Table 2.

Overview of reviewed studies involving the use of LB100 as monotherapy or combination therapy against tumors of the nervous system. CAIX = Carbonic Anhydrase IX; CAR = Chimeric Antigen Receptor; DIPG = Diffuse Intrinsic Pontine Glioma; FGFR = Fibroblast Growth Factor Receptor; GBM = Glioblastoma; NB = Neuroblastoma; NCoR = Nuclear Receptor Corepressor 1; PHEO = Pheochromocytoma; POD = Postoperative Day; PRMT5 = Protein arginine methyltransferase 5.

Investigators (Year)	Tumor Type	Treatment Method	Outcome
Lu et al. [95] (2010)	Glioblastoma	LB100 only	LB100 inhibited PP2A and caused dose-dependent antiproliferative activity in two GBM cell lines. LB100 treatment resulted in a significant reduction in tumor volume compared to controls (p < 0.001) in vivo. In vivo experiments also resulted in decreased nuclear N-CoR expression.
Gordon et al. [97] (2015)	Glioblastoma	LB100 and radiation therapy	LB100 resulted in radiation dose enhancement and increased mitotic catastrophe. Combination therapy significantly enhanced tumor growth delay while decreasing p53 in vivo. Combination therapy also increased the overall survival of mouse xenografts.
Cui et al. [98] (2020)	Glioblastoma	LB100 and CAR-T cells	Anti-CAIX CAR-T cell and LB100 combination therapy resulted in significant cytotoxicity against GBM tumor cells and increased cytokine production compared to control T-cell treatment in vitro. Combination therapy significantly increased tumor regression compared to monotherapy in vivo (p < 0.05) and significantly prolonged survival (p < 0.001).
Maggio et al. [99] (2020)	Glioblastoma	LB100 and PD-1 inhibition	Combination therapy significantly improved survival compared to monotherapy (p < 0.005) and controls (p < 0.001). Complete tumor regression was seen in 25% of combination-treated mice but no other subgroups.
Otani et al. [100] (2021)	Glioblastoma	LB100 and PRMT5 knockdown	LB100 administration significantly reduced viability in PRMT5-depleted GBMNS compared to PRMT5-intact GBMNS. PRMT5 knockdown and LB100 combination therapy increased the expression of phospho-MLKL. Combination therapy significantly decreased tumor size and prolonged survival in in vivo mouse xenografts.
Lu et al. [94] (2009)	Neuroblastoma and GBM	LB102 and TMZ	LB102 treatment in U87MG GBM cells resulted in morphological features of mitotic catastrophe. LB102 caused complete regression of GBM xenografts with no recurrence in 50% of animals and inhibited the growth of NB xenografts.
Martiniova et al. [101] (2011)	Pheochromocytoma	LB100 and TMZ	Combination therapy resulted in significantly greater tumor cell inhibition in vitro compared to monotherapy. PHEO mouse xenografts treated with combination therapy had significantly prolonged survival compared to monotherapy (p < 0.0001). Combination therapy significantly delayed the appearance of hepatic tumors compared to monotherapy alone (p < 0.0001).
Ho et al. [87] (2016)	Medulloblastoma	LB100 and cisplatin	LB100 alone had a potent antitumor effect of multiple medulloblastoma cell lines. Combination therapy enhanced cisplatin cytotoxicity and significantly decreased medulloblastoma cell viability as compared to controls (p < 0.005). Combination therapy significantly reduced tumor burden on POD64 compared to cisplatin treatment alone (p < 0.05) in vivo.
Schramm et al. [110] (2019)	DIPG	LB100 only	Investigators used a large-scale gene knockdown approach using shRNA and DNA sequencing to identify susceptibilities of DIPG tumor cells. Screening resulted in FGFR and PP2A deemed as candidate targets. LB100 therapy induced apoptosis in two DIPG cell lines in a dose-dependent manner and increased pAkt expression in vitro.