The first stem cell-derived organoid-based GBM models enabling the study of tumor initiation recurred to genome-editing techniques like the Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR)/CRISPR-associated (Cas) nuclease 9 (CRISPR/Cas9) technology [54,55] to introduce specific genetic alterations that are commonly found in GBM, affecting genes such as EGFR, NF1, TP53, TERT, and CDKN2A/B [14,56] (Table 1). Here, TP53 is linked to neoplasm.