title: Towards Stratified Medicine in Plasma Cell Myeloma.
abstract: Plasma cell myeloma is a clinically heterogeneous malignancy accounting for approximately one to 2% of newly diagnosed cases of cancer worldwide. Treatment options, in addition to long-established cytotoxic drugs, include autologous stem cell transplant, immune modulators, proteasome inhibitors and monoclonal antibodies, plus further targeted therapies currently in clinical trials. Whilst treatment decisions are mostly based on a patient's age, fitness, including the presence of co-morbidities, and tumour burden, significant scope exists for better risk stratification, sub-classification of disease, and predictors of response to specific therapies. Clinical staging, recurring acquired cytogenetic aberrations, and serum biomarkers such as β-2 microglobulin, and free light chains are in widespread use but often fail to predict the disease progression or inform treatment decision making. Recent scientific advances have provided considerable insight into the biology of myeloma. For example, gene expression profiling is already making a contribution to enhanced understanding of the biology of the disease whilst Next Generation Sequencing has revealed great genomic complexity and heterogeneity. Pathways involved in the oncogenesis, proliferation of the tumour and its resistance to apoptosis are being unravelled. Furthermore, knowledge of the tumour cell surface and its interactions with bystander cells and the bone marrow stroma enhance this understanding and provide novel targets for cell and antibody-based therapies. This review will discuss the development in understanding of the biology of the tumour cell and its environment in the bone marrow, the implementation of new therapeutic options contributing to significantly improved outcomes, and the progression towards more personalised medicine in this disorder.
authors: Northern Ireland Centre for Stratified Medicine, Biomedical Sciences Research Institute, Ulster University, C-TRIC Building, Altnagelvin Area Hospital, Glenshane Road, Derry/Londonderry BT47 6SB, Northern Ireland. egan-p2@email.ulster.ac.uk.
authors: Philip
authors: P
authors: Egan
authors: Northern Ireland Centre for Stratified Medicine, Biomedical Sciences Research Institute, Ulster University, C-TRIC Building, Altnagelvin Area Hospital, Glenshane Road, Derry/Londonderry BT47 6SB, Northern Ireland. s.drain@ulster.ac.uk.
authors: Stephen
authors: S
authors: Drain
authors: Northern Ireland Centre for Stratified Medicine, Biomedical Sciences Research Institute, Ulster University, C-TRIC Building, Altnagelvin Area Hospital, Glenshane Road, Derry/Londonderry BT47 6SB, Northern Ireland. c.conway@ulster.ac.uk.
authors: Caroline
authors: C
authors: Conway
authors: Northern Ireland Centre for Stratified Medicine, Biomedical Sciences Research Institute, Ulster University, C-TRIC Building, Altnagelvin Area Hospital, Glenshane Road, Derry/Londonderry BT47 6SB, Northern Ireland. aj.bjourson@ulster.ac.uk.
authors: Anthony J
authors: AJ
authors: Bjourson
authors: Northern Ireland Centre for Stratified Medicine, Biomedical Sciences Research Institute, Ulster University, C-TRIC Building, Altnagelvin Area Hospital, Glenshane Road, Derry/Londonderry BT47 6SB, Northern Ireland. d.alexander@ulster.ac.uk.
authors: H Denis
authors: HD
authors: Alexander
mesh_terms: D014408:Biomarkers, Tumor / Q000235:genetics; D018450:Disease Progression; D015972:Gene Expression Regulation, Neoplastic; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D006801:Humans; D008998:Monoclonal Gammopathy of Undetermined Significance / Q000235:genetics* / Q000473:pathology / Q000628:therapy; D009101:Multiple Myeloma / Q000235:genetics* / Q000473:pathology / Q000628:therapy; D009364:Neoplasm Recurrence, Local; D018365:Neoplasm, Residual / Q000235:genetics / Q000473:pathology; D017063:Outcome Assessment, Health Care
chemical_list: D014408:Biomarkers, Tumor
keywords: Next Generation Sequencing; flow cytometry; immunomodulatory drugs; microRNAs; multiple myeloma; personalised medicine; plasma cell dyscrasias; plasma cell myeloma; proteasome inhibitors