antioxidants and renin-angiotensin system inhibitors have met with limited success due, not only, to side effects but also because of their negative interactions with doxorubicin. While aiming to reduce the cardiotoxic effects of anthracyclines using adjunct therapies, it is imperative to assess the effects in cancer cell line to ascertain the clinical utility of such treatments. Interestingly, recent studies using the phosphodiesterase-5 inhibitors sildenafil or tadalafil have shown promise by showing a reduction in the cardiotoxic effects of doxorubicin without affecting its anti-cancer activity. Cell death pathways activated by doxorubicin treatment usually involve the mitochondria to initiate apoptosis or necrosis.Thus, bortezomib is a promising treatment in Bcr-Abl-positive leukemias. An interesting study suggested that bortezomib in 146368-16-3 combination with the cyclin-dependent kinase inhibitor flavopiridol synergizes to induce apoptosis in CML cells. Flavopiridol causes an inhibition of the cell cycle in G1 or G2, based on the inhibition of CDK. Other studies have shown that leukemic cells are particularly sensitive when survival pathway inhibitors are combined with mitotic inhibitors. Moreover, combination of bortezomib with mitotic inhibitors are currently in clinical trials for the treatment of non-small-cell lung carcinoma and other solid tumors. Thus, we hypothesized that a strategy based on the combined treatment with bortezomib and mitotic inhibitors for the treatment of Bcr-Abl-positive leukemias may be promising. Especially important might be to determine the effectiveness of this strategy in TKIs-resistant Bcr-Abl-positive cases. Paclitaxel, a mitotic inhibitor drug acting by stabilization of microtubules, is FDA approved for the treatment of lung, ovarian, breast cancers and advanced forms of Kaposi��s sarcoma. Paclitaxel is now in clinical trials for the treatment of CML. 888216-25-9 biological activity However, to our knowledge, there are no clinical trials or publish
