Current Issues in Cancer: Cancer chemotherapy: identifying novel anticancer drugsBMJ 1994; 308 doi: https://doi.org/10.1136/bmj.308.6939.1288 (Published 14 May 1994) Cite this as: BMJ 1994;308:1288
- J Carmichael
- CRC Academic Unit of Clinical Oncology, Nottingham City Hospital, Nottingham NG5 1PB.
There are now around 60 cytotoxic drugs licensed for use in cancer therapy in the United Kingdom. For certain malignancies such as childhood cancers, haematological malignancies, and germ cell tumours chemotherapy has been pivotal to the substantial improvement in therapeutic outcome achieved over the past 10 years. In contrast, improvements in the systemic management of adult solid tumours have been less dramatic. There is a clear and urgent need for new, more effective drugs for lung, breast, and colorectal malignancies. This paper examines the processes in identifying, developing, and evaluating new drugs with anticancer activity.
Current cytotoxic drugs
Cytotoxic drugs can broadly be grouped into classes relating to their action at the cellular level (box). Most drugs in current use inhibit cellular proliferation, commonly by inhibiting DNA or RNA synthesis. In contrast, other anticancer agents, including hormone analogues such as tamoxifen, induce growth inhibition through interaction with specific nuclear receptors.
Origin of current cytotoxic drugs
The search for active new anticancer drugs over the past decade has proved difficult, but one approach has been by review of the origin of our current compounds. Certain compounds, such as vincristine, were isolated through large scale drug screening programmes, whereas others were produced via analogue development, as illustrated by the new platinum compounds. In contrast, comparatively few cytotoxic drugs have been specifically designed to attack particular cellular targets, though this type of approach did lead to the development of particular antimetabolites used today, such as aminopterin and methotrexate. Serendipity has undoubtedly played a major part in identifying other important cytotoxic drugs - for instance, cisplatin.
For the past 40 years the National Cancer Institute in the United States has carried out large scale screening of compounds with potential anticancer activity.1 The screen has been used to evaluate a wide range of agents, including natural products and synthetic chemicals developed in …