this drug was pivotal in the cure of testicular cancer. subsequently, eve wiltshaw and others at the institute of cancer research in the united kingdom extended the clinical usefulness of the platinum compounds with their development of carboplatin, a cisplatin derivative with broad antitumour activity and comparatively less nephrotoxicity. nitrosoureas a second group with an nci contract, led by john montgomery at the southern research institute, synthesized nitrosoureas, an alkylating agent which cross-links dna. fludarabine phosphate, a purine analogue which has become a mainstay in treatment of patients with chronic lymphocytic leukaemia, was another similar development by montgomery. anthracyclines and epipodophyllotoxins other effective molecules also came from industry during the period of 1970 to 1990, including anthracyclines and epipodophyllotoxins — both of which inhibited the action of topoisomerase ii, an enzyme crucial for dna synthesis. supportive care during chemotherapy as is obvious from their origins, the above cancer chemotherapies are essentially poisons. patients receiving these agents experienced severe side-effects that limited the doses which could be administered, and hence limited the beneficial effects. clinical investigators realized that the ability to manage these toxicities was crucial to the success of cancer chemotherapy. several examples are noteworthy. many chemotherapeutic agents cause profound suppression of the bone marrow. this is reversible, but takes time to recover. support with platelet and red-cell transfusions as well as broad-spectrum antibiotics in case of infection during this period is crucial to allow the patient to recover. several practical factors are also worth mentioning. most of these agents caused very severe nausea (termed chemotherapy-induced nausea and vomiting (cinv) in the literature) which, while not directly causing patient deaths, was unbearable at higher doses. the development of new drugs to prevent nausea (the prototype of which was ondansetron) was of great practical use, as was the design of indwelling intravenous catheters (e.g. hickman lines and picc lines) which allowed safe administration of chemotherapy as well as supportive therapy. bone marrow transplantation one important contribution during this period was the discovery of a means that allowed the administration of previously lethal doses of chemotherapy. the patient's bone marrow was first harvested, the chemotherapy administered, and the harvested marrow then returned to patient a few days later. this approach, termed autologous bone marrow transplantation, was initially thought to be of benefit to a wide group of patients, including those with advanced breast cancer. however, rigorous studies have failed to confirm this benefit, and autologous transplantation is no longer widely used for solid tumors. the proven curative benefits of high doses of chemotherapy afforded by autologous bone marrow rescue are limited to both hodgkin's and selected non-hodgkin's lymphoma patients who have failed therapy with conventional combination chemotherapy. autologous transplantation continues to be used as a component of therapy for a number of other hematologic malignancies. antihormone therapy the hormonal contribution to several categories of breast cancer subtypes was recognized during this time, leading to the development of pharmacological modulators (e.g. of oestrogen) such as tamoxifen. targeted therapy bcr-abl kinase, which causes cml, inhibited by imatinib (small molecule). molecular genetics has uncovered signalling networks that regulate cellular activities such as proliferation and survival. in a particular cancer, such a network may be radically altered, due to a chance somatic mutation. targeted therapy inhibits the metabolic pathway that underlies that type of cancer's cell division. tyrosine kinase inhibitors further information: bcr-abl tyrosine kinase inhibitors the classic example of targeted development is imatinib mesylate (gleevec), a small molecule which inhibits a signaling molecule kinase. the genetic abnormality causing chronic myelogenous leukemia (cml) has been known for a long time to be a chromosomal translocation creating an abnormal fusion protein, kinase bcr-abl, which signals aberrantly, leading to uncontrolled proliferation of the leukemia cells. imatinib precisely inhibits this kinase. unlike so many other anti-cancer agents, this pharmaceutical was no accident. brian druker, working in oregon health & science university, had extensively researched the abnormal enzyme kinase in cml. he reasoned that precisely inhibiting this kinase with a drug would control the disease and have little effect on normal cells. druker collaborated with novartis chemist nicholas lydon, who developed several candidate inhibitors. from these, imatinib was found to have the most promise in laboratory experiments. first druker and then other groups worldwide demonstrated that when this small molecule is used to treat patients with chronic-phase cml, 90% achieve complete haematological remission. it is hoped that molecular targeting of similar defects in other cancers will have the same effect. monoclonal antibodies another branch in targeted therapy is the increasing use of monoclonal antibodies in cancer therapy. although monoclonal antibodies (immune proteins which can be selected to precisely bind to almost any target) have been around for decades, they were derived from mice and did not function particularly well when administered to humans, causing allergic reactions and being rapidly removed from circulation. "humanization" of these antibodies (genetically transforming them to be as similar to a human antibody as possible) has allowed the creation of a new family of highly effective humanized monoclonal antibodies. trastuzumab, a drug used to treat breast cancer, is a prime example. effectiveness the discovery that certain toxic chemicals administered in combination can cure certain cancers ranks as one of the greatest in modern medicine. childhood all (acute lymphoblastic leukemia), testicular cancer, and hodgkins disease, previously universally fatal, are now generally curable diseases. they have also proved effective in the adjuvant setting, in reducing the risk of recurrence after surgery for high-risk breast cancer, colon cancer, and lung cancer, among others. the overall impact of chemotherapy on cancer survival can be difficult to estimate, since improved cancer screening, prevention (e.g. anti-smoking campaigns), and detection all influence statistics on cancer incidence and mortality. in the united states, overall cancer incidence rates were stable from 1995 through 1999, while cancer death rates decreased steadily from 1993 through 1999. again, this likely reflects the combined impact of improved screening, prevention, and treatment. nonetheless, cancer remains a major cause of illness and death, and conventional cytotoxic chemotherapy has proved unable to cure most cancers after they have metastasized.