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HISTORY OF CANCER TREATMENT AND DRUG DESIGN
Discovery of Anti cancer drugs were started in 1940. Most of the agents were discovered in 1950-1970. The era of cancer began first with chemotherapy in the 1940s with the first use of nitrogen mustard's and folic acid antagonist drugs. Cancer drug development has exploded since then into a multimillion dollar industry. The targeted therapy revolution has arrived, but many of the principles and limitations of chemotherapy discovered by the early researchers still apply.
It was, however, four World War II–related programs, and the effects of drugs that evolved from them, that provided the impetus to establish in 1955 the national drug development effort known as the Cancer Chemotherapy National Service Center. The ability of combination chemotherapy to cure acute childhood leukemia and advanced Hodgkin disease in the 1960s and early 1970s overcame the prevailing pessimism about the ability of drugs to cure advanced cancers, facilitated the study of adjuvant chemotherapy, and helped foster the national cancer program. Today, chemotherapy has changed as important molecular abnormalities are being used to screen for potential new drugs as well as for targeted treatments.[15.16]
In the early 1900s, the famous German chemist Paul Ehrlich set about developing drugs to treat infectious diseases. He was the one who coined the term “chemotherapy” and defined it as the use of chemicals to treat disease. He was also the first person to document the effectiveness of animal models to screen a series of chemicals for their potential activity against diseases, an accomplishment that had major ramifications for cancer drug development. In 1908, his use of the rabbit model for syphilis led to the development of arsenicals to treat this disease. Ehrlich was also interested in drugs to treat cancer, including aniline dyes and the first primitive alkylating agents, but apparently was not optimistic about the chance for success.Surgery and radiotherapy dominated the field of cancer therapy into the 1960s until it became clear that cure rates after ever more radical local treatments had plateaued at about 33% due to the presence of heretofore-unappreciated micrometastases and new data showed that combination chemotherapy could cure patients with various advanced cancers. The latter observation opened up the opportunity to apply drugs in conjunction with surgery and/or radiation treatments to deal with the issue of micrometastases, initially in breast cancer patients, and the field of adjuvant chemotherapy was born. Combined modality treatment, the tailoring of each of the three modalities so their antitumor effect could be maximized with minimal toxicity to normal tissues, then became standard clinical practice. [15,16]
A selected history and timeline of events related to the development of cancer chemotherapy is shown in figure 1. The first four decades of the 20th century were primarily devoted to model development. The major limitations of drug discovery were two-fold: first, the development of models that could effectively be used to reduce the vast repertoire of chemicals to those few that might have activity against cancer in humans, and second, the access to clinical facilities to test such agents. A major breakthrough in model development occurred in the early 1910s when George Clowes of Roswell Park Memorial Institute (RPMI) in Buffalo, New York, Roswell Park Memorial Institute developed the first transplantable tumor systems in rodents. This advance allowed the standardization of model systems and the testing of larger numbers of chemicals. Significant efforts were subsequently focused on identifying the ideal model system for cancer drug testing, which then became a major thrust of research for the next several decades. The early model systems that were developed included Sarcoma 37 (S37), Sarcoma 180 (S180), Walker 256, and Ehrlich's ascites tumor, all carcinogen-induced tumors in mice.[15.16]