Díaz Pereira, José Fernando
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Despite considerable progress in its early diagnosis and treatment, cancer continues to be one of the major health and socio-economic problems. Although most cancers start as a localized tumour, metastasis turns it into a systemic disease. Treatment with a chemical substance able to kill the undesired “parasite” (in this case the patient’s own tumoural cells) without affecting the healthy cells, is an obvious method to fight a systemic disease. Unfortunately, although more than 90 different drugs are approved for the treatment of cancer, the results of cancer chemotherapy are far from satisfactory. Although most of the tumours respond favourably to treatment, they develop resistance to the drug after the initial response, leading to the patient’s death.
In the last years the search for new antitumourals has focused on a search for inhibitors of signal transduction. Although these therapeutic agents, such as kinase inhibitors, show spectacular results in the early stages of treatment and have the advantage of a low toxicity over the classical chemotherapeutic agents, they have one weak point. Signal transduction in cells is redundant (Figure 1) and while blocking of the defective activated pathway leads to rapid remission of the tumour, the tumoural cells often find an alternative pathway to grow, leading to relapse of a resistant form of the tumour. Combined treatments involving different kinase inhibitors have been developed with good results; however the development of resistance is shadowing the expectations placed on these magic bullets.
Antitumoural agents targeting tubulin show high systemic toxicity due to their lack of specificity. In spite of their great efficacy in the treatment of solid or blood cancers, this toxicity compromises the treatments based on this agents. However, these compounds also have an advantage over the kinase inhibitors. Since they block tubulin, which is involved in several essential cell functions and is a major constitutive protein, there is no possible alternative pathway to substitute for the functions of tubulin.
The group of microtubule stabilizing agents works to find ways to allow the design of compounds active against tumoural cells that have developed resistance against this type of compounds.