Paclitaxel cancer

Certain drugs bind to microtubules and thus interfere with their assembly or disassembly. These include colchicine (used for treatment of acute gouty arthritis), vinblastine (a vinca alkaloid used for treating certain types of cancer), paclitaxel (Taxol) (effective against ovarian cancer), and griseoflilvin (an antifungal agent). 

Docetaxel is the second representative of the new entity of drugs that have a unique taxane ring in common, such as the one seen in pachtaxel. Being more efficacious than paclitaxel, docetaxel is used in ovarian cancer. Paclitaxel and docetaxel inhibit microtubule depolymerization, thereby reducing the formation of stable microtubule bundles (see also Figure 15). 

Ranganathan S, Benetatos CA, Colamsso PJ et al (1998) Altered beta-tubulin isotype expression in paclitaxel-resistant human prostate carcinoma cells. Br J Cancer 77 562-566... 

F.14 Paclitaxel, which is extracted from the Pacific yew tree Taxus brevifolia, has antitumor activity for ovarian and breast cancer. It is sold under the trade name Taxol. On analysis, its mass percentage composition is 66.11% C, 6.02% H, and 1.64% N, with the balance being oxygen. What is the empirical formula of paclitaxel ... 

The taxanes (e.g., 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. 

Vinorelbine, a microtubule interactive agent, also has shown impressive response rates in metastatic breast cancer.60 Vinorelbine was approved by the FDA in 1994 for the treatment of non-small cell lung cancer. It is not approved for breast cancer, but response rates to vinorelbine range from 30% to 50%, with an overall 5% complete response rate in phase I and phase II studies in patients with advanced breast cancer. Importantly, paclitaxel, docetaxel, and vinorelbine do not appear to be cross-resistant with anthracyclines, which are arguably considered first-line treatment of metastatic breast cancer. 

Armstrong DK, Bundy B, Wenzel L, et al. Intraperitoneal cisplatin and paclitaxel in ovarian cancer. N Engl ] Med 2006 354 34-43. 

Neijt IP, Engelholm SA, Tuxen MK, et al. Exploratory phase III study of paclitaxel and cisplatin versus paclitaxel and carbo-platin in advanced ovarian cancer. J Clin Oncol 2000 18 3084-3092. 

Ozols RF, Bundy BN, Greer BE, et al. Phase III trial of carboplatin and paclitaxel compared with cisplatin and paclitaxel in patients with optimally resected stage III ovarian cancer a gynecologic oncology group study. J Clin Oncol 2003 21 3194-3200. 

Swanton, C., Marani, M., Pardo, O. et al. 2007. Regulators of mitotic arrest and ceramide metabolism are determinants of sensitivity to paclitaxel and other chemotherapeutic drugs. Cancer Cell, 11 (6) 498—512. 

Konecny G,Thomssen C, Luck H, et al. Her-2/neu gene amplification and response to paclitaxel in patients with metastatic breast cancer. J. Natl. Cancer Inst. 2004 96 1141-1151. 

The answer is c. (Hardman, pp 1260—1262.) Paclitaxel is a large structural molecule that contains a 15 membered taxane ring system. This anti cancer agent is an alkaloid derived from the bark of the Pacific yew tree. Its chemotherapeutic action is related to the microtubules in the cell. Paclitaxel promotes microtubule assembly from dimers and causes microtubule stabilization by preventing depolymerization. As a consequence of these actions, the microtubules form disorganized bundles, which decreases... 

Baselge, ]., et al., "Recombinant Humanized Anti-HER2 Antibody (HERCEPTIN) Enhances the Antitumor Activity of Paclitaxel and Doxorubicin Against HER2/neu Overexpressing Human Breast Cancer Xenografts," Cancer Res., 58, 2825-2831 (1998). 

A fine example of such a semi-synthesis is the preparation of the anti-cancer drug paclitaxel (Taxol ), a relatively scarce compound from Taxus brevifolia. Here, the natural and better accessible 10-deacetylbaccatin III, isolated from the leaves of Taxus baccata, provides the complicated ring system of paclitaxel, including all substituents with the right stereostructure (Scheme 5.1). In just four reaction steps [5] paclitaxel is obtained from 10-deacetylbaccatin III. 

Chemotherapeutic agents that have significant cancer response when combined with hyperthermia (up to 43°C) include doxorubicin, melphalan, mitomycin C (MMC), mitoxantrone, gemcitabine, etoposide, and especially the platinum-based agents carboplatin and oxaliplatin (Mohamed et al., 2003 Sugarbaker et al., 2005). Agents that do not work well with hyperthermia include irinotecan, paclitaxel, docetaxel, 5-fluorouracil, and floxuridine (Mohamed et al., 2003 Sugarbaker et al., 2005). 

Huisman MT, Chhatta AA, van Tellingen O, Beijnen JH, Schinkel AH (2005) MRP2 (ABCC2) transports taxanes and confers paclitaxel resistance and both processes are stimulated by probenecid. Int J Cancer 116 824—829. 

Yen WC, Corpuz MR, Prudente RY, Cooke TA, Bissonnette RP, Negro-Vilar A, Lamph WW (2004) A selective retinoid X receptor agonist bexarotene (Targretin) prevents and overcomes acquired paclitaxel (Taxol) resistance in human non-small cell lung cancer. Clin Cancer Res 10(24) 8656-8664. 

A. Gadducci, S. Cosio, A. Fanucchi, V. Nardini, M. Roncella, P.F. Conte, and A.R. Genazzani. Chemotherapy with epirubicin and paclitaxel for breast cancer during pregnancy Case report and review of the literature. Anticancer Res. 23 5225-5229 (2003). 

Kemper EM, van Zandbergen AE, Cleypool C, Mos HA, Boogerd W, Beijnen JH, van Tellingen, O (2003) Increased penetration of paclitaxel into the brain by inhibition of P-glycoprotein. Cbn Cancer Res 9 2849-2855... 

ABI-007 (Abraxane) Albumin-coated nanoparticle paclitaxel tubulin inhibitor Breast cancer Randomized Phase II trial... 

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