Anti-cancer therapy

Catharanthus roseus) [9]. Maytansine (3) is an ansa macrolyde isolated from Maytenus ovatus [10], and rhizoxin (4) is an antitumor macrolide isolated from the fungus Rhizopus chinensis [11]. Another very important tubulin interactive anti-cancer agent is colchicine (6), and this compound binds to a different binding site of tubulin but is also used in anti-cancer therapy. 

Following the synthesis of the sodium, potassium, and succinic acid esters of CA-4, which were not soluble in water [35], CA-4P (9), the disodium phosphate pro-drug was developed and is currently in phase II of clinical trials [36]. CA-4P is a promising candidate for combination anti-cancer therapy because it is inactive as a phosphate but is rapidly hydrolyzed in vivo to the active CA-4, 7 compound [31,37]. 

Strategies to Target Change in Anti-Cancer Therapies by Finding Agents That Can Potentially Perturb an Unstable Pathway... 

Most notably, compounds clustered in clades P4 and M3 are associated only with up pathways, and those in clades N9, Pe, Fe, Fs, and Vi are associated predominantly with down pathways and with very few or no up pathways. Most clinically used compounds in anti-cancer therapies are located in regions M and S, essentially targeting the proliferation stage of a cancer cell. Our analysis, however, points to a much more... 

The adverse event needs to be clinically significant enough that the risk-benefit of therapy is percieved to be altered. In this regard, the acceptable risk-benefit profile of anti-cancer therapies is markedly diflFerent than, for example, that of anti-hypertension therapy. 

Moreover gene-expression analysis of leukemia cells from B-lineage acute lymphoblastic leukemia pediatric patients has identified sets of differentially expressed genes that are associated specifically with sensitivity or resistance to chemotherapy. Such information can also be used in diagnostic assay to stratify the patients in sub-categories, to develop new drugs and later on to personalize the anti-cancer therapy. 

The results of these preclinical tumor studies revealed that distant primary and metastatic tumors may be treated by i.m. injection of a therapeutic pDNA. This type of anti-cancer therapy could be useful for the treatment of human neoplasms. One advantage of this type of therapy is that tumors in organs that are difficult to access may be treated by a simple i.m. injection. The therapy may also prevent the growth and spread of metastases. 

The first two DES to be commercialized incorporated sirolimus (rapamycin Rapamune , Wyeth Pharmaceuticals, Inc, Collegeville, Pennsylvania, U.S.A.), an immunosuppressive agent used for the prevention of transplanted organ rejection, or paclitaxel (Taxol , Bristol-Myers Squibb, Princeton, New Jersey, U.S.A.) an agent with an extensive history as an anti-cancer therapy. 

Tzukerman M, Skorecki KL. A novel experimental platform for investigating cancer growth and anti-cancer therapy in a human tissue microenvironment derived from human embryonic stem cells. Meth Mol Biol 2006 331 329-46. 

Micke, P. and Ostman, A. (2004) Tumour-stroma interaction cancer-associated fibroblasts as novel, targets in anti-cancer therapy Lung Cancer 45 (Suppl. 2), S163-S175. 

Ryan BM, O Donovan N, Duffy MJ (2009) Survivin a new target for anti-cancer therapy. Cancer Treat Rev 35(7) 553-562... 

To conclude, there is substantial evidence for an important role of SPHKl in tumor cell survival, suggesting this enzyme as a drug target in anti-cancer therapy (see also Cuvihier, 2007, for a detailed review). To support this further, there is also literature demonstrating that SPHKl inhibition can sensitize cells... 

Following detection of the antiviral activity of hypericin 1 (see above), a number of observations have suggested that this compound may as well represent a potential anti-cancer therapy. These biological properties include the light-dependent inhibition of protein kinase C [142], the photosensitized inhibition of mitochondrial succinoxidase [143], and the photoinduced inhibition of epidermal growth factor receptor (EGF-R) tyrosine kinase activity [144]. 

FIGURE 29.4 Pycnogenol is in theory able to contribute to the protection from cancer at three different levels at a preventive level, as a specific modulator of cellular functions, and as adjuvant in anti cancer therapy. On the top of these activities interplaying one another, Pycnogenol also possibly... 

Efferth, T. (2005). Mechanistic Perspectives for 1,2,4-trioxanes in Anti-cancer Therapy. Drug Resistance. Updat, Vol. 8, No.1-2, (February 2005), pp. 85-97, ISSN 1368-7646 Ferreira, M. (2002). Multivariate QSAR. Journal of the Brazilian Chemical Society, Vol.13, No. 6, (November/December 2002), pp. 742-753, ISSN 1678-4790 Fujita, T. (1995). QSAR and Drug Design New Developments and Applications, Elsevier, ISBN 0-444-88615-X, Amsterdan, The Netherlands... 

For more on molecular aspects of anti-cancer therapy, see alkylating agents (Section 13.4), and Neidle and Waring (1983). 

Attempts are being made to find agents that will rupture the membranes of cancer cells selectively. For example amines, stich as 4-dodecylpyridine 14.20), with a pX a value between 5 and 9, are selectively accumulated by lysosomes because these have an acidic sap, as have cancer cells (p. 151). The amines enter the cells freely, being non-ionized and lipophilic, but are trapped as cations by the acidic sap and cannot escape. Because the cations (but not the neutral species) are detergents, the lysosomal membranes become ruptured, and it is hoped to adapt this phenomenon to anti-cancer therapy. 4-Dodecylpyridine is non-toxic to mice after intraperitoneal injection of 0.5 g/kg (Firestone, Pisano and Bonney, 1979). 

Keefe, D.M.K. and Gibson, R.J. 2007. Mucosal injury from targeted anti-cancer therapy. Support Care Cancer, 15 483—490. 

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