A team of Spanish researchers have created mouse avatars of patients with multiple myeloma to study and develop personalized treatments against this blood cancer, the second most frequent and incurable hematological cancer in most cases. These artificial mice have the ability to mimic the genetic and immunological diversity of the origin and evolution of this disease in patients. This advance, published in “Nature Medicine”, will allow researchers to design more effective and personalized therapies for multiple myeloma.
The results of the study open an avenue of research that could be expanded to other hematologic and solid tumors to find effective treatments for patients who currently have no cure options.
Multiple myeloma is a blood cancer that occurs in the bone marrow.. It occurs due to the proliferation of plasma cells, a type of immune cells responsible for producing antibodies. It is a heterogeneous disease, which means that it can manifest itself in different ways and have different responses to treatments.
Researchers have used genetic engineering technologies and multi-omic analysis at the cellular and molecular level. With this advanced technology, they have been able to characterize more than 500 genetically heterogeneous mice that develop multiple myeloma, and samples from more than 1,000 patients with this disease, treated in the Hematological Cancer Area of the Cancer Center Clínica Universidad de Navarra.
Through this analysis, “we have generated artificial mice that accurately reflect key aspects of the origin and development of human multiple myeloma. This allows us to study the progression of the disease, test therapeutic alternatives and predict the response to combinations of immunotherapeutic drugs in the clinic,” says Marta Larráyoz, researcher at the Hemato-Oncology Program at the Cima University of Navarra and first author of the study.
Advancing work in the laboratory requires being able to compare and validate the information provided by preclinical models with patient data. “Thanks to our ongoing collaboration with the hematologists at the Cancer Center Clínica Universidad de Navarra, we have identified in our mouse models of multiple myeloma a correlation between the genetic and immunological traits of each tumor and its selective response to preclinical therapies,” says José Ángel Martínez-Climent, principal investigator and coordinator of the study.
The authors assure that this research will allow researchers to anticipate the outcome of treatment with next-generation immunotherapies and imitate in the laboratory clinical situations associated with the worst outcomes, such as high-risk multiple myeloma, extramedullary disease, or therapeutic resistance. acquired.
This scenario offers us opportunities to advance in the investigation of new therapeutic strategies and to optimize the design of future clinical trials of immunotherapy,” says Martínez-Climent.
experimental model
In addition, “we are testing novel therapies in experimental models at stages of the disease where multiple myeloma cells might be most vulnerable, particularly in early precursor conditions or in the minimal residual disease state (after treatment, when few cells remain). tumors). To do this, we have established numerous scientific collaborations with pharmaceutical companies that are developing clinical trials in this disease to carry out these same trials in our mice.”
The ultimate goal, the researchers say, “is to transfer the findings from the laboratory to the clinic so that research initiatives such as ours can be extrapolated to other hematological malignancies and solid tumors that remain incurable with currently available treatments.”