This unique volume traces the critically important pathway by which a molecule becomes an
anticancer agent. The recognition following World War I that the administration of toxic
chemicals such as nitrogen mustards in a controlled manner could shrink malignant tumor masses
for relatively substantial periods of time gave great impetus to the search for molecules that
would be lethal to specific cancer cells. Weare still actively engaged in that search today.
The question is how to discover these anticancer molecules. Anticancer Drug Development Guide:
Preclinical Screening Clinical Trials and Approval Second Edition describes the evolution to
the present of preclinical screening methods. The National Cancer Institute's high-throughput
in vitro disease-specific screen with 60 or more human tumor cell lines is used to search for
molecules with novel mechanisms of action or activity against specific phenotypes. The Human
Tumor Colony-Forming Assay (HTCA) uses fresh tumor biopsies as sources of cells that more
nearly resemble the human disease. There is no doubt that the greatest successes of traditional
chemotherapy have been in the leukemias and lymphomas. Since the earliest widely used in vivo
drug screening models were the murine L 1210 and P388 leukemias the community came to assume
that these murine tumor models were appropriate to the discovery of antileukemia agents but
that other tumor models would be needed to discover drugs active against solid tumors.
