Holding a similar view, Ruth Sager, a leader in cancer genetics wrote in one of her last articles before her untimely departure that the oncogenes and tumor suppressor genes known at that time, “affect principally cell cycle regulation. None are

known to affect invasion or metastasis”. These genes “do not begin to account for the diversity of cancer phenotypes” [113]. Sager recommended shifting the focus from DNA to RNA i.e. to expression genetics of cancer. She also advocated the “grouping of cancer genes into two classes: class I genes are mutated or deleted, whereas class II genes are not altered at the DNA level. Rather they affect LGX818 clinical trial the phenotype by expression changes”. Class 2 cancer genes are those controlled by the microenvironment. A similar view was expressed, 7 years later, by Vogelstein and Kinzler [114]. They indicated that the late stages of cancer are not specifically associated with abnormalities in cancer genes (i.e. oncogenes and

tumor suppressor genes). The multitude of microenvironmental factors, their enormous activity spectrum and the complexity of CCI-779 cell line their intermolecular cross talk obviously requires an interactive and interdisciplinary exchange between researchers engaged in this research domain. A group of investigators thought to promote such interactions at the international level by organizing meetings dedicated exclusively to TME. The first “International Conference on Tumor Microenvironment: Progression, Therapy, Prevention” was held in Israel on the shore of the Sea of Galilee in 1995. Among the 250 participants were several who participate in the present conference. The Sea of Galilee meeting was a truly multidisciplinary event where the focal issue,

the TME, was Transmembrane Transporters inhibitor approached and discussed thoroughly by specialists from a wide spectrum of biomedical sciences. The 1995 conference was the impetus to establish the International Cancer Idelalisib solubility dmso Microenvironment Forum (ICMF). The forum was founded by an international group of about twenty cancer researches from ten countries. These scientists who were joined a few years later by additional scientists became the “charter member” group of ICMF. Informal charter member meetings were held in London (1997—hosted by Frances R. Balkwill, Imperial Cancer Research Fund); Pittsburgh, (1999—hosted by Theresa L. Whiteside and Ronald B. Herberman, University of Pittsburgh Cancer Institute), San Sebastian, (2003—hosted by Fernando Vidal-Vanaclocha, Basque Country University, School of Medicine) and in Safed (2008—hosted by the Israeli Charter Members). Present in these meetings were charter members and some invited guests. These informal meetings were devoted mainly to discussions on recent results of studies connected with the TME. One of the resolutions of the 2003 San Sebastian charter member meeting was to upgrade ICMF.