Ex vivo drug screening on patient-derived tumor material to advance functional precision in oncology: an overview on current approaches and unresolved challenges

The advent of mutation-informed targeted therapies has transformed medical oncology, delivering durable responses in several cancer types. However, this success has not been universal. Tumors such as glioblastoma have largely remained unresponsive to genomics-guided personalized treatments, and in many cancers, the correlation between genetic alterations and therapeutic response remains inconsistent. To address these limitations, functional precision oncology - based on ex vivo drug screening using patient-derived tumor cells - has emerged as a compelling complementary approach. By directly testing drug responses in tumor cells, this strategy seeks to bypass the shortcomings of purely genomic prediction models, particularly in malignancies that have proven refractory to current targeted approaches. This review outlines the state-of-the-art methodologies for patient-derived cell-based drug screening, examining their application across various tumor types and highlighting the current challenges and opportunities in implementing functional precision medicine in clinical oncology.