Targeting adhesion molecules in myeloma – (Podar et al, BJH Nov-II, 2011)
There is increasing interest in the therapeutic potential of targeting adhesion molecules in myeloma. Strategies include targeting surface antigen adhesion molecules including integrins, cadherins, immunoglobulin like cell adhesion molecules, selectins and CD44 and their relative down-stream signalling pathways. Adhesion molecules mediate cell to cell adhesion and cell adhesion to various components of the extra-cellular matrix. It is hypothesized that disruption of adhesion using so-called selective adhesion molecule (SAM) inhibitors will prevent ‘cancer defining processes’ including adhesion initiated signalling cascades, tumour cell proliferation, survival, homing, migration, metastases and cell adhesion mediated drug resistance.
Podar et al (BJH Nov-II, 2011) recently report some promising results using Natalizumab, a recombinant humanised monoclonal antibody directed against the cellular adhesion molecule α4, a sub-unit of VLA-4. They successfully demonstrate the ability of Natalizumab to prevent adhesion of myeloma cells to cellular and non-cellular components of the bone marrow micro-environment, reduced proliferation of myeloma cells, reduced angiogenesis and increased chemo-sensitivity, (albeit in an in vitro ‘therapeutically representative human co-culture system’) of myeloma cells to Bortezomib. Proven efficacy in clinical trials is required but this interesting indirect approach may well have substantial therapeutic potential. Expect more focus on adhesion molecules in myeloma!