50 Chemotherapy
anticancer agents
Chemotherapy for cancer can be used in isolation or as an adjunct to other forms of therapy. Compared with bacterial disease, cancer presents a difficult problem in that cancer cells and normal cells are similar in many respects. Consequently, it is more difficult to find general, exploitable, biochemical differences between them. Cancer cells differ from normal cells in four ways:
The drugs used in cancer therapy target the cellular mechanisms of uncontrolled proliferation and many target the ability of cells to divide (Fig. 3.50.1). Most anticancer drugs will also affect rapidly dividing normal cells and so are likely to have unwanted effects of depression of bone marrow and growth, impairment of healing, hair loss, sterility and teratogenicity. Many cause nausea and vomiting.
Alkylating agents
One of the major classes of drug used in the treatment of cancer are agents that directly alkylate DNA, including nitrogen mustards (cyclophosphamide, ifosfamide), nitrosoureas (lomustine, carmustine) and others (cisplatin, busulphan, dacarbazine), thereby impairing DNA synthesis and cell division (Fig. 3.50.1). Some require enzymatic conversion (e.g. cyclosphosphamide, ifosfamide and dacarbazine) or spontaneous conversion (e.g. lomustine) to an active alkylating metabolite. They have a preferential activity on rapidly proliferating cells and are not cell cycle specific. However, as the cell enters S phase, the presence of damaged DNA (in this case alkylated) signals cell cycle arrest and cell death. Side-effects of cytotoxic drugs include myelosuppression, alopecia, inhibited proliferation of gastrointestinal epithelium and fertility effects.
