Antimetastatic drugs: laboratory to clinic~
The purpose of adjuvant chemotherapy is the eradication of micrometastases: is there then any sense in antimetastatic drugs per se? It is frequently stated that since most tumours have already disseminated at diagnosis, the role of antimetastatic drugs is likely to be marginal and confined to those rare cases that have not yet metastasized. Such speculation does not accord with clinical reality since the very common basal cell and squamous cell carcinomas of the skin, even though they may invade, do not metastasize. For many other tumours there are subgroups that metastasize only late, and even with aggressive tumours there may be whole spectra of metastatic behaviour. Moreover, next to nothing is known about the cell traffic between macro and micro-metastases or between the latter and tertiary metastases.
More to the point, however, it has also been said that a really selective anticancer drug will deal with metastases just as effectively as with the primary, if not better. While this may be correct in theory, confidence in the likelihood of discovering such a drug has not been strengthened by the fact that despite intensive research amongst a vast number of substances over the last 35 years, no compound has emerged with the degree of general antitumour selectivity that would have made it instantly recognizable as an 'anticancer penicillin'.
Nor has confidence in the discovery of an 'anticancer penicillin' been helped by the recent recognition in well publicized reports of tumour cell 'heterogeneity', a fact long known to pathologists, but which, in terms of anticancer chemotherapy, means that it is inherently unlikely that some highly specific and selective anticancer agent, that will eradicate all turnour cells, remains to be discovered.
It is clearly a very difficult problem for many reasons and one wishes to minimize neither this Herculean task, nor the efforts of the giants of cancer chemotherapy who have laboured so long and so hard to find just such a drug, prominent amongst whom is the recipient of the honour of this Symposium today--Abe Goldin. He may not be the tallest giant, but he is one of the friendliest and kindest and he has made many notable contributions to the problems of the Experimental Basis of Adjuvant Chemotherapy. One important one (made together with the President of the Congress, Karl Karrer, and the late Stuart Humphreys) was the introduction of the Lewis lung carcinoma (3LL) as a model for metastases [6]. It was only after this acute observation that a search could begin for antimetastatic drugs. Previously, all work on so-called experimental metastasis had to be done by means of i.v. injected tumour cells and the results with this technique, then as now, were largely uninterpretable when correlated with clinical problems.
Achieving turnout control by means of antimetastatic drugs is perhaps therefore, a more achievable goal than eradication of 'cancer' by means of a universal 'anticancer penicillin', chiefly because the mechanism of metastasis formation may The substance of this paper was given at a symposium on Experimental Basis of Adjuvant Chemotherapy at the 13th International Chemotherapy Congress, Vienna on