Anita Turk, M.D.
535 Barnhill Drive
Indianapolis, IN 46202
Phone: (317) 274-0358
Research Program Membership
Dr. Turk's research interests include:
My overarching career goal is to identify and develop novel therapeutic strategies to improve clinical outcomes for patients with cholangiocarcinoma and pancreatic cancers. I hope to progress the field in partnership with a basic scientist to evaluate innovative treatments for our patients. There has been rapid progress in the fields of targeted and immunotherapy in solid tumors. Unfortunately, development in cholangiocarcinoma has remained limited. The ABC-02 trial established benefit of gemcitabine and cisplatin as standard of care for first-line chemotherapy in fit patients. However, all patients ultimately progress after this therapy, and there are no standard second-line options. Though there has been break-through in targeted-therapy for intrahepatic cholangiocarcinoma, a vast majority of patients will not harbor IDH1 mutations or FGFR2 fusions. Hence, there is a clear unmet need to develop novel therapeutic strategies for this patient population. The ubiquitin proteasome system (UPS) controls a broad array of cellular functions via protein degradation. Ubiquitin (Ub) conjugation via covalent linkage to a protein tags it for degradation by a proteasome. Ubiquitylation is a multi-step process that transfers Ub to target substrates through an enzymatic cascade that involves three enzymes: Ub-activation (E1), Ub-conjugating (E2), and Ub-ligase (E3). A subgroup of E3 ligases include Cullin RING ligases (CRL) which are responsible for approximately 20% of cellular proteins labeled for degradation. CRL substrates include regulators of cell cycle progression, apoptosis, DNA damage responses, and signaling transduction. This subgroup of E3 ligases are regulated via a Ub-like ligand, NEDD8, via covalent conjugation via a process called neddylation. Pre-clinical work by Gao et al studied tumor samples from 322 patients with resected intrahepatic cholangiocarcinoma (ICC) and demonstrated that neddylation was upregulated in over two-thirds of cases. To illustrate the clinical relevance of neddylation upregulation, the authors then grouped patients according to high or low expression of these markers. Univariate analyses demonstrated that upregulation of the neddylation pathway correlated with higher rate of relapsed disease after resection. Patients with low expression of NEDD8 had a median time to recurrence of 44.0 months compared to 14.0 months in patients with high expression of NEDD8. Pevonedistat, a neddylation inhibitor, is an agent listed on the NCI Cooperative Research and Development Agreement and is undergoing development in solid tumor and B-cell malignancies. We are developing randomized phase II study evaluating pevonedistat as a single agent and as part of combination therapy with carboplatin and paclitaxel for patients with unresectable cholangiocarcinoma in the second and third-line setting. I developed this concept and with Dr. Dustin Deming and wrote the letter of intent. This trial has been approved by ECOG and CTEP and the protocol is currently under development.
Fellowship - University of Wisconsin, Madison, WI 06/2018
Residency - University of Chicago, Chicago, IL 06/2015
M.D. - Indiana University School of Medicine, Indianapolis, IN 06/2012