Development and assessment of conventional and targeted drug combinations for use in the treatment of aggressive breast cancers. Export

@article{citeulike:3290462, abstract = {Combination chemotherapy has been at the forefront of cancer treatment for over 40 years. However, the rationale for selecting drug combinations and the process used to demonstrate clinical effectiveness has primarily followed trial and error methodology. Typically, the selection and assessment of combined drug therapies has been based on the effectiveness of each agent as monotherapy in treating the neoplasm and avoiding overlapping toxicities, followed by clinical trials to establish dose scheduling, toxicity, and efficacy. Unfortunately, this scheme is inefficient in terms of the time required to complete and revise these clinical trials based on the outcome to optimize the drug combination. A more rational approach for the development of combination oncology products should consider (i) in vitro assays for assessing therapeutic effects of drug combinations (antagonistic, additive or synergistic interactions) when added simultaneously; (ii) methods for measuring these interactions in vivo; (iii) the importance of understanding pharmacokinetic and biodistribution parameters when using drug combinations; (iv) the need to assess pathways known to contribute to cancer cell survival as well as metastasis; and (iv) the need to assess the fate of different cell populations (cancer and stroma) contributing to the development of cancer. Therefore, the goal of this article is to provide a road map for the preclinical development of drug combination products that will have improved therapeutic activity and a high likelihood of providing beneficial therapeutic outcomes in patients with aggressive cancers with a specific focus on patients with breast cancer.}, address = {Investigational Drug Program, BC Cancer Agency, 675 West 10th Avenue, Vancouver, BC, V5Z 1L3, Canada. dwater@bccrc.ca}, author = {Waterhouse, D. N. and Gelmon, K. A. and Klasa, R. and Chi, K. and Huntsman, D. and Ramsay, E. and Wasan, E. and Edwards, L. and Tucker, C. and Zastre, J. and Wang, Y. Z. and Zhang, Y. Z. and Yapp, D. and Dragowska, W. and Dunn, S. and Dedhar, S. and Bally, M. B.}, citeulike-article-id = {3290462}, citeulike-linkout-0 = {http://view.ncbi.nlm.nih.gov/pubmed/17017873}, citeulike-linkout-1 = {http://www.hubmed.org/display.cgi?uids=17017873}, issn = {1873-5576}, journal = {Current cancer drug targets}, keywords = {assessment, breast, cancer, chemotherapy, review, toxicities, yvonne}, month = {September}, number = {6}, pages = {455--489}, posted-at = {2008-09-18 21:08:46}, priority = {2}, title = {Development and assessment of conventional and targeted drug combinations for use in the treatment of aggressive breast cancers.}, url = {http://view.ncbi.nlm.nih.gov/pubmed/17017873}, volume = {6}, year = {2006} }

TY - JOUR ID - citeulike:3290462 L3 - citeulike-article-id:3290462 N2 - Combination chemotherapy has been at the forefront of cancer treatment for over 40 years. However, the rationale for selecting drug combinations and the process used to demonstrate clinical effectiveness has primarily followed trial and error methodology. Typically, the selection and assessment of combined drug therapies has been based on the effectiveness of each agent as monotherapy in treating the neoplasm and avoiding overlapping toxicities, followed by clinical trials to establish dose scheduling, toxicity, and efficacy. Unfortunately, this scheme is inefficient in terms of the time required to complete and revise these clinical trials based on the outcome to optimize the drug combination. A more rational approach for the development of combination oncology products should consider (i) in vitro assays for assessing therapeutic effects of drug combinations (antagonistic, additive or synergistic interactions) when added simultaneously; (ii) methods for measuring these interactions in vivo; (iii) the importance of understanding pharmacokinetic and biodistribution parameters when using drug combinations; (iv) the need to assess pathways known to contribute to cancer cell survival as well as metastasis; and (iv) the need to assess the fate of different cell populations (cancer and stroma) contributing to the development of cancer. Therefore, the goal of this article is to provide a road map for the preclinical development of drug combination products that will have improved therapeutic activity and a high likelihood of providing beneficial therapeutic outcomes in patients with aggressive cancers with a specific focus on patients with breast cancer. IS - 6 JF - Current cancer drug targets SN - 1873-5576 AD - Investigational Drug Program, BC Cancer Agency, 675 West 10th Avenue, Vancouver, BC, V5Z 1L3, Canada. dwater@bccrc.ca EP - 489 TI - Development and assessment of conventional and targeted drug combinations for use in the treatment of aggressive breast cancers. VL - 6 SP - 455 KW - assessment KW - breast KW - cancer KW - chemotherapy KW - review KW - toxicities KW - yvonne AU - Waterhouse, DN AU - Gelmon, KA AU - Klasa, R AU - Chi, K AU - Huntsman, D AU - Ramsay, E AU - Wasan, E AU - Edwards, L AU - Tucker, C AU - Zastre, J AU - Wang, YZ AU - Zhang, YZ AU - Yapp, D AU - Dragowska, W AU - Dunn, S AU - Dedhar, S AU - Bally, MB PY - 2006/09// UR - http://view.ncbi.nlm.nih.gov/pubmed/17017873 ER -