Current Cancer Drug Targets - Volume 4, Issue 2, 2004

Cancer drugs have traditionally been identified in screens designed to produce broad biological end points such as cell death. A serious undesired outcome of drugs discovered in these screens is that the mechanism of drug action is unknown and such drugs often have adverse side effects. Designing cancer drugs that act on specific targets offer the advantage that the mechanism of drug action can be understood and accu Read More

Protein kinase C (PKC) comprises a family of isozymes (α, βI, βII,γ δ, ε, θ,& eegr;, λ/ι [mouse/human], and ζ) which are involved in signal transduction from membrane receptors to the nucleus. Activation of PKC by phorbol esters promotes tumor formation, and from that it was concluded that inhibitors of PKC might prevent carcinogenesis or inhibit tumor proliferation. However, the situation is more complicated Read More

In normal healthy tissues, an equilibrium is established between cell death and survival. This equilibrium ensures that cells survive in the right milieu, but undergo programmed cell death (apoptosis) when damaged, or when the environment is no longer supportive. Diseases may occur with alterations in this homeostasis. For example, cancer cells may survive in an environment in which they would not normally exist. This is a Read More

The Transforming Growth Factor-β (TGFβ) superfamily of cytokines is comprised of a number of structurally-related, secreted polypeptides that regulate a multitude of cellular processes including proliferation, differentiation and neoplastic transformation. These growth regulatory molecules induce ligandmediated hetero-oligomerization of distinct type II and type I serine / threonine kinase receptors that transmit signals pred Read More

Inhibitors of estrogen-related pathways have been used with some success in the treatment of breast cancer. These include the antiestrogens tamoxifen, more recently faslodex, and the aromatase inhibitor anastrazole. However, failure and recurrence rates are substantial with drugs countering the effects of estrogens. Progestins, unlike estrogens, have generally been considered to oppose breast cancer and have be Read More

The fluoropyrimidines were first synthesised nearly 50 years ago as rationally designed anti-cancer agents. Their target was pyrimidine and hence DNA synthesis. 5-Fluorouracil has been the most extensively used in a wide variety of malignancies. In more recent years a fuller understanding of the pharmacokinetics of these agents has lead to their utilisation as more effective and versatile anti-cancer drugs than might have bee Read More

The histone deacetylase inhibitors are a new class of cytostatic agents that inhibit the proliferation of tumor cells in culture and in vivo by inducing cell cycle arrest, differentiation and / or apoptosis. Histone acetylation and deacetylation play important roles in the modulation of chromatin topology and the regulation of gene transcription. Histone deacetylase inhibition induces the accumulation of hyperacetylated nucleoso Read More

The human genome contains a unique class of domains, referred to as AT islands, which consist typically of 200-1000 bp long tracts of up to 100% A / T DNA. The significance of AT islands as potential targets for chemotherapeutic intervention stems from two main aspects. First, AT islands are inherently unstable (expandable) minisatellites that are found in various known loci of genomic instability, such as ATrich fragile sites. Se Read More