New targets and treatments in multiple myeloma: Src family kinases as central regulators of disease progression.

Multiple myeloma is a malignant condition that most commonly occurs in the seventh decade of life. Recent improvements in treatment may result in a more favourable outlook for recently diagnosed patients. Multiple myeloma is an incurable clonal B-cell malignancy, which is initially responsive to conventional chemotherapy; one-third of the patients achieve complete remission but multidrug resistance eventually develops. Although autologous stem cell transplantation remains an important option, many older patients are less tolerant to the toxicity associated with conditioning treatment, as well as being intrinsically less likely to do well after transplantation. Most patients eventually relapse with or without transplantation, and salvage therapy is only moderately effective. Thalidomide and subsequently, lenalidomide and bortezomib, have demonstrated improved outcomes for these patients, as well as proving efficacious in front-line regimens. A deeper understanding of the molecular mechanisms underlying multiple myeloma has given rise to novel targeted approaches. This review will focus in particular on Src-dependent signalling pathways, reflecting the expanding realisation of the critical and ubiquitous role of Src family kinases (SFKs) in normal and abnormal hematopoiesis.