Rgeted therapeutics acting on specific molecular targets. For instance, it has
Rgeted therapeutics acting on specific molecular targets. For instance, it has been reported that growth factor signals are mutated in a number of cancers including colorectal cancer [15]. Advances in microarray technology have opened the possibility of focusing current research efforts on the development of novel agents capable of targeting key proteins such as phosphatidylinositol-3-kinase (PI3K) and chaperone HSP90, acting in growth factor signaling pathways. Paul Clarke (Surrey, UK) highlighted how DNA microarray technology holds great Enzastaurin cost potential for elucidating gene expression patterns underling the complex cellular effects and mechanisms of action of targeted cancer therapeutics, thus enhancing the opportunities for discovery and development of several PubMed ID:https://www.ncbi.nlm.nih.gov/pubmed/28380356 types of anticancer agents. Although there is circumstantial evidence that the activation of the anti-tumor immune response may be critical in affecting the natural or treatment-induced history of cancer, the complex interactions underling this phenomenon remains largely unknown [16]. For instance, it is still unclear whether factors related to the genetic background of patients are predominant or whether distinct characteristics of individual tumors may facilitate or inhibit immune responses during therapy. The advancement of microarray technology exerted a significant impact on the understanding of crucial factors affecting response to therapy [17]. Francesco M. Marincola (Bethesda, MD, USA) pointed out that current technologies allow genome wide analyses of tumor/host interactions at the tumor site that can be evaluated in the context of the genetic background of individual patients. For instance, microarray analysis applied to serial sampling of tumor lesions may allow the identification of biomarkers predictive of immune responsiveness to a given treatment. In addition, serialsampling of the same lesions using fine needle aspirates before and during treatment may provide information about the mechanisms of action of the treatment and its biological effects. Marincola also described a study aimed at characterizing the mechanisms by which systemic administration of high-dose interleukin-2 (IL-2) was effective for the treatment of metastatic melanoma. Microarray analysis profiled early transcriptional changes in circulating mononuclear cells and in the microenvironment of melanoma metastases. Interestingly, it was established that although this cytokine has minimal effects on migration, activation and proliferation of T cells at the tumor site, it induces a massive production of innate immune effector molecules such as chemoattractants and cytotoxic mediators, likely released by monocytes and NK cells. Moreover, a substantial activation of genes involved in inflammation was reported in the peripheral blood of the same patients [18]. In another study, Eleonora Aric?(Rome, Italy) described how DNA microarrays were used for the profiling gene expression induced in peripheral blood mononuclear cells by IFN- administered to stage IV melanoma patients in combination with epitope-specific immunization. Aric?showed that IFN- induced a well-defined “IFN signature”, which included not only the typical IFN-induced genes, but also several genes typically involved in the immune response. Of note, a defined set of the genes up-regulated in PBMC of the IFN-treated melanoma patients was consistently similar to the genes whose expression was up-regulated in dendritic cells generated after a 3-day i.