Targeted therapies

Bagshawe KD (2003) The history of targeted therapy for cancer. In Sharma SK, Harrignton KJ (eds) Targeted therapy for cancer. Oxford University Press, New York, pp 3-16... 

AML represents a group of disorders in which both failure to differentiate and overproliferation in the stem cell compartment produce an overabundance of nonfunctional cells termed myeloblasts. While the specific cause for this biologic abnormality is unknown, an understanding of the genetic influence of leukemia is leading to a wide variety of targeted therapies.9... 

Screening the molecular heterogeneity of receptor expression in endothelial cell surfaces is required for the development of vascular-targeted therapies. First, as opposed to targeting purified proteins as discussed above, membrane-bound receptors are more likely to preserve their functional conformation, which can be lost upon purification and immobilization outside the context of intact cells. Moreover, many cell surface receptors require the cell membrane microenvironment to function so that protein-protein interaction may occur. Finally, combinatorial approaches may allow the selection of cell membrane ligands in a functional assay and without any bias about the cellular surface receptor. Therefore, even as yet unidentified receptors may be targeted. 

Animal modeling of targeted therapies, including pre-clinical PK and PD... 

Standardization of IHC/ICC has been a critical issue for more than three decades, especially with the advances in targeted therapy such as the development of trastuzumab (Herceptin) for advanced breast cancer.51 Nevertheless, standardization is a difficult issue because numerous factors may influence the consistency and reliability of immunostaining results, including fixatives, fixation time, AR, antibody clones, detection system, and interpretation (see Part II). In cytopathology, the situation is even worse due to its variable cell sample preparation techniques. Cytopreparation is. .. the foundation of cytomorphology. 52 We believe it is also the foundation of ICC. Therefore, standardization of ICC needs to start with uniform and reliable cytopreparation. 

Ross JS, Fletcher JA, Bloom KJ, et al. Targeted therapy in breast cancer the HER-2/neu gene and protein. Mol. Cell. Proteomics 2004 3 379-398. 

Goldenberg, D. 2002. Targeted therapy of cancer with radiolabeled antibodies. Journal of Nuclear Medicine 43(5), 693-713. 

Several pro-inflammatory cytokines, such as TNFa, IL-1, IL-6, are important in the initiation and maintenance of various autoimmune diseases, such as RA, CD, and psoriasis. Thus, targeted therapies, which have been developed to inhibit their activity, have resulted in clinical improvement of these patients. Currently, there are three TNFa inhibitors (etanercept, infliximab, and adalimumab) and one IL-1 receptor antagonist (anakinra) that have been approved for the treatment of at least one of these diseases. In addition, a number of other anti-cytokine therapies are in clinical development. The TNFa antagonists will be reviewed here. 

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