Lynn M. Matrisian, PhD, MBA
Lynn is Chief Science Officer at the Pancreatic Cancer Action Network, based in Manhattan Beach, CA and Washington DC, USA. She focuses on understanding and impacting the scientific and medical activities within the pancreatic cancer field to advance the organizations goal to double survival from pancreatic cancer by the year 2020. She has oversight of the organization’s research activities, including the Grants Program, Clinical Trial Finder, Patient Registry, Know Your Tumor and Early Detection Initiative, and sits on the Steering Committee of the personalized medicine initiative Precision Promise. Dr. Matrisian is formerly Professor and the founding Chair of the Department of Cancer Biology at Vanderbilt University. She received her PhD in molecular biology from the University of Arizona and MBA from Vanderbilt University. She is past President of the American Association of Cancer Research, a Fellow of the AACR Academy, and the recipient of the Paget-Ewing award from the Metastasis Research Society. She served as co-chair of the National Cancer Institute's Translational Research Working Group and Special Assistant to the Director of the NCI. Research in her laboratory revolved around the molecular mechanisms underlying tumor progression and metastasis, with emphasis on the biology of matrix-degrading proteinases.
The Know Your Tumor® (KYT) initiative was launched in June 2014 to determine if a precision medicine approach is appropriate for pancreatic cancer. Patients are identified through the Pancreatic Cancer Action Network (PanCAN) Patient Central call center and Perthera, Inc obtains patient consent under an IRB approved observational registry study, coordinates molecular testing through external laboratories, convenes a virtual molecular tumor board consisting of medical experts in precision oncology and pancreatic cancer, and prepares a ranked list of therapy options based on the patient’s clinical characteristics, treatment history, and molecular profiling results. Real-world outcomes are collected after delivering a report to the patient’s cancer care team. As of January 2019, more than 1000 individuals have completed KYT from over 300 academic and community practice sites covering 49 states. Tumor samples were adequate for next-generation sequencing in 96% of cases, and KRAS mutations were identified in 92% of those with a PDAC diagnosis. Overall, 27% of patients had highly actionable alterations defined as mutations with a targeted therapy identified as being effective in any cancer type. Patients with a highly actionable alteration who utilized a molecularly matched therapy (n=28) had significantly improved progression-free survival (39.3 vs 10.7 wks, p=.002) compared to those with highly actionable alterations that did not receive matched therapy (n=45). 16.5% of individuals had mutations in homologous recombination repair DNA damage response (HR-DDR) pathway genes (ATM, BRCA1/2, PALB2, SMARCA4, RAD50, BAP1, BRIP1, BARD1, FANCA/C/G, STAG2, CHEK1/2), indicating treatment with platinum-based therapy and/or PARP inhibitors. In a subset analysis, patients with advanced disease and HR-DDR alterations treated with platinum-based therapy had a significantly improved overall survival (2.37 vs 1.45 years, p<.0001, n=54 vs 258 HR-DDR proficient). HR-DDR status had no prognostic significance in platinum-naïve patients. These results suggest that a precision oncology approach to pancreatic cancer is effective and feasible in the US healthcare system.