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Abstract
Taxanes, mainly paclitaxel and docetaxel, the microtubule stabilizers, have been well known for being the first-line therapy for breast cancer for more than the last thirty years. Moreover, they have been also used for the treatment of ovarian, hormone-refractory prostate, head and neck, and non-small cell lung carcinomas. Even though paclitaxel and docetaxel significantly enhance the overall survival rate of cancer patients, there are some limitations of their use, such as very poor water solubility and the occurrence of severe side effects. However, this is what pushes the research on these microtubule-stabilizing agents further and yields novel taxane derivatives with significantly improved properties. Therefore, this review article brings recent advances reported in taxane research mainly in the last two years. We focused especially on recent methods of taxane isolation, their mechanism of action, development of their novel derivatives, formulations, and improved tumor-targeted drug delivery. Since cancer cell chemoresistance can be an unsurpassable hurdle in taxane administration, a significant part of this review article has been also devoted to combination therapy of taxanes in cancer treatment. Last but not least, we summarize ongoing clinical trials on these compounds and bring a perspective of advancements in this field.
Highlights
Cancer represents a long-time burden and, despite great progress in the knowledge of this disease, a detailed understanding of it is still lacking, which reduces the success of the treatment of more serious cases
In their study on patients with non-small cell lung carcinoma, they identified two sites in the ABCB1 gene, the mutations of which significantly correlated with enhanced cytotoxicity after taxane treatment
Despite giant leaps made in cancer therapy over the last decades, taxanes remain one of the most clinically used groups of cancer therapeutics
Summary
Cancer represents a long-time burden and, despite great progress in the knowledge of this disease, a detailed understanding of it is still lacking, which reduces the success of the treatment of more serious cases. Besides optimizing fungal growth conditions, an effective approach leading to augmented paclitaxel yields from fungi might be the use of certain elicitors or effectors of the cellular processes in fungi For this purpose, Subban et al [16] confirmed the efficacy of salicylic acid on Pestaloptiosis microspora, which is one of the fungal species most commonly known for taxane production. As discussed above, since paclitaxel isolation from raw yew material is a very ecologically demanding process and production in other organisms is not cost-effective, total paclitaxel synthesis would be a vital option Multiple such synthetic approaches have been described; none of them has been used commercially, so far [30,31,32,33,34,35,36,37,38,39,40,41]. Utilizing 10-DAB from the tree needles is beneficial, since they regrow and, harvesting of whole trees is not necessary which results in less impact on the environment [45]
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