Current Cancer Drug Targets - Volume 7, Issue 8, 2007

The tubulin/microtubule system is an integral component of the cytoskeleton. Microtubules are highly dynamic structures that play a critical role in orchestrating the separation and segregation of chromosomes during mitosis. This makes microtubules highly valued as anticancer drug targets. Tubulin-binding agents (also known as anti-microtubule, microtubule-binding, microtubule-targeting drugs) are derived from natural sour Read More

As microtubules are essential in many cell functions, they have been used as a target of a variety of anticancer drugs that are grouped as stabilizing (taxanes) and destabilizing (vinca-alkaloids, colchicinoids) microtubule agents. It appears clearly now that the dynamic behaviour more than modifications of microtubule mass are altered by antitubulin agents in the range of serum concentrations obtained after administr Read More

Vinca alkaloids and taxanes represent the mainstay of medical treatment of hematological and solid tumors. Unfortunately, a major clinical problem with these agents is drug resistance. Although a plethora of mechanisms of drug resistance have been described, only a few of them have been validated in clinical trials. Among these, the one involving the protein TUBB3 seems to represent a promising target for studying dr Read More

Microtubule-Targeting Agents (MTAs) constitute a class of drugs largely used in cancer treatment. Among them, both taxanes and Vinca-alkaloids are known to inhibit cancer cell proliferation by inducing cell cycle arrest and subsequent apoptosis. These agents modify the cytoskeleton by affecting the tubulin/microtubule system. In cancer cells, both classes suppress microtubule dynamics through inhibition of microtubule Read More

The importance of microtubules in mitosis makes them a superb target for a group of highly successful, chemically diverse anticancer drugs. Knowledge of the mechanistic differences among the many drugs of this class is vital to understanding their tissue and cell specificity, the development of resistance, the design of novel improved drugs, optimal scheduling of treatment, and potential synergistic combinations Read More

Current cancer chemotherapeutic drugs have limited efficacy due to the fact that tumour cells are a rapidly changing target characterised by genomic instability. Unlike tumour cells, activated endothelial cells (ECs) required for angiogenesis, a process indisputably crucial to tumour growth and metastasis, were originally considered to be ideal therapeutic targets free of drug resistance. Additionally, unlike preclinical studies i Read More

A trend in investigating the use of several nutritional compounds for cancer chemoprevention has revealed that phytochemicals demonstrated anti-cancer properties by inhibiting signal transduction pathways essential for cancer cell proliferation, tumor growth, invasion and metastasis. Emerging evidence suggests that the anti-proliferative and anti-oxidant effects of some of these dietary agents could be utilized to both Read More

With several successful anticancer drugs on the market and numerous compounds in clinical developments, antimitotic agents represent an important category of anticancer agents. However, clinical utility of the tubulin-binding agents is somewhat limited due to multiple drug resistance (MDR), poor pharmacokinetics and therapeutic index. There is ongoing need for the modulators of other intracellular targets that result i Read More

The avoidance of apoptosis is one of the hallmarks of cancer cells. In addition, failure to induce apoptosis by anticancer agents, either due to limitations of the drug or the tumour cell evading apoptosis, is a reason for chemotherapeutic failure. Two general pathways for apoptotic cell death have been characterised, the extrinsic and intrinsic pathways which merge in the final common pathway. X-linked inhibitor of apo Read More

Attempts to control cancer involve a variety of means, including the use of suppressing, blocking and transforming agents. Suppressing agents prevent the formation of new cancers from pro-carcinogens, blocking agents prevent carcinogenic compounds from reaching critical initiation sites, while transformation agents act to facilitate the metabolism of carcinogenic components into less toxic materials or to prevent the Read More