Treatment Therapies
Targeted therapies - Overview of cytotoxic drugs
Many new cytotoxic drugs for treating NSCLC were developed in the last quarter of the 20th century. The most effective drugs are those that either directly damage deoxyribonucleic acid (DNA) or disrupt accurate DNA replication and segregation prior to cell division. For example, the platinum compounds cross-link DNA causing damage and preventing replication. Antimetabolites, such as gemcitabine and 5-fluorouracil (5-FU), are chemical analogues of DNA bases. Consequently, these compounds interfere with the synthesis of DNA bases and stop the S-phase of the cell cycle (i.e. DNA replication). The camptothecins interfere with enzymes that unwind DNA during replication and also arrest the cell cycle in the S-phase. Taxanes prevent spindle formation, resulting in the failure of chromosome alignment immediately prior to cell division (i.e. mitosis).
As all of these drugs act on mechanisms central to cell division, they are effective against the rapidly dividing cells characteristic of malignant tumours. However, as a consequence, drugs of this type are also toxic to healthy tissues that have high rates of cell division, e.g. gastrointestinal tract, bone marrow, hair follicles, and male reproductive organs. For many drugs, this indiscriminate targeting of rapidly dividing cells and its associated toxicity limits their clinical usefulness.
Thus, there is a clinical need to develop other anticancer agents more specifically targeted to tumour cells, thereby reducing unwanted side effects on healthy tissues. Such research has been made possible by an increased understanding of cancer cell biology.
