L6.2 Biopsy-Driven Trials to Identify Biomarkers of Therapeutic Resistance: Biospecimen Collection and Processing to Enable Multi-Dimensional Analysis

Abstract

Personalized medicine is a concept that has raised high expectations amongst scientists, clinicians, and patients. Despite significant advances, therapeutic resistance remains a critical problem, and many multi-dimensional approaches have been used to identify predictive biomarkers and to gather insight into the biology of disease using patient tumor tissue material. However, duplication of results by other groups is often hampered by tumor heterogeneity and pre-analytical variables. Our focus is on the design of prospective clinical trials to identify biomarkers of clinical resistance to therapy using metastatic biopsies from patients before treatment and at the occurrence of resistance. We identified and addressed several critical issues pertaining to pre-analytical biospecimen collection and processing during the course of three biomarker-driven translational research projects in colorectal cancer (Q-CROC-01, NCT00984048), lymphoma (Q-CROC-02, NCT01238692) and triple-negative breast cancer (Q-CROC-03, NCT01276899). We report that histological control of percent tumor cells in each needle core biopsy is absolutely necessary to ensure optimal representation of tumor, and have developed tissue specific methods to both preserve tissue morphology and extract sufficient quality and quantity of RNA and DNA to permit downstream multi-dimensional analysis.