Anticancer therapeutics: a surge of new developments increasingly target tumor and stroma.

The Annual Meeting of the American Association for Cancer Research (AACR) brings together research in fundamental biology, translational science, drug development and clinical testing of emerging anticancer therapies. Among the highlights of the 2007 Annual Meeting were major research themes on drug action, drug resistance and new drug development. Instead of striving for a comprehensive overview, we showcase several trends, concepts and research areas that exemplify the complexity of drug resistance and its reversal as we currently understand it. Many of the studies discussed here deal with the interaction of tumor cells with their stromal microenvironment; structural proteins as well as cellular components, fibroblasts as well as inflammatory cells. Target identification, target validation and dealing with the challenge of resistance are recurring themes. Specific classes of molecules discussed are the taxanes, tyrosine kinase inhibitors, anti-angiogenic, anti-stromal and anti-metastatic agents. In the latter three categories, targets reviewed are delta-like ligand 4 (DLL4), integrins, nodal, galectins, lysyl oxidases and thrombospondins, several of which belong to the p53-tumor suppressor repertoire of secreted proteins. Finally, developments in other inhibitor classes such as PI3K/Akt and Rho GTPase inhibitors and thoughts on possible novel combination therapies are briefly summarized. The report also includes relevant publications to July 2007.