Precision Cancer Medicine and Investigational Therapeutics (PCMIT)
The PCMIT program organizes and supports Duke Cancer Institute members who are committed to creating better treatment options for patients with cancer and delivering on the promise of precision oncology. The mission of the PCMIT Program is to transform cancer care through the discovery of actionable molecular targets, development of novel therapeutics and diagnostics, and implementation of infrastructure to support translational research and other clinical activities in precision medicine.
- Identification of novel molecular targets in cancers.
- Development of innovative treatments directed at molecular alterations driving proliferation and/or therapy resistance, including strategies to overcome molecular residual disease (MRD).
- Molecular analysis of patient samples including primary tissues, fluids, and patient-derived models of cancer.
- Development and evaluation of novel technologies for molecular analyses.
- Development of new biomarkers for diagnosis, prognosis, and prediction.
- Expansion of precision medicine infrastructure: tumor boards, clinical cancer informatics, and access to biorepository and translational research data.
Shannon McCall, MD. Dr. Shannon McCall is Vice-chair for Translational Research in the Department of Pathology and serves as Director of the Duke BioRepository & Precision Pathology Center. She is also the principal investigator for the Southern Division of the National Cancer Institute (NCI) Cooperative Human Tissue Network (CHTN). She received her B.S. in Chemical Engineering from NC State University and her M.D. from Duke University where she remained for training in Anatomic and Clinical pathology with a fellowship in Gastrointestinal & Hepatic Pathology. She has received funding for her contributions to human sample-based science including improving needle core tumor sampling for cancer research and for providing high-quality, annotated human cancer samples and expert data analysis for the NCI Cancer Genome Atlas (TCGA) project. She earned board certification in Clinical Informatics in 2017 and now develops methods for research biospecimen annotation using clinical pathologic and molecular data. She serves as the Duke Site PI for the American Association for Cancer Research Genomics Evidence Neoplasia Information Exchange (GENIE) project. She is a co-creator of the Molecular Tumor Board process at Duke and serves as PI on Molecular Tumor Board-related research protocols including the umbrella protocol that allows MTB to assist with screening patients for clinical trial enrollment based on their molecular variants.
Dorothy Sipkins, MD, PhD Dr. Sipkins has been an Associate Professor at Duke University in the Dept. of Medicine, Division of Hematologic Malignancies and Cellular Therapy, since 2014. Prior to that, she was an Assistant Professor at the University of Chicago. She received her B.A.S., M.D. and Ph.D. from Stanford University and was a resident and fellow at Massachusetts General Hospital and Dana-Farber Cancer Institute. She currently attends on the inpatient hematologic malignancy service at Duke University Hospital. In her research laboratory, she studies the role of the host bone marrow in regulating the growth and spread of leukemia and breast cancer metastases. Her major focus is in understanding how cancer invasion, proliferation and chemotherapy resistance are regulated by specific molecular interactions with the host tissue (the tumor “microenvironment”). To accomplish this, the Sipkins lab utilizes video-rate, single cell resolution assays including intravital microscopy in order to observe tumor cell interactions with the microenvironment in living mice in real time. Using this approach, her lab has identified molecules and novel pathways that control important steps in bone and brain metastasis. Dr. Sipkins is actively developing early phase clinical trials to test the lab’s pre-clinical findings in patient populations. Dr. Sipkins also serves as a standing member of the NIH Tumor Microenvironment Study Section.
John Strickler, MD. Dr. John Strickler is the Associate Director of Clinical Research – GI Oncology and Co-Leader of the Molecular Tumor Board at the Duke Cancer Institute. He is an Associate Professor of Medicine at Duke University. Dr. Strickler received his B.A. from the University of North Carolina at Chapel Hill and his M.D. from the University of Chicago - Pritzker School of Medicine. He completed his residency in Internal Medicine at the University of Washington and fellowship in Hematology and Medical Oncology at Duke University. Dr. Strickler’s clinic specializes on the treatment of gastrointestinal malignancies, with a particular emphasis on esophageal, gastric, and colorectal cancers. His research focuses on precision cancer medicine: identification of genomic biomarkers that predict sensitivity or resistance to targeted therapies and immunotherapy. He has a particular interest in non-invasive “liquid biopsies” to deliver on the promise of precision cancer medicine. He has designed and executed clinical trials that test novel therapies and innovative therapeutic strategies. He is the principal investigator (PI) on several national multi-site investigator sponsored trials. Nationally, he is co-Chair of the GI Steering Committee for the Academic and Community Cancer Research United (ACCRU) clinical trial consortium.
Centers and Labs
Precision Cancer Medicine Initiative (PCMI): The Duke Precision Cancer Medicine Initiative (PCMI) is comprised of the Duke Molecular Tumor Board (DMTB), the Duke Molecular Registry of Tumors (MrT), and participation in the American Association for Cancer Research (AACR) Genomics Evidence Neoplasia Information Exchange (GENIE) cancer genomic data sharing program, with the goal of promoting precision medicine within the Duke University Health System (DUHS).
BioRepository and Precision Pathology Center: The Duke BRPC has facilitated biospecimen collection and processing for over 10,000 Duke patients participating in clinical trials. In addition, the Duke BRPC has obtained broad consent from over 5,000 patients for blood and leftover cancer tissue donation to research. Through the BRPC, researchers can access over 60,000 dedicated research specimens and millions of leftover clinical pathology samples.
Sipkins Lab: The Sipkins Lab studies the molecular characteristics of tissue microenvironments, or “niches,” that regulate the migration, survival and regeneration of cancerous cells. In combination with classical molecular and cell biology approaches, the lab utilizes state-of-the-art multiphoton and confocal optical imaging techniques to explore these questions in vivo, in real-time in mouse models of leukemia and breast cancer.
KRAS G12C Inhibition with Sotorasib in Advanced Solid Tumors
- Hong DS, Fakih MG, Strickler JH, Desai J, Durm GA, Shapiro GI, Falchook GS, Price TJ, Sacher A, Denlinger CS, Bang YJ, Dy GK, Krauss JC, Kuboki Y, Kuo JC, Coveler AL, Park K, Kim TW, Barlesi F, Munster PN, Ramalingam SS, Burns TF, Meric-Bernstam F, Henary H, Ngang J, Ngarmchamnanrith G, Kim J, Houk BE, Canon J, Lipford JR, Friberg G, Lito P, Govindan R, Li BT. KRASG12C Inhibition with Sotorasib in Advanced Solid Tumors. N Engl J Med. 2020 Sep 24;383(13):1207-1217. doi: 10.1056/NEJMoa1917239. Epub 2020 Sep 20. PMID: 32955176; PMCID: PMC7571518.
A Precision Medicine Drug Discovery Pipeline Identifies Combined CDK2 and 9 Inhibition as a Novel Therapeutic Strategy in Colorectal Cancer:
- Somarelli JA, Roghani RS, Moghaddam AS, Thomas BC, Rupprecht G, Ware KE, Altunel E, Mantyh JB, Kim SY, McCall SJ, Shen X, Mantyh CR, Hsu DS. A Precision Medicine Drug Discovery Pipeline Identifies Combined CDK2 and 9 Inhibition as a Novel Therapeutic Strategy in Colorectal Cancer. Mol Cancer Ther. 2020 Dec;19(12):2516-2527. doi: 10.1158/1535-7163.MCT-20-0454. Epub 2020 Nov 6. PMID: 33158998; PMCID: PMC7718319.
RNA splicing and aggregate gene expression differences in lung squamous cell carcinoma between patients of West African and European ancestry
- Deveaux AE, Allen TA, Al Abo M, Qin X, Zhang D, Patierno BM, Gu L, Gray JE, Pecot CV, Dressman HK, McCall SJ, Kittles RA, Hyslop T, Owzar K, Crawford J, Patierno SR, Clarke JM, Freedman JA. RNA splicing and aggregate gene expression differences in lung squamous cell carcinoma between patients of West African and European ancestry. Lung Cancer. 2021 Mar;153:90-98. doi: 10.1016/j.lungcan.2021.01.015. Epub 2021 Jan 14. PMID: 33465699.
Prior tonsillectomy is associated with an increased risk of esophageal adenocarcinoma
- Garman KS, Ajayi TA, Boutte HJ Jr, Chiu ST, von Furstenberg RJ, Lloyd BR, Zhang C, Onaitis MW, Chow SC, McCall SJ. Prior tonsillectomy is associated with an increased risk of esophageal adenocarcinoma. PLoS One. 2020 Jul 22;15(7):e0235906. doi: 10.1371/journal.pone.0235906. PMID: 32697782; PMCID: PMC7375530.
Characterization of tumor mutation burden, PD-L1 and DNA repair genes to assess relationship to immune checkpoint inhibitors response in metastatic renal cell carcinoma
- Labriola MK, Zhu J, Gupta RT, McCall S, Jackson J, Kong EF, White JR, Cerqueira G, Gerding K, Simmons JK, George D, Zhang T. Characterization of tumor mutation burden, PD-L1 and DNA repair genes to assess relationship to immune checkpoint inhibitors response in metastatic renal cell carcinoma. J Immunother Cancer. 2020 Mar;8(1):e000319. doi: 10.1136/jitc-2019-000319. Erratum in: J Immunother Cancer. 2020 May;8(1): PMID: 32221016; PMCID: PMC7206964.
Targeting cellular heterogeneity with CXCR2 blockade for the treatment of therapy-resistant prostate cancer
- Li Y, He Y, Butler W, Xu L, Chang Y, Lei K, Zhang H, Zhou Y, Gao AC, Zhang Q, Taylor DG, Cheng D, Farber-Katz S, Karam R, Landrith T, Li B, Wu S, Hsuan V, Yang Q, Hu H, Chen X, Flowers M, McCall SJ, Lee JK, Smith BA, Park JW, Goldstein AS, Witte ON, Wang Q, Rettig MB, Armstrong AJ, Cheng Q, Huang J. Targeting cellular heterogeneity with CXCR2 blockade for the treatment of therapy-resistant prostate cancer. Sci Transl Med. 2019 Dec 4;11(521):eaax0428. doi: 10.1126/scitranslmed.aax0428. PMID: 31801883; PMCID: PMC7238624.
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