ABSTRACT
Modern cancer chemotherapy originated with the development of chemicals that were used as weapons in World War I. In the 1940s, a team of scientists led by Goodman and Gilman initiated the first cancer chemotherapy trial. While investigating chemical warfare agents, they found that nitrogen mustard, known to induce leukopenia in exposed soldiers, had cytotoxic effects in animals. Believing that these agents could have the same effect on the uncontrolled growth of lymphoid cells, they applied this to a patient in the terminal stages of non-Hodgkin’s lymphoma. The result was a dramatic, although short lived, response (1). Their success and subsequent trials in individual patients heralded the beginning of a new era in cancer treatment. In the same decade, researchers noted that the recently discovered vitamin, folic acid, enhanced cell proliferation in children with acute lymphoblastic leukemia (ALL). Sydney Farber at HarvardMedical School developed methotrexate (MTX), a folic acid antagonist and the first drug to induce remission in a hematologic neoplasm (2). These steps led to a major congressionally funded effort by the National Cancer Institute (NCI) to research and develop chemotherapy (3). Over the next 60 years, thousands of researchers developed scores of new agents for clinical use. Ongoing pharmacological discoveries continue to change the ways in which cancer is treated.
