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Overcoming clinical relapse in multiple myeloma by understanding and targeting the molecular causes of drug resistance

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Multiple myeloma and drug resistance

Multiple myeloma (MM) is a cancer of white blood cells normally responsible for producing antibodies. European scientists addressed the urgent need for a strategy to overcome drug resistance in MM treatment.


MM is considerate to be an incurable but treatable cancer. The overall survival of intensively treated patients below 65-70 years of age is 8-9 years and event-free survival is 3-4 years. Despite recent advances in the treatment of MM, patients invariably become resistant to treatment and succumb to their disease. Limited knowledge of the mechanisms of relapse and resistance in MM is the main obstacle in designing innovative treatment strategies. The EU-funded OVER-MYR (Overcoming clinical relapse in multiple myeloma by understanding and targeting the molecular causes of drug resistance) three-year project worked to develop a strategy to uncover mechanisms of MM resistance to treatment. Researchers focused on the impact of the tumour microenvironment in developing drug resistance and on understanding the mechanisms of resistance in MM cells to existing drugs. In the first 18 months, the 9 members of the international consortium worked on the recruitment and analysis of all patient data, the generation of drug-resistant cell lines and in vivo (murine) models to identify resistance mechanisms. The focus was on fibroblasts, endothelial cells, osteoblasts, osteoclasts and different types of immune cells. Results obtained clearly demonstrated that the bone marrow microenvironment supported proliferation of the myeloma cells and protected them against drugs that are currently used for the treatment. Researchers generated a panel of drug resistant myeloma cells for comparison against the parental lines. They discovered several gene mutations that impacted gene expression and protein functions. The identified targets were used for screening the library of compounds for activity against drug resistance in myeloma cells. Several potential leads were identified that had synergistic activity with the current drugs, proving the clinical application of new combinations. In conclusion, OVER-MYR resulted in a significant amount of new basic data about mechanisms of drug resistance in the course of MM treatment. The knowledge has been disseminated by the partners through conference presentations, press releases and more than 50 publications in peer-reviewed journals.


Multiple myeloma, drug resistance, cancer, OVER-MYR, tumour, gene mutations

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