By Esteban Braggio Ph.D., Rafael Fonseca M.D. (auth.), Nikhil C. Munshi, Kenneth C. Anderson (eds.)
Despite the advances in traditional, novel agent and excessive dose chemotherapy a number of myeloma (MM) is still incurable. with a view to conquer resistance to present treatments and enhance sufferer consequence, novel biologically-based therapy methods are being built. present translational study in MM targeting the advance of molecularly-based mixture cures has nice promise to accomplish excessive frequency and sturdy responses within the majority of sufferers. significant advances are making this aim attainable. First, fresh advances in genomics and proteomics in MM have allowed for elevated realizing of ailment pathogenesis, pointed out novel healing pursuits, allowed for molecular type, and supplied the clinical intent for combining detailed remedies to extend tumor telephone cytotoxicity and abrogate drug resistance. moment, there's now an elevated figuring out of ways adhesion of MM cells in bone marrow (BM) additional affects gene expression in MM cells, in addition to in BM stromal cells (BMSCs). because of those advances in oncogenomics at the one hand and elevated realizing of the position of the BM within the pathogenesis of MM at the different, a brand new therapy paradigm focusing on the tumor mobile and its BM microenvironment to beat drug resistance and enhance sufferer consequence has now been built. Thalidomide, lenalidomide, and Bortezomib are 3 brokers which aim the tumor mobile in its microenvironment in either laboratory and animal versions and that have swiftly translated from the bench to the bedside. Ongoing efforts are utilizing oncogenomics and mobile signaling stories to spot subsequent new release of remedies in MM at the one hand, and to notify the layout of blend trials at the different. This new paradigm for overcoming drug resistance and enhancing sufferer end result in MM has nice promise not just to alter the ordinary heritage of MM, but in addition to function a version for detailed therapeutics directed to enhance end result of sufferers with MM.
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Additional info for Advances in Biology and Therapy of Multiple Myeloma: Volume 1: Basic Science
Tiedemann RE, Gonzalez-Paz N, Kyle RA et al (2008) Genetic aberrations and survival in plasma cell leukemia. Leukemia 22:1044–1052 77. Mazars GR, Portier M, Zhang XG et al (1992) Mutations of the p53 gene in human myeloma cell lines. Oncogene 7:1015–1018 78. Sawyer JR, Tricot G, Mattox S, Jagannath S, Barlogie B (1998) Jumping translocations of chromosome 1q in multiple myeloma: evidence for a mechanism involving decondensation of pericentromeric heterochromatin. Blood 91:1732–1741 22 E. Braggio and R.
Global GEP of polyclonal plasma cells and healthy bone marrow plasma cells derived from immunomagnetic sorting has revealed not only strong similarities but also distinct and reproducible differences between the two populations and myeloma cells [15, 16], suggesting that polyclonal plasma cells may not fully recapitulate the molecular biology of a bone marrow plasma cell. 2 Early GEP-Based Studies Early studies made several contributions to understanding the molecular basis of MM by comparing gene-expression proﬁles of CD138-enriched plasma cells from the bone marrow of healthy donors and patients with monoclonal gammopathy of undetermined signiﬁcance (MGUS), newly diagnosed MM, and end-stage MM .
1 Historical Perspective It is very likely that each of the six hallmarks of cancer, outlined in the Hanahan– Weinberg model , ultimately causes or is related to reproducible changes in the expression of subsets of genes within clonal cancer cells and that these patterns are S. Usmani • B. D. Shaughnessy, Jr. C. C. 1007/978-1-4614-4666-8_3, © Springer Science+Business Media New York 2013 41 42 S. Usmani et al. exclusive and speciﬁc to each malignancy. This hypothesis was difﬁcult to test, however, until the completion of the human genome project [2, 3] and the development of high-throughput tools capable of analyzing the activities of all genes simultaneously .