Patient-derived tumor organoid predicts drugs response in glioblastoma: A step forward in personalized cancer therapy?

Rapid Processing and Drug Evaluation in Glioblastoma Patient-Derived Organoid Models with 4D Bioprinted Arrays

“…Also, PDOs from gastrointestinal cancers could recapitulate patient responses in clinical trials of personalized medicine (Vlachogiannis et al, 2018). Our studies utilizing GBM-PDOs revealed that niraparib (targeting DDR) and BEZ235 (targeting PI3K/mTOR) could act synergistically, whereas BEZ235 may protect from TMZ toxicity, therefore substantiating another recent report on utilizing PDOs for initiating PI3K/mTOR-targeting therapy in a patient with GBM (Loong et al, 2020) and providing new inroads for combination therapy. Further validations of the synergistic effects in vivo, tailoring combinations against clonal cell subpopulations for each GBM, and including other combinations, e.g., with immune checkpoint inhibitors could support future clinical translation.…”

“…Intriguingly, we identified synergistic activities at lower-than-expected growth inhibitory drug concentrations, therefore suggesting that our 4D printing approach provides a platform to identify potential thresholds for combination therapy to spare the dose-limiting toxicities in GBM ( Mehta et al., 2015 ). In addition, our platform incorporated the assessment of on-target activity offering a validation strategy for personalized therapy ( Bartucci et al., 2016 ; Loong et al., 2020 ; Vlachogiannis et al., 2018 ). We generated a 4D platform using SMP that self-transforms from 3D arrays, for PDO culture, into histological cassettes for rapid assessment of drug sensitivity, on-target activity, and synergy.…”

“…In addition, our platform incorporated the assessment of on-target activity offering a validation strategy for personalized therapy (Bartucci et al, 2016;Loong et al, 2020;Vlachogiannis et al, 2018). We generated a 4D platform using SMP that self-transforms from 3D arrays, for PDO culture, into histological cassettes for rapid assessment of drug sensitivity, on-target activity, and synergy.…”

“…Remarkably, the powerful potential of PDOs in modeling treatment responses and predicting clinical outcome of patients enrolled in clinical trials has been noted ( Vlachogiannis et al., 2018 ). Moreover, a recent case report demonstrated the potential of using PDOs for tailoring treatment in GBM ( Loong et al., 2020 ). Yet, the generation of PDOs for drug testing is still laborious and lengthy, requiring multiple steps including establishing and transporting of PDCs and ECM between thousands of wells for dissociation; making PDOs; allowing cellular growth for weeks to months; performing drug treatment with multiple compounds; assessing cell viability and tumorigenic assays; cell fixation and antibody staining; histologic processing; and final immunohistochemical (IHC) validations.…”

Patient-Derived Cancer Organoids as Predictors of Treatment Response

“…As a proof-of-concept, organoids from one GBM patient, progressive after standard-of-care treatment, was used to identify potential drug candidates based on genomic alterations. This identified everolimus to be a potential therapeutic agent which correlated with a partial clinical response in this case-study (55). Cancer organoids derived from GBM patients were also used to test drug sensitivity to both standard-of-care chemotherapy (temozolomide) and molecular targeted agents towards mTOR, PI3K or DNA damage response.…”