About the book
Multiple myeloma (MM)is a plasma cell malignancy characterized by neoplastic proliferation of clonal plasma cells producing a monoclonal immunoglobulin. Nuclear factor-kappaB (NF-κB) stimulates the transcription of proteins that promote cell survival, growth and reduce susceptibility to apoptosis. This signalling pathway is constitutively activated in MM. Two distinct Wnt pathways (Wnt/β-catenin and Wnt/RhoA) are aberrantly activated in MM. The phosphoinositide 3-kinase (PI3K)/protein kinase B (AKT)/mammalian target of rapamycin (mTOR) signalling pathway is also over induced in MM. Therefore, inhibitors of these signalling pathways are used in the treatment of MM. Autologous stem cell transplantation has been a foremost improvement in MM therapeutics. It is considered the standard of care for all medically fit, newly diagnosed MM patients. Over the past decade, newly introduced therapeutic regimens, mainly proteasome inhibitors and immunomodulatory drugs, have significantly improved treatment outcome and survival of MM.
However, most of these patients relapse, underlining the need for new therapeutic approaches. Immunotherapies using new specific CD38 and CD319 antibodies, Daratumumab and Elotuzumab or Empliciti, checkpoint inhibitors and chimeric antigen receptor-modified T (CAR T) cells therapies will improve the treatment of MM patients. The most recent innovative immunologic approach has been CAR T cells, which have demonstrated the ability to selectively kill cancer cells and also overcome all conventional drug-related resistance mechanisms. Proteolysis targeting chimeric molecule (PROTAC) ARV825 caused ubiquitination of bromodomains resulting in their efficient degradation by proteasome activity. Bromodomain degradation downregulates Myc expression contributing to MM cells growth inhibition. All these items will be discussed in this book.