Anette U. Duensing, MD
Assistant Professor of Pathology
Dr. Duensing is a member of the University of Pittsburgh Cancer Institute.
University of Pittsburgh Cancer Institute
Hillman Cancer Center Research Pavilion, Suite 1.8
5117 Centre Avenue
Pittsburgh, PA 15232
Office Telephone: 412-623-5870
Lab Phone: 412-623-7731
- MD - University of Hannover Medical School, Hannover, Germany, 1997
CertificationMedical Board of Lower Saxony, Germany
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.
CertificationsMedical 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 PublicationsView Dr. Duensing's publications on PubMed
- 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.
- DeCaprio JA, Duensing A. The DREAM complex in anti-tumor activity of imatinib in gastrointestinal stromal tumors. Curr Opin Oncol 2014; 26:415-421.
- Duensing A. Targeting ETV1 in gastrointestinal stromal tumors: Tripping the circuit breaker in GIST? Cancer Discovery 2015, 5:231-233.
- Duensing A. New targets, novel treatments could achieve translational results and enhanced apoptosis of GIST cells. The GIST Cancer Journal 2015; 2:4-9.
- Duensing A. Tracking the Trials and Progress of Drugs in the Pipeline: New Directions in Novel Treatments and Identification of Pathways. The GIST Cancer Journal 2015; 2:34-37.