Table 3.
Examples of preclinical models of CNS metastasis used to examine the efficacy of chemotherapeutic approaches. ACNU, (1-4-amino-2-methyl-5-pyrimidinyl)-methyl-3-(2-chloroethyl)-3-nitrosourea hydrochloride; CCNU, 1-(2-chloroethyl)-3-cyclohexyl-1-nitrosourea; CTX, cyclophosphamide; MTX, methotrexate.
Model | Agent | Effect | Ref. |
---|---|---|---|
MDA-MB-435 melanoma and patient-derived Lu7187 and Lu7466 NSCLC intracranial implant | Sagopilone (ZK-EPO) | Significant inhibition of intracranial tumors | [74] |
MDA-MB-231 breast cancer intracranial implant | Vorinostat + irradiation | Combination with radiation resulted in increased median survival | [75] |
MDA-MB231 (231-Br) breast cancer intracardiac injection | Angiopep-2 paclitaxel conjugate (ANG1005) | Improved delivery into intracranial tumors | [76] |
EMT6 breast cancer intracranial implant | BCNU in combination with biodegradable polymers | Significant prolongation of survival | [77] |
B16 melanoma intracranial implant | Poly(ADP-ribose)glycohydrolase inhibitor GPI16552 + temozolomide | Reduced intracaranial tumor growth and prolonged survival | [78] |
DU145/RasB1 prostate adenocarcinoma intracardiac injection | VEGFR2 RTKI (AZD2171) | Decreased brain metastases vascular bed | [79] |
E0771breast cancer intracranial implant | Interleukin-2 secreting fibroblasts | Significant prolongation of survival | [80] |
MDA-MB231 (231-Br) breast cancer intracardiac injection | vorinostat | Prevents formation of brain metastases | [9] |
Various tumor types intracranial implant | Campothecin analogues | Inhibit growth of melanoma and NSCLC | [81] |
MCF-7/HER2-18 breast cancer intracranial implant | Herceptin | Intracerebral microinfusion of Herceptin increases median survival | [82] |
Walker 256 carcinosarcoma intracardiac injection and intracranial implant | ACNU, CCNU, CTX, MTX | ACNU, CCNU and CTX increases median survival in intracranial implant, all increase median survival in intracardiac model | [83] |
B16 melanoma intracranial implant | IFN-alpha immunotherapy + STAT-3 inhibitor (WP1193) | Significant increase in median survival by combination | [24] |
MDA-MB-231-BR (231-BR-HER2) intracardiac | lapatinib | Decrease in number of large cerebral metastases | [23] |
MDA-MB-468 and Nt2.5luc breast cancer intracranial | Clostridium perfringens enterotoxin | Increased median survival | [84] |