Patient Derived Primary Cells in High Throughput Differential Antitumor Screens Let the Patients Be the Guide

8.1 Introduction

Paul Ehrlich's pioneering work in 1905, which culminated in the discovery of arsephenamine (also known as compound 606 or Salvarsan) for the treatment of syphilis,1 launched the modern concept of using drug discovery screens to identify chemothera-peutics. This approach of screening hundreds, and later thousands, of compounds in a "bioassay" was subsequently applied to the discovery of antitumor drugs. Between 1947 and 1955, Cornelius Packard "Dusty" Rhoads and his team at Sloan-Kettering Institute (New York, NY, U.S.A.) screened an estimated 20,000 compounds (both synthetic and natural) in a sarcoma-180 mouse tumor model.2 Around the same period, Murray Shear and his colleagues at the U.S. National Cancer Institute (NCI, Bethesda, MD, U.S.A.) tested 3000 chemicals and plant materials for potential antitumor activity.3 Later, Abbott, Hartwell, and others at the NCI screened a wide range of natural products in both in vitro and in vivo antitumor bioassays.4

As early as the 1950s, the value of employing primary cells derived from patients' tumors in an antitumor drug discovery screen was recognized.5 The use of patient-derived diseased tissue proved impractical at that time, however, because of the inability to maintain some of the cells in culture and because of insufficient tumor tissue available from patients undergoing surgery. In the 1980s, researchers at the NCI attempted to use patient-derived diseased tissue in a high-throughput screening (HTS) format using a variation of the Hamburger and Salmon clonogenic chemosensitivity assay.6 The authors reported that

Irwin A. Braude

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