Download PDF by Ross Brown, P. Joy Ho, John Gibson, Douglas Joshua (auth.),: Advances in Biology and Therapy of Multiple Myeloma: Volume

By Ross Brown, P. Joy Ho, John Gibson, Douglas Joshua (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. on the way to conquer resistance to present treatments and enhance sufferer end result, novel biologically-based therapy techniques are being constructed. present translational examine in MM concentrating on the improvement 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 objective attainable. First, fresh advances in genomics and proteomics in MM have allowed for elevated knowing of ailment pathogenesis, pointed out novel healing objectives, allowed for molecular class, and supplied the medical intent for combining certain treatments to extend tumor telephone cytotoxicity and abrogate drug resistance. moment, there's now an elevated knowing of the way adhesion of MM cells in bone marrow (BM) extra 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 function of the BM within the pathogenesis of MM at the different, a brand new remedy paradigm focusing on the tumor cellphone and its BM microenvironment to beat drug resistance and enhance sufferer consequence has now been constructed. Thalidomide, lenalidomide, and Bortezomib are 3 brokers which objective the tumor cellphone in its microenvironment in either laboratory and animal types and that have quickly translated from the bench to the bedside. Ongoing efforts are utilizing oncogenomics and mobilephone signaling reviews to spot subsequent iteration of treatments 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 consequence in MM has nice promise not just to alter the average background of MM, but additionally to function a version for special therapeutics directed to enhance consequence of sufferers with MM.

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Additional resources for Advances in Biology and Therapy of Multiple Myeloma: Volume 2: Translational and Clinical Research

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Science 254:279–282 26. Hong S, Qian J, Yang J, Li H, Kwak LW, Yi Q (2008) Roles of idiotype-specific t cells in myeloma cell growth and survival: Th1 and CTL cells are tumoricidal while Th2 cells promote tumor growth. Cancer Res 68:8456–8464 27. Wen YJ, Barlogie B, Yi Q (2001) Idiotype-specific cytotoxic T lymphocytes in multiple myeloma: evidence for their capacity to lyse autologous primary tumor cells. Blood 97:1750–1755 28. Bergenbrant S, Yi Q, Osterborg A, Bjorkholm M, Osby E, Mellstedt H, Lefvert AK, Holm G (1996) Modulation of anti-idiotypic immune response by immunization with the autologous M-component protein in multiple myeloma patients.

Moreover, the proportion of individuals who had an idiotypespecific response of the T helper-1 (Th1)-type (IFN-g- and/or IL-2-secreting cells) [22, 23] was significantly higher in patients with indolent disease (MGUS and MM stage I) compared with those with advanced MM (stage II/III). In contrast, cells secreting the Th2-subtype cytokine profile (IL-4 only) [22, 23] were seen more frequently in patients with advanced MM (stage II/III) [15]. A similar pattern of cytokine secretion was also reported by others [24].

Recombinant human DKK1 or bone marrow serum containing an elevated level of DKK1 inhibited the differentiation of osteoblast precursor cells in vitro. Furthermore, anti-DKK1 antibody treatment was associated with reduced tumor growth in myeloma mouse models [47–49]. These results indicate that DKK1 is an important player in myeloma bone disease. The identification of novel tumor-associated antigens, particularly those shared among patients, is urgently needed to improve the efficacy of immunotherapy for MM.

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