Understanding Brain Metastasis: From Molecular Mechanisms to Treatment Advances
DOI:
https://doi.org/10.56147/jbhs.3.1.122Keywords:
- Brain metastasis,
- Diagnostic imaging,
- Treatment strategies,
- Therapeutic interventions
Abstract
Brain cancer metastasis is one of the most common neurological complications associated with various types of cancer, particularly lung cancer, breast cancer and melanoma. Approximately 20% of cancer patients develop brain metastasis. Current therapeutic strategies are limited and often lack effectiveness, with patient survival typically averaging less than 15 months. As a result, brain metastasis remains one of the leading causes of cancer-related mortality worldwide. Therefore, understanding the mechanisms behind brain metastasis is crucial for improving treatment outcomes. In this review, we provide an overview of the epidemiology, mechanisms, diagnostic approaches, prognostic factors and treatment strategies associated with brain cancer.
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References
Nayak L, Lee EQ, Wen PY (2012) Epidemiology of brain metastases. Curr Oncol Rep 14: 48-54.
Achrol AS, Rennert RC anders C, Soffietti R, Ahluwalia MS, et al. (2019) Brain metastases. Nat Rev Dis Primers 5: 5.
Sperduto PW, Mesko S, Li J, Cagney D, Aizer A, et al. (2020) Survival in patients with brain metastases: Summary report on the updated diagnosis‑specific graded prognostic assessment and definition of the eligibility quotient. J Clin Oncol 38: 3773-3784.
Singh R, Stoltzfus KC, Chen H, Louie AV, Lehrer EJ, et al. (2020) Epidemiology of synchronous brain metastases. JAMA Netw Open 3: e200022.
Bustamante E, Casas F, Luque R, Piedra L, Barros-Sevillano S, et al. (2024) Brain metastasis in triple-negative breast cancer. Breast J: 8816102.
Bertolini F, Spallanzani A, Fontana A, Depenni R, Luppi G (2015) Brain metastases: An overview. CNS Oncol 4: 37-46.
Fox BD, Cheung VJ, Patel AJ, Suki D, Rao G (2011) Epidemiology of metastatic brain tumors. Neurosurg Clin N Am 22: 1-6.
Gray JJ, Moughon SE, Kortemme T, Schueler‑Furman O, Misura KMS, et al. (2003) Protein–protein docking predictions for the CAPRI experiment. Proteins 52: 118-122.
Luissint AC, Artus C, Glacial F, Ganeshamoorthy K, Couraud PO (2012) Tight junctions at the blood brain barrier: Physiological architecture and disease‑associated dysregulation. Fluids Barriers CNS 9: 23.
Wilhelm I, Molnár J, Fazakas C, et al. (2013) Role of the blood-brain barrier in the formation of brain metastases. Int J Mol Sci 14: 1383-1411.
Shumakovich MA, Mencio CP, Siglin JS, Moriarty RA, Geller HM, et al. (2017) Astrocytes from the brain microenvironment alter migration and morphology of metastatic breast cancer cells. FASEB J 31: 5049-5067.
Klein A, Schwartz H, Sagi‑Assif O, Meshel T, Izraely S, et al. (2015) Astrocytes facilitate melanoma brain metastasis via secretion of IL‑23. J Pathol 236: 116-27.
Kerbel RS (2008) Tumor angiogenesis. N Engl J Med 358: 2039-2049.
Zou Y, Watters A, Cheng N, Perry CE, Xu K, et al. (2019) Polyunsaturated fatty acids from astrocytes activate PPARγ signaling in cancer cells to promote brain metastasis. Cancer Discov 9: 1720-1735.
Leibold AT, Monaco GN, Dey M (2019) The role of the immune system in brain metastasis. Curr Neurobiol 10: 33-48.
Lin X, DeAngelis LM (2015) Treatment of brain metastases. J Clin Oncol 33: 3475-3484.
Jung WS, Park CH, Hong C‑K, Suh SH, Ahn SJ (2018) Diffusion‑weighted imaging of brain metastasis from lung cancer: Correlation of MRI parameters with the histologic type and gene mutation status. AJNR Am J Neuroradiol 39: 273-279.
Kerkhof M, Ganeff I, Wiggenraad RGJ, Lycklama À Nijeholt GJ, Hammer S, et al. (2018) Clinical applicability of and changes in perfusion MR imaging in brain metastases after stereotactic radiotherapy. J Neurooncol 138: 133-139.
Horská A, Barker PB (2010) Imaging of brain tumors: MR spectroscopy and metabolic imaging. Neuroimaging Clin N Am 20: 293-310.
Chaung Z, Barnett GC, Knox SJ, Fillipi C, Fine HA, et al. (2021) Limited brain metastases: A narrative review. Ann Palliat Med 10: 5850-5866.
Sperduto PW, Berkey B, Gaspar LE, Mehta M, Curran W (2008) A new prognostic index and comparison to three other indices for patients with brain metastases: An analysis of 1,960 patients in the RTOG database. Int J Radiat Oncol Biol Phys 70: 510-514.
Gaspar L, Scott C, Rotman M, Asbell S, Phillips T, et al. (1997) Recursive Partitioning Analysis (RPA) of prognostic factors in three Radiation Therapy Oncology Group (RTOG) brain metastases trials. Int J Radiat Oncol Biol Phys 37: 745-751.
Gupta S, Singh S, Chophy A, Nair S, Ahuja R, et al. (2022) Analysis of prognostic factors in patients with brain metastases affecting survival. J Egypt Natl Canc Inst 34: 45.
Gaspar LE, Scott C, Murray K, Curran W (2000) Validation of the RTOG Recursive Partitioning Analysis (RPA) classification for brain metastases. Int J Radiat Oncol Biol Phys 47: 1001-1006.
Bipath P, Stopforth LW, Naicker S, Govender P, Sibanda W, et al. (2021) Establishing the utility of recursive partitioning analysis for patients with intra‑cranial metastases managed in a KwaZulu‑Natal state sector Oncology unit. S Afr J Oncol 5: a175.
Brenner AW, Patel AJ (2022) Review of current principles of the diagnosis and management of brain metastases. Front Oncol 12: 857622.
Vogelbaum MA, Brown PD, Messersmith H, Brastianos PK, Burri S, et al. (2022) Treatment for brain metastases: ASCO‑SNO‑ASTRO guideline. J Clin Oncol 40: 492-516.
Rubino S, Oliver DE, Tran ND, Vogelbaum MA, Forsyth PA, et al. (2022) Improving brain metastases outcomes through therapeutic synergy between stereotactic radiosurgery and targeted cancer therapies. Front Oncol 12: 854402.
Bailleux C, Eberst L, Bachelot T (2021) Treatment strategies for breast cancer brain metastases. Br J Cancer 124: 142-155.
Fecci PE, Champion CD, Hoj J, McKernan CM, Goodwin CR, et al. (2019) The evolving modern management of brain metastasis. Clin Cancer Res 25: 6570-6580.
Owonikoko TK, Arbiser J, Zelnak A, Shu HK, Shim H, et al. (2014) Current approaches to the treatment of metastatic brain tumours. Nat Rev Clin Oncol 11: 203-22.
Badiyan SN, Regine WF, Mehta M (2016) Stereotactic radiosurgery for treatment of brain metastases. J Oncol Pract 12: 703-712.
Oliveira FD, Macedo‑Pereira A, Lima J, Sarmento B (2022) Exosomes and brain metastases: A review on their role and potential applications. Int J Mol Sci 22: 10899.
Ene CI, Ferguson SD (2022) Surgical management of brain metastasis: Challenges and nuances. Front Oncol 12: 847110.
Sarmey N, Kaisman‑Elbaz T, Mohammadi AM (2022) Management strategies for large brain metastases. Front Oncol 12: 827304.
Salehi A, Kamath AA, Leuthardt EC, Kim AH (2018) Management of intracranial metastatic disease with laser interstitial thermal therapy. Front Oncol 8: 499.
Rappaport J, Malka J, Khatib A, Amir M, Ganor O, et al. (2019) Management of melanoma brain metastases in the era of immunotherapy and targeted therapy. Melanoma Res 29: 614-622.
Ye L, Wu Y, Zhou J, et al. (2023) Influence of exosomes on astrocytes in the pre-metastatic niche of lung cancer brain metastases. Biol Proced Online 25: 5.
Oliveira FD, Castanho MARB, Neves V, et al. (2021) Exosomes and brain metastases: A review on their role and potential applications. Int J Mol Sci 22: 10899.
Zhou T, Yan Y, Lin M, Zeng C, Mao X, et al. (2025) Astrocyte involvement in brain metastasis: From biological mechanisms to therapeutic strategies. Cancer Metastasis Rev 44: 60.
Li S, Shen Y, Dong C, Yin S, Zhou D, et al. (2023) The molecular and immune microenvironmental landscape of brain metastases: Implications for novel treatment options.
Strickland MR, Alvarez-Breckenridge C, Gainor JF, Brastianos PK (2022) Tumor immune microenvironment of brain metastases: Toward unlocking antitumor immunity. Cancer Discovery 12: 1199-1216.
Neagu MR, Gill CM, Batchelor TT, Brastianos PK (2015) Genomic profiling of brain metastases: Current knowledge and new frontiers. Chin Clin Oncol 4.
Han CH, Brastianos PK (2017) Genetic characterization of brain metastases in the era of targeted therapy. Front Oncol 7: 230.
