Genetics of multiple myeloma revealed
The 'Novel therapeutic antibodies for multiple myeloma' (MMSC) project aimed to identify candidate oncogenes, genes that can cause cancer, by screening for activity of their proteins. Two genes have been isolated using small hairpin (sh) RNA based screening tools. shRNA molecules can be used to silence target genes and thus assess their function. The proteins from the translated genes can be targeted using monoclonal antibodies or small molecules, many of which are already used in chemotherapy. An attractive candidate, the first gene is part of the Wingless (WNT) pathway, first recognised for its role in carcinogenesis. Mutations of WNT are critical in breast and prostate cancer. This protein is also a receptor tyrosine kinase (RTK). RTKs are often overexpressed in a variety of tumours, leading to enhanced cancer cell survival, and metastasis. Several RTKs are expressed in MM and there is mounting evidence of their relevance in this disease. RTK-targeting therapeutic antibodies and small molecule inhibitors such as Herceptin, Cetuximab, Gleevec, Tarceva and Iressa have successfully induced death in cancerous cells where RTKs are overexpressed. The second gene is also a kinase and part of the Hippo pathway. Inhibition of this kinase using shRNAs was able to trigger cell death in a large range of myeloma cells. Downregulation of this gene in an in vivo setting confirmed that it could be used to unravel mechanisms of cancer cell survival. The results of the MMSC project have provided a firm knowledge platform for the development of targeted drug therapies for MM. Besides advanced research opportunities for pharmaceutical SMEs, MM patients also stand to benefit from improved life quality and outcome.
Keywords
Multiple myeloma, cancer, antibodies, oncogene, small hairpin RNA, Wingless, receptor tyrosine kinase, targeted drug therapy
