Anti-Cancer Agents in Medicinal Chemistry (Formerly Current Medicinal Chemistry - Anti-Cancer Agents) - Volume 9, Issue 6, 2009

The use of compounds to affect the activity of proteins (both enzymes and receptors) is still under extensive consideration in the development of novel anti-tumour agents. In this issue, we consider a number of targets which have been (and continue to be) under investigation and which have shown therapeutic/clinical potential in the treatment of cancers. However, due to the nature of the area, it is difficult to undertake an ex Read More

A high proportion (∼40%) of breast cancers are hormone-dependent and it is the female hormone estradiol (E2) that is believed to play a key role in the initiation, promotion and progression of this disease. In the fight against this disease, compounds which are potent inhibitors of the cytochrome P-450 enzyme aromatase (AR) (which catalyses the conversion of the C19 androgens to the C18 estrogens) have been the Read More

Prostate cancer is an age-related disease and a major cause of death in Western countries. A large proportion of prostate cancers have been found to be dependent on androgens for growth and various therapeutic approaches have aimed at either decreasing androgen levels or blocking their action. One method of decreasing androgen levels is through inhibition of enzymes involved in the biosynthetic pathway, for example, th Read More

The genetic control, mechanism of action and inhibition of aromatase for potential therapeutic benefits in the arena of hormone dependent illness continues to be of considerable interest. The work presented here concentrates on recent advances in the mechanistic aspects of the aromatase enzyme and the nature of the chemical entities that lead to its inhibition.

The 17β-hydroxysteroid dehydrogenases (17β-HSDs) are involved in the regulation of estrogens and androgens by catalyzing the reduction of 17-ketosteroids or the oxidation of 17β-hydroxysteroids. The enzyme activities associated with the different 17β-HSD isoforms are widespread in human tissues, not only in classic steroidogenic tissues but also in a large series of peripheral intracrine tissues. Being involved at the en Read More

Histone deacetylases (HDACs) remove acetyl groups from the tails of lysine residues of histone protein in nuclear chromatin and also from acetylated sites in non-histone proteins. HDACs and histone acetyltransferases (HATs) are major influences on the level of cellular protein acetylation, and an imbalance in acetylation levels, particularly under-acetylated (hypoacetylated) histone protein has been associated Read More

Of the thirteen active carbonic anhydrase (CA) isozymes, the transmembrane isoform CA IX has been shown to be linked with carcinogenesis. CA IX presents an ectopic expression in a multitude of carcinomas derived from cervix, uteri, kidney, lung, oesophagus, breast, colon, etc., contrasting with its restricted expression in normal tissues, namely in the epithelia of the gastrointestinal tract. It has been demonstrated that this m Read More

The epidermal growth factor receptor (EGFR) is dysregulated in various tumour types such as glioblastoma multiforme (GBM), breast cancer, ovarian carcinoma, non-small cell lung cancer and other cancers. As the intracellular tyrosine kinase of the EGFR activates signalling cascades leading to cell proliferation, angiogenesis and inhibition of apoptosis, the EGFR represents an attractive target in cancer therapy. In GBM Read More