Affiliation: Dep. of Oncology, “MarioNegri” Institute for Pharmacological Research, Milan Italy, Via Eritrea N62, 20154 Milan Italy
The conventional chemotherapy is mostly based on the evidence that proliferating cells are more sensitive to anticancer agents than non-dividing cells. This is the main reason why these compounds are not tumour specific and their selectivity is generally in favour of rapidly growing cells (haematopoietic or intestine. i.e.) rather than discriminating against any fundamental biological difference between normal and tumour cells. The critical issue is at present to identify how tumour cells differ from normal cells and how those differences can be exploited therapeutically for designing and synthesising new drugs with a selective mechanism of action and thus with an improved therapeutic index. This topic and the strategies to identify these new targets will be discussed in details in the review. The expanding knowledge on molecular biology of cancer cells has allowed in the last years the identification of different molecular pathways altered in cancer that could be exploited as potential therapeutic targets. For most of the pathways previously disclosed it has been a problem to develop selective molecules with a relevant clinic impact. To target those specific genetics defects, different kind of molecules (antibodies, “antisense oligonucleotides”, short peptides and small molecules) have been made and some of them are currently under investigation. This review will be focused mainly on three different classes of compounds: I. Compounds designed to hit or inhibit crucial molecular targets. II. Novel DNA minor groove binders. III. Products of marine origin that exhibit novel mode of action.