Surveillance and Liquid Biopsy: What do you need to know Erica L. Carpenter, MBA, PhD Director, Liquid Biopsy Laboratory Division of Hematology-Oncology University of Pennsylvania School of Medicine May, 2018 Surveillance and liquid biopsy: what do you need to know? What is a liquid biopsy and why should I care? How are liquid biopsies being used in clinical care? What’s the latest in liquid biopsy research? What does the future hold for liquid biopsy? Standard of care tumor surveillance Blood tests Biopsy Imaging Liquid biopsy detects tumor materials shed into the blood https://www.cancer.gov/types/skin/patient/melanoma-treatment-pdq How can a liquid biopsy help? Metastatic site may be difficult or impossible to surgically access Sampling a piece of the tumor can be sub-optimal when tumor is heterogeneous Imaging may not be sufficiently sensitive to detect smaller tumors https://www.cancer.gov/types/skin/patient/melanoma-treatment-pdq Liquid Biopsy Tumor Surveillance - Improving Care While Decreasing Discomfort More of this… …and less of this …or this Adapted from Haber DA and Velculescu VE, Can Disc 2014 What are the different types of liquid biopsy? Circulating Tumor DNA CTCs Adapted from Haber DA and Velculescu VE, Can Disc 2014 What are the different types of liquid biopsy? Exosomes and microvesicles Circulating Tumor DNA Ko J, Carpenter EL, and Issadore DA, RSocChem 2015 CTCs Adapted from Haber DA and Velculescu VE, Can Disc 2014 What are the different types of liquid biopsy? Exosomes and microvesicles Ko J, Carpenter EL, and Issadore DA, RSocChem 2015 Circulating Tumor DNA CTCs Soluble Reprogramming of human cancer cells Factors to pluripotency for models of cancer progression Kim J and Zaret KS EMBO Press 201X Adapted from Haber DA and Velculescu VE, Can Disc 2014 Kim J et al. STM 2017 A liquid biopsy can be more than a blood test More of this… …and less of this ctDNA CTCs Adapted from Haber DA and Velculescu VE, Can Disc 2014 LIQUID BIOPSY Multi-Factorial Matched Tumor Tissue Proteins • Blood • Pleural effusion Exosomes • Marrow aspirate Clinical Sequencing • Cyst fluid ctDNA and Histology • Urine CTCs CTCs to monitor early response to immune therapy Melanoma patients Hong X et al. PNAS 2017 In the era of precision mutation targeting, repeat genetic tumor testing has become essential Tissue Tissue Tissue Tissue Biopsy Biopsy Biopsy Biopsy Months http://www.scienceagogo.com/news/20150211195357.shtml Chapman PB et al. NEJM 2013 Shaw AT et al. NEJM 2016 Pilot lung cancer study: Identifying targetable mutations Enrolled 102 advanced lung cancer patients 31% of patients with a “targetable mutation” Repeat liquid biopsy feasible Managing care in the absence of tissue biopsy 50 Enrolled an additional 324 advanced lung 25 cancer patients 0 Patients not on therapy at the time of -25 liquid biopsy -50 86% response rate -75 % Change in Target Lesion Target %in Change -100 Manuscript in preparation What about for melanoma patients… on therapy? A B Gangadhar T et al., PCMR 2017 Exosomes for detection of early stage cancer Ko J, Carpenter EL, and Issadore DA, RSocChem 2015 Ko J et al. Can Res in press What’s next? Improving cancer survival through liquid biopsy- based early detection, and eventually, screening ctDNA Soluble factors Adapted from Mitch Schnall Tissue single Exosomes CTCs cell analysis.