Taxanes paclitaxel

A higher than expected incidence of CHF is also observed in patients treated with DOX and other cytotoxics (e.g., the taxane paclitaxel) or new generation targeted agents (e.g., the humanized anti-ErbB-2/neu monoclonal antibody trastuzumab) [3]. The cardiotoxic synergism of DOX with taxanes or... 

Taxanes (paclitaxel, docetaxel) are derivatives of yew tree bark (Taxus brevifolia). They stabilize microtubules in the polymerized state leading to nonfunctional microtubular bundles in the cell. Inhibition occurs during G2- and M-phases. Taxanes are also radiosensitizers. Unwanted effects include bone marrow suppression and cumulative neurotoxicity. 

The taxanes, paclitaxel and docetaxel, act by promoting the assembly of microtubules. The taxanes induce cell cycle arrest in the most radiosensitive phase, G2/M thereby promoting radiosensitivity. In vitro studies have also demonstrated apoptosis in cell culture lines with paclitaxel (32). Paclitaxel dose-dependent synergy is also seen in squamous carcinoma cell lines (33). Much literature has been published reg arding the use of taxanes when combined with radiotherapy. 

Fig. 1 Structures of the taxanes paclitaxel (PTX, taxol) and docetaxel (DTX, taxotere)...

The importance of the C-13 substituted phenylisoserine side chain to the bioactivity of paclitaxel has been acknowledged for a long time. It has been shown that the substimtions and/or stereochemistry of C-2, 3, and 3 -N contribute to its activity in different ways. An early report has demonstrated the baccatin core bearing the C-13 side chain in 2 R,3 S form as naturally occurring taxane—paclitaxel are active, whereas three other stereogenic forms are all but inactive. ... 

The taxanes (paclitaxel and docetaxel) are a newer class of agents that rival the anthracyclines in their activity in metastatic breast cancer, becoming (arguably) the most active class of chemotherapy for this disease. Since these agents are relatively new, adjuvant studies including them have not yet been incorporated into the overview metaanalysis. However, results from a few clinical trials have been reported and are reaching substantial follow-up to provide meaningful information. All trials have enrolled node-positive patients only, and all... 

Among all ABC transporters, P-gp, also known as MDRl protein, ABCBl or CD243, is probably the most studied and characterized member. It was first found as a 170-kDa ATP-dependent membrane glycoprotein that acts as a drug efflux pump [15], P-gp is a broad-spectrum transporter, capable of transporting several structurally and functionally unrelated substrate molecules. Its substrates are typically hydrophobic, amphipathic products, including many chemotherapeutic compounds used for cancer treatment, e.g., vinca alkaloids (vincristine, vinblastine), taxanes (paclitaxel, docetaxel), epipodophyllotoxins (etoposide, teniposide), anthracyclines (doxorubicin, daunorubicin, epirubicin), topotecan, dactinomycin, and mitomycin-C [37]. 

Different chemotherapeutic dmgs currently used to treat cancer patients are alkaloids like vincristine and vinblastine or taxanes paclitaxel and docetaxel. Although berberine is still not used in a clinical setting, it also possesses antitumoral activity against a number of tumor types. Indeed, a study using 60 tumor cell lines showed that the IC50 value for berberine was similar to that of other alkaloids used in chemotherapy like paclitaxel or vinblastine [120]. Moreover, in contrast to other antitumoral drugs, the secondary toxicity of berberine is very low as explained in... 

Taxanes Paclitaxel (853 Da) Docetaxel (861 Da) Sinus bradycardia, ventricular arrhythmias, myocardial ischemia, LV dysfunction, enhanced anthracycline cardiotoxicity... 

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