An international team of researchers, led by the Spaniard José Ángel Martínez-Climent from the Cima University of Navarra, has created mouse avatars of multiple myeloma patients to study and develop personalized treatments against this blood cancer, the second most common blood cancer and incurable in most cases.
Artificial mice carry a replica of a patient’s tumor and have the ability to mimic the genetic and immunological diversity of the origin and evolution of this disease. This advance, published in the prestigious magazine nature medicine will allow researchers to design more effective and personalized therapies for multiple myeloma.
The results of the work open a path of investigation that could expand to other hematological and solid tumors to find effective treatments for patients who currently have no healing options.
He 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.
To meet the medical need for new treatments to cure the disease, 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.
Thanks to 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 Cima’s Hemato-Oncology Program and first author of the study.
What does this finding mean for patients with multiple myeloma?
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, also belonging to Cima’s Hemato-Oncology Program.
This research will allow researchers anticipate treatment outcome with next-generation immunotherapies and mimic in the laboratory clinical situations associated with the worst results, such as high-risk multiple myeloma, extramedullary disease or acquired therapeutic resistance. “This scenario offers us opportunities to advance in the investigation of new therapeutic strategies and to optimize the design of future immunotherapy clinical trials,” says Martínez-Climent.
“We are testing novel therapies in experimental models”
Besides, “we are testing novel therapies in experimental models at stages of the disease where multiple myeloma cells might be more vulnerable, particularly in early precursor conditions or in the minimal residual disease state (after treatment, when few tumor cells remain). To do this, we have established numerous scientific collaborations with pharmaceutical companies that are developing clinical trials in this disease to do these same tests in our mice.”
The ultimate goal, the researchers note, “is to transferring discoveries from the laboratory to the clinic and that research initiatives like ours can be extrapolated to other hematologic malignancies and solid tumors that remain incurable with currently available treatments.”
Hospitals, research centers, biotechnology and pharmaceutical companies from Spain, Switzerland, the United States and Japan. The leading researchers of the project are integrated into the Cancer Center Clínica Universidad de Navarra and belong to the Cancer Network Biomedical Research Center (CIBERONC) and the Health Research Institute of Navarra (IdiSNA).
The research has been funded by the imCORE Network, from the Ministry of Health, the Ministry of Science and Innovation, from the Carlos III Health Institute (co-financed with FEDER funds), from the Paula and Rodger Riney Foundation and the Roberto Arnal Planelles Foundation. In turn, it has also had the support of other public and private institutions, such as Iberdrola, through the Spanish Association Against Cancer within its call for “Accelerator Grants” (EDITOR Project).
Institutions participating in the study:
Spain: Cancer Center Clínica Universidad de Navarra, Severo Ochoa Molecular Biology Center, National Cancer Research Center, Navarrabiomed.
Switzerland: Innovation Center of the pharmaceutical company Roche.
Japan: University of Tsukuba.
United States: Mayo Clinic, Yale University, Dana-Farber Cancer Institute at Harvard University, Cornell University, and the biotech company Genentech.
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