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Reference EPFL-ARTICLE-204084doi:10.1007/s10549-014-3174-5View record in Web of Science Record created on 2014-12-30, modified on 2017-12-10

N-methylmelamines have been investigated as potential anti-tumour agents for nearly forty years (Fig. 1). The parent compound, hexamethylmelamine (HMM) was first synthesised in 1951 in the search for synthetic resins and fibres (1). It was shown at the time that HMM and N2,N4,N6-trihydroxymethylmelamine were cytotoxic versus the Walker 256 tumour in the rat (2,3). However, HMM was not tested in phase I trials until 1965 in which anti-tumour activity was observed against ovarian and lung cancer (4). Nausea and vomiting were dose limiting, additional toxicities being neuropathy and myelosuppression as confirmed by a subsequent study (5). Phase II studies were carried out in the early 1970’s and demonstrated broad spectrum anti-tumour activity (6,7).

The approach described herewith is an attempt to use antibodies directed towards tumor-associated antigens or other polymers or macromolecules, as carriers for cytotoxic anti-cancer agents in order to improve the effectiveness of cancer chemotherapy.

The possibility of using cyclic AMP either as an inhibitor of cell proliferation, or to facilitate the reversal of the abnormally differentiated state of neoplastic tumours has been considered. The parameters involved in regulation of intracellular levels of cyclic AMP have been defined. The anti-tumour akylating agents have been given as an example of tumour growthinhibitors the mechanism of action of which may involve cyclic AMP.