Anette U. Duensing, MD
Associate Professor of Pathology

Dr. Duensing is a member of the Cancer Therapeutics Program at the University of Pittsburgh Cancer Institute.

Office Location:
University of Pittsburgh Cancer Institute
Hillman Cancer Center Research Pavilion, Suite G.17
5117 Centre Avenue
Pittsburgh, PA 15232
Contact Information:
Office Telephone: 412-623-5870
Lab Phone: 412-623-7731
Fax: 412-623-1010
Administrative Support: Ms. Brenda Atoo


  • MD - University of Hannover Medical School, Hannover, Germany, 1997


  • Medical Board of Lower Saxony, Germany

Research Interests

Gastrointestinal stromal tumors (GISTs) are caused by oncogenic mutations in the KIT or PDGFRA protein kinases. They are the prototypical example of a solid tumor entity that can now be successfully treated with a novel class of drugs, tyrosine kinase inhibitors (TKIs). Imatinib mesylate (Gleevec®) is the first and most prominent inhibitor belonging to this group. Although imatinib has revolutionized the treatment of GIST, the occurrence of imatinib-resistant tumors is a problem for a large number of patients. It is therefore imperative to find novel treatment options for these patients. Only two other FDA-approved therapy options exist to date (sunitinib, Sutent®, regorafenib, Stivarga®). Both compounds also target the activated KIT/PDGFRA kinases. However, the most prominent TKI-resistance mechanisms involve secondary mutations in KIT/PDGFRA genes making a "kinase-centric" approach difficult. Our laboratory therefore uses a different approach to identify novel treatments. We are focusing on two major strategies.

Our first line of research uses a candidate approach to find new targets. Here, we are aiming to dissect the molecular mechanisms of action of imatinib. Imatinib rapidly abolishes aberrant KIT and PDGFRA signaling activity, but the precise molecular events that lead to GIST cell eradication are not well understood. Moreover, it is known from clinical observations as well as our previous work that imatinib can also directly induce a state of tumor dormancy (quiescence) leading to residual tumor mass that resumes growth should imatinib therapy be discontinued. Our goal is to identify the molecular players that are involved in imatinib-induced apoptosis and quiescence. In a second step we will use our knowledge to target these molecules for therapeutic purposes.

Our second major line of research employs medium- to large-scale screening strategies. We are currently using siRNA-based screens to identify survival kinase other than KIT/PDGFRA that could be targeted for therapy in GIST. In a second screening approach, we are utilizing compound libraries focusing on compounds that are already FDA-approved to be able to rapidly move them into the clinic.

Our ultimate goal is to generate a framework for future translational studies to improve the therapeutic options for GIST patients. With this framework we hope to be able to develop innovative strategies to treat GISTs more effectively, to achieve more long-term remissions and eventually to overcome Gleevec® resistance.


Medical Board of Lower Saxony, Germany

Honors and Awards

  • Fellow of the Dr. Mildred Scheel Stiftung für Krebsforschung, 1999-2000
  • Scholar-in-Training Award, American Association for Cancer Research (AACR - AstraZeneca), 2003
  • Member, Medical Advisory Board, GIST Cancer Research Fund, 2006-present
  • Member, GIST Collaborative Research Team, The Life Raft Group, 2008-present
  • Member, NIH Pediatric and wildtype GIST Clinic, Consortium for Pediatric and wildtype GIST Research (CPGR), 2010-present
  • Hillman Fellow for Innovative Cancer Research, 2010
  • UPCI Junior Scholar Award in Basic Cancer Research, 2010
  • Speaker, Laureate Society Dinner, American Cancer Society, 2011
  • Member, AACR Stand Up to Cancer (SU2C) - Farrah Fawcett Foundation Human Papillomavirus Translational Research Team Grant Joint Scientific Advisory Committee (JSAC), 2013-2014
  • Jeroen Pit Science Award, The Life Raft Group, 2014
  • GIST Science Award, GIST Patient Group Switzerland, 2014
  • Discussant, Poster Discussion Session "Sarcoma", ASCO Annual Meeting, Chicago, IL, 2015

Selected Publications

View Dr. Duensing's publications on PubMed

  • Heinrich MC, Corless CL, Duensing A, McGreevey L, Chen CJ, Joseph N, Singer S, Griffith DJ, Haley A, Town A, Demetri GD, Fletcher CDM, Fletcher JA. PDGFRA activating mutations in gastrointestinal stromal tumors. Science 2003; 299:708-710.
  • Liu Y, Tseng M, Perdreau SA, Rossi F, Antonescu C, Besmer P, Fletcher JA, Duensing S, Duensing A. Histone H2AX is a mediator of gastrointestinal stromal tumor (GIST) cell apoptosis following treatment with imatinib mesylate. Cancer Res. 2007; 67:2685-2692.
  • Boichuk S, Parry JA, Makielski KR, Litovchick L, Baron JL, Zewe JP, Wozniak A, Mehalek KR, Korzeniewski N, Seneviratne DS, Schöffski P, Debiec-Rychter M, DeCaprio JA, Duensing A. The DREAM complex mediates GIST cell quiescence and is a novel therapeutic target to enhance imatinib-induced apoptosis. Cancer Res. 2013; 73:5120-5129.
  • Boichuk S, Lee DJ, Mehalek KR, Makielski KR, Wozniak A, Seneviratne DS, Korzeniewski N, Cuevas R, Parry JA, Zewe JP, Brown MF, Taguchi T, Schöffski P, Debiec-Rychter M, Duensing A. Unbiased compound screening identifies unexpected drug activities and novel treatment options for gastrointestinal stromal tumors (GIST). Cancer Res. 2014; 74:1200-1213.
  • Höfflin R, Lahrmann B, Warsow G, Hübschmann D, Spath C, Walter B, Hofer L, Macher-Goeppinger S, Tolstov Y, Korzeniewski N, Duensing A, Grüllich C, Jäger D, Perner S, Schönberg G, Nyarangi-Dix J, Isaac S, Hatiboglu G, Teber D, Hadaschik B, Pahernik S, Roth W, Eils R, Schlesner M, Sültmann H, Hohenfellner M, Grabe N, Duensing S. Quantitative image analysis and regional whole exome sequencing indicate spatial niche formation, but not malignant progression, as driving force for intratumoral heterogeneity. Nature Commun. 2016; 7:11845.
  • Rausch JL, Boichuk S, Ali AA, Patil SS, Liu L, Lee DM, Brown MF, Makielski KR, Liu Y, Taguchi T, Kuan SF, Duensing A. Opposing roles of KIT and ABL1 in the therapeutic response of gastrointestinal stromal tumor (GIST) cells to imatinib mesylate. Oncotarget 2017; 8:4471-4483.
  • Dorchak JA, Sifat M, Guarinoni JL, Duensing A, Somiari S, Cavanaugh J, Deyarmin B, Hu H, Iida J, Shriver CD, Witt-Enderby PA. The impact of hormonal contraception on breast cancer pathology. Horm. Cancer 2018; April 23, 2018 (epub ahead of print).
  • Lee DM, Duensing A. What's the FOX got to do with the KITten? Regulating the lineage-specific transcriptional landscape in GIST. Cancer Discovery 2018; 8:146-149.
  • Heinrich MC, Patterson J, Beadling C, Wang Y, Debiec-Rychter M, Dewaele B, Corless CL, Duensing A, Raut C, Rubin BP, Ordog T, van de Rijn M, Call J, Mühlenberg T, Fletcher JA, Bauer S. Genomic aberrations in cell cycle genes predict progression of KIT-mutant gastrointestinal stromal tumors (GISTs). Clin. Sarcoma Res. 2019; 9:3.
  • Rausch JL, Ali AA, Lee DM, Gebreyohannes YK, Mehalek KR, Agha A, Patil SS, Tolstov Y, Wellens J, Dhillon HS, Makielski KR, Debiec-Rychter M, Schöffski P, Wozniak A, Duensing A. Differential antitumor activity of compounds targeting the ubiquitin-proteasome machinery in gastrointestinal stromal tumor (GIST) cells. bioRxiv. doi: 10.1101/791426. Sci. Rep. 2020.