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Summary: While bortezomib has significant benefits in multiple myeloma (MM) therapy, the disease remains incurable due to the invariable development of bortezomib resistance. This emphasises the need for advanced models for preclinical evaluation of new therapeutic approaches for bortezomib‐resistant MM. Here, we describe the development of an orthotopic syngeneic bortezomib‐resistant MM mouse model based on the most well‐characterised syngeneic MM mouse model derived from spontaneous MM‐forming C57BL/KaLwRij mice. Using bortezomib‐resistant 5TGM1 cells, we report and characterise a robust syngeneic mouse model of bortezomib‐resistant MM that is well suited to the evaluation of new therapeutic approaches for proteasome inhibitor‐resistant MM. [ABSTRACT FROM AUTHOR]

Glioblastoma is one of the most common and lethal types of primary brain tumor. Despite aggressive treatment with chemotherapy and radiotherapy, tumor recurrence within 6–9 months is common. To overcome this, more effective therapies targeting cancer cell stemness, invasion, metabolism, cell death resistance and the interactions of tumor cells with their surrounding microenvironment are required. In this study, we performed a systematic review of the molecular mechanisms that drive glioblastoma progression, which led to the identification of 65 drugs/inhibitors that we screened for their efficacy to kill patient-derived glioma stem cells in two dimensional (2D) cultures and patient-derived three dimensional (3D) glioblastoma explant organoids (GBOs). From the screening, we found a group of drugs that presented different selectivity on different patient-derived in vitro models. Moreover, we found that Costunolide, a TERT inhibitor, was effective in reducing the cell viability in vitro of both primary tumor models as well as tumor models pre-treated with chemotherapy and radiotherapy. These results present a novel workflow for screening a relatively large groups of drugs, whose results could lead to the identification of more personalized and effective treatment for recurrent glioblastoma. [ABSTRACT FROM AUTHOR]