Deconstructing the Biology of Local Relapse Post-Surgery to Develop Novel Preventive Strategies in Brain Metastasis

ASPIRE Award (2021-2023)

Manuel Valiente, DVM, PhD, Centro Nacional de Investigaciones Oncológicas (CNIO) (Spain)

Manuel Valiente, DVM, PhD

Approximately 10-20% of individuals with cancer will eventually develop brain metastases, with poor prognostic outcome. Current therapeutic options are only temporarily effective, mostly due to an inability to remove all cancer cells from the brain, leading to relapse. Despite a high unmet need for improved treatments, metastatic brain cancer is understudied due to its complex biology and lack of experimental model systems.

Manuel Valiente and his team have developed a first-of-its-kind mouse model of full local relapse post-neurosurgery. Their preliminary data reveals that invasive fronts of tumors are closely associated with pre-existing blood vessels in the brain, indicating that this microenvironment may promote resurgence of tumor cells. Now they plan to characterize the process of local relapse after neurosurgery for the first time. Using their novel mouse model as well as human clinical samples, and applying the analytical techniques of spatial transcriptomics and immunofluorescence, Valiente’s team will establish a map of relapse at the molecular and single cell level by examining the cancer cells and their surrounding microenvironment in a time-lapse manner. They will also functionally test a previously discovered gene signature that differentiates relapsed metastases from their matched surgically resected counterparts. These studies will significantly accelerate efforts to functionally characterize the molecular changes which occur during local relapse. Findings from this project will lay the groundwork for further research towards developing new therapeutic options for patients with brain metastasis.

published research

Zhu L, Miarka L, Baena P, Perea-García M, Valiente M. Protocol to generate murine organotypic brain cultures for drug screening and evaluation of anti-metastatic efficacy. STAR Protoc. 2023.

Valiente M, Ortega-Paino E. Updating cancer research with patient-focused networks. Trends Cancer. 2023.