caa a22 4500 605542864 CHVBK 20210128100923.0 cr unu---uuuuu 210128e20150101xx s 000 0 eng 10.1007/s00109-014-1226-2 doi (NATIONALLICENCE)springer-10.1007/s00109-014-1226-2 Meaningful prevention of breast cancer metastasis: candidate therapeutics, preclinical validation, and clinical trial concerns [Elektronische Daten] [Alexandra Zimmer, Patricia Steeg] The development of drugs to treat breast and other cancers proceeds through phase I dose finding, phase II efficacy, and phase III comparative studies in the metastatic setting, only then asking if metastasis can be prevented in adjuvant trials. Compounds without overt cytotoxic activity, such as those developed to inhibit metastatic colonization, will likely fail to shrink established lesions in the metastatic setting and never be tested in a metastasis prevention scenario where they were preclinically validated. We and others have proposed phase II primary and secondary metastasis prevention studies to address this need. Herein, we have asked whether preclinical metastasis prevention data agrees with the positive adjuvant setting trials. The data are limited but complimentary. We also review fundamental pathways involved in metastasis, including Src, integrins, focal adhesion kinase (FAK), and fibrosis, for their clinical progress to date and potential for metastasis prevention. Issues of inadequate preclinical validation and clinical toxicity profiles are discussed. Springer-Verlag Berlin Heidelberg (outside the USA), 2014 Fibrosis nationallicence Focal adhesion kinase (FAK) nationallicence Integrins nationallicence Src nationallicence Breast cancer nationallicence Clinical trials nationallicence Metastasis nationallicence Zimmer Alexandra Women's Malignancies Branch, Center for Cancer Research, National Cancer Institute, 20892, Bethesda, MD, USA aut Steeg Patricia Women's Malignancies Branch, Center for Cancer Research, National Cancer Institute, 20892, Bethesda, MD, USA aut Journal of Molecular Medicine Springer Berlin Heidelberg 93/1(2015-01-01), 13-29 0946-2716 93:1<13 2015 93 109 https://doi.org/10.1007/s00109-014-1226-2 text/html Onlinezugriff via DOI BK010053 XK010053 XK010000 Metadata rights reserved Springer special CC-BY-NC licence nationallicence 1 review-article jats NATIONALLICENCE NATIONALLICENCE NL-springer NATIONALLICENCE 856 40 https://doi.org/10.1007/s00109-014-1226-2 text/html Onlinezugriff via DOI NATIONALLICENCE 700 1- Zimmer Alexandra Women's Malignancies Branch, Center for Cancer Research, National Cancer Institute, 20892, Bethesda, MD, USA aut NATIONALLICENCE 700 1- Steeg Patricia Women's Malignancies Branch, Center for Cancer Research, National Cancer Institute, 20892, Bethesda, MD, USA aut NATIONALLICENCE 773 0- Journal of Molecular Medicine Springer Berlin Heidelberg 93/1(2015-01-01), 13-29 0946-2716 93:1<13 2015 93 109