Melanoma Brain Metastasis: Mechanisms, Models, and Medicine
Abstract
:1. Tumor Cell Metastasis
2. Mechanisms of Melanoma Brain Metastasis
2.1. Melanoma Cell Arrest within the Brain Microvasculature
2.2. Extravasation
2.3. Perivascular Positioning and Growth by Vessel Co-Option
3. AKT Signaling and Melanoma Brain Metastasis
4. Animal Models of Melanoma Brain Metastasis
5. Melanoma Brain Metastasis Therapies
5.1. Surgery
5.2. Stereotactic Radiosurgery
5.3. Whole-Brain Radiation Therapy
5.4. Chemotherapy
5.5. Targeted Therapies
5.6. MAPK Pathway Inhibitors
5.7. Immune-Based Therapies
6. Conclusions
Acknowledgments
Author Contributions
Conflicts of Interest
References
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Trial | Phase | Status | Primary Outcome Measured | Title |
---|---|---|---|---|
NCT01721603 | II | Active, not recruiting | Safety/efficacy | A Phase 2 Prospective Trial of Dabrafenib with Stereotactic Radiosurgery in BRAFV600E Melanoma Brain Metastases |
NCT02115139 | II | Recruiting | 1-year survival rate | GEM STUDY: Radiation and Yervoy in Patients with Melanoma and Brain Metastases (GRAY-B) |
NCT01703507 | I | Active, not recruiting | Maximum tolerated dose ipilimumab | Phase I Study of Ipilimumab Combined with Whole Brain Radiation Therapy or Radiosurgery for Melanoma |
NCT02085070 | II | Recruiting | Response rate | MK-3475 in Melanoma and NSCLC Patients with Brain Metastases |
NCT02097732 | II | Recruiting | Local control rate | Ipilimumab Induction in Patients with Melanoma Brain Metastases Receiving Stereotactic Radiosurgery |
NCT02039947 | II | Recruiting | Intracranial response rate | Study to Evaluate Treatment of Dabrafenib Plus Trametinib in Subjects with BRAF Mutation-Positive Melanoma That Has Metastasized to the Brain |
NCT01378975 | II | Completed, no posts | Best overall response rate | A Study of Vemurafenib in Metastatic Melanoma Patients with Brain Metastases |
NCT01978236 | II | Recruiting | Concentrations of dabrafenib & trametinib in metastases | Dabrafenib/Trametinib, BRAF or BRAF AND MEK Pre-op with BRAF and MEK Post-op, Phase IIB, Melanoma with Brain Mets, Biomarkers and Metabolites |
NCT02320058 | II | Recruiting | Clinical benefit rate | A Multi-Center Phase 2 Open-Label Study to Evaluate Safety and Efficacy in Subjects with Melanoma Metastatic to the Brain Treated with Nivolumab in Combination with Ipilimumab Followed by Nivolumab Monotherapy (CheckMate 204) |
NCT01503827 | III | Recruiting | Distant intracranial failure | Whole Brain Radiotherapy Following Local Treatment of Intracranial Metastases of Melanoma (WBRTMel) |
NCT01644591 | III | Active, not recruiting | Time to local failure | Trial to Compare Local Control and Neurocognitive Preservation after Initial Treatment with Stereotactic Radiosurgery (SRS) versus Whole Brain Radiation Therapy (WBRT) for Patients with >3 Brain Metastases from Melanoma |
NCT02460068 | III | Recruiting | Overall survival rate | A Study of Fotemustine(FTM) vs. FTM and Ipilimumab (IPI) or IPI and Nivolumab in Melanoma Brain Metastasis (NIBIT-M2) |
NCT02374242 | II | Recruiting | Intracranial response rate | Anti-PD 1 Brain Collaboration for Patients with Melanoma Brain Metastases (ABC) |
NCT02662725 | II | Completed, no posts | Overall survival rate | Ipilimumab Combined with a Stereotactic Radiosurgery in Melanoma Patients with Brain Metastases (IPI + RTS) |
NCT02308020 | II | Recruiting | Complete response, partial response, objective intracranial response rates | A Study of Abemaciclib (LY2835219) in Participants with Breast Cancer, Non-small Cell Lung Cancer, or Melanoma That Has Spread to the Brain |
NCT02681549 | II | Recruiting | Brain metastasis response rate | Pembrolizumab Plus Bevacizumab for Treatment of Brain Metastases in Metastatic Melanoma or Non-small Cell Lung Cancer |
NCT02621515 | II | Recruiting | Best overall response rate | Nivolumab in Symptomatic Brain Metastases (CA209-322) |
NCT02716948 | I | Recruiting | Incidence of serious adverse events | Stereotactic Radiosurgery and Nivolumab in Treating Patients with Newly Diagnosed Melanoma Metastases in the Brain or Spine |
NCT01904123 | I | Not yet recruiting | Maximum tolerated dose WP1066 | A Phase I Trial of WP1066 in Patients with Central Nervous System (CNS) Melanoma and Recurrent Glioblastoma Multiforme (GBM) |
NCT02452294 | II | Recruting | Intracranial disease control rate | Buparlisib in Melanoma Patients Suffering from Brain Metastases (BUMPER) |
NCT02537600 | II | Recruiting | Complete or partial intracranial response rate | Vemurafenib and Cobimetinib Combination in BRAF Mutated Melanoma with Brain Metastasis (CONVERCE) |
NCT02107755 | II | Recruiting | Progression-free survival rate | Stereotactic Radiation Therapy and Ipilimumab in Treating Patients with Metastatic Melanoma |
NCT01983124 | II | Completed, no posts | Progression-free survival rate | Vemurafenib + Fotemustine to Treat Advanced Melanoma Patients with V600BRAF Mutation Recurred While on Vemurafenib (BeyPro1) |
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Share and Cite
Kircher, D.A.; Silvis, M.R.; Cho, J.H.; Holmen, S.L. Melanoma Brain Metastasis: Mechanisms, Models, and Medicine. Int. J. Mol. Sci. 2016, 17, 1468. https://doi.org/10.3390/ijms17091468
Kircher DA, Silvis MR, Cho JH, Holmen SL. Melanoma Brain Metastasis: Mechanisms, Models, and Medicine. International Journal of Molecular Sciences. 2016; 17(9):1468. https://doi.org/10.3390/ijms17091468
Chicago/Turabian StyleKircher, David A., Mark R. Silvis, Joseph H. Cho, and Sheri L. Holmen. 2016. "Melanoma Brain Metastasis: Mechanisms, Models, and Medicine" International Journal of Molecular Sciences 17, no. 9: 1468. https://doi.org/10.3390/ijms17091468