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FP7 OPTATIO project researches new strategies to fight against multiple myeloma

A villain on his own doesn’t do much damage. It’s only when he has a few loyal companions around him which serve and protect him that he becomes powerful and dangerous.

This is also true for multiple myeloma, a bone marrow based type of blood cancer. Researchers have to date focused on therapy aimed primarily at the cancer cells. Recently however scientists have realized that not enough attention was being paid to the impact of the bone marrow microenvironment on the disease. The microenvironment, healthy cells “abused” by the cancer, often provide a protective niche for the tumor and in many cases optimal conditions for growth. The concept of the OPTATIO project is to develop tools to interfere with the cancer microenvironment and in this way improve the chances of therapy in the fight against multiple myeloma.

OPTATIO (OPtimizing TArgets and Therapeutics In high risk and refractOry Multiple Myeloma) is an EU project under Framework Programme 7 and brings together the expertise from twelve partner institutions from Austria, Germany, the Czech Republic, Italy, Hungary, and Spain. The scientific coordinator is Dr. Wolfgang Willenbacher from Innsbruck Medical University.

Two thirds of Multiple Myeloma develops in older patients (average age at diagnosis is 69 years) and is nearly always incurable. It is a tumor of the immune system, developing from mature antibody producing B cells. The start is a single degenerative cell which multiplies on a massive scale and infiltrates through the bone marrow and beyond. This affects the development of blood cells in the bone marrow and often severely damages the skeleton. The patient becomes anemic and succumbs easily to infections. In addition myeloma cells often produce large amounts of “toxic” antibodies and antibody fragments leading to problems in kidney function and may lead to acute renal failure. In Europe and the USA 50,000 people per year are diagnosed with multiple myeloma.

 

Microenvironment boosts resistance

Multiple myeloma cells grow in niches in the bone marrow. They are surrounded by tissue cells, bone marrow cells (osteoblasts and osteoclasts), blood vessel cells and immune cells. These cells stimulate each other in a highly interactive way by close contact and soluble factors. There is a regular interplay and exchange of messenger substances, e.g. cytokines. Genes are activated so that even more cytokines are produced and a self strengthening cycle exists. This assists in helping cancer cells to “hide” and avoid cell death which should normally be the result of medication. The explanation of this resistance mechanism is one of the aims of OPTATIO.

A further aim of OPTATIO is to investigate whether the microenvironment is responsible for the fact that this cancer develops from an obligatory precursor stage called “Monoclonal gammopathy of unknown significance” (MGUS), which is often identified in the older generation (up to 3% of people over 60 years old) and is mostly harmless. However in 1% of cases per year, this precursor stage develops into frank Multiple Myeloma. The deciding factors for progression into Multiple Myeloma are not yet well understood. This will also be investigated within OPTATIO.

The project has assembled an international scientific collaborative consortium, combining the expertise of academic, clinical, SMEs and industrial partners to achieve the project's objectives.