M · 2006–2018

• NIH Grant R01HD058640

  NIH · $817k · 2011

• NIH Grant R01DK050494

  NIH · $2.5M · 2005

• NIH Grant R01CA139818

  NIH · $1.7M · 2013

• NIH Grant R01CA090645

  NIH · $1.9M · 2006

Frequent coauthors

• John D. Norris

  198 shared

• Ching‐yi Chang

  Duke University

  190 shared

• Rachid Safi

  Duke University

  105 shared

• Erik R. Nelson

  University of Illinois Urbana-Champaign

  102 shared

• Suzanne E. Wardell

  Duke University

  100 shared

• Bryan M. Wittmann

  78 shared

• Dmitri Kazmin

  Stanford University

  78 shared

• Mary A. Dwyer

  National Comprehensive Cancer Network

  69 shared

Labs

• McDonnell LabPI

  Our Team Binita Chakraborty, PhD Research Scientist Marina Alorda Clara, PhD Postdoctoral Fellow Jillian Caiazzi Graduate Student Ching-yi Chang, PhD ...

Awards & honors

• Glaxo-Wellcome Distinguished Professor of Molecular Cancer B…