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Review
. 2021 May 28;13(11):2645.
doi: 10.3390/cancers13112645.

Molecular Profiles of Brain Metastases: A Focus on Heterogeneity

Shan Ali  1 , Zuzanna Górska  2 , Renata Duchnowska  2 , Jacek Jassem  1
Affiliations
Review

Molecular Profiles of Brain Metastases: A Focus on Heterogeneity

Shan Ali et al. Cancers (Basel). .

Abstract

Brain metastasis is a common and devastating clinical entity. Intratumor heterogeneity in brain metastases poses a crucial challenge to precision medicine. However, advances in next-generation sequencing, new insight into the pathophysiology of driver mutations, and the creation of novel tumor models have allowed us to gain better insight into the genetic landscapes of brain metastases, their temporal evolution, and their response to various treatments. A plethora of genomic studies have identified the heterogeneous clonal landscape of tumors and, at the same time, introduced potential targets for precision medicine. As an example, we present phenotypic alterations in brain metastases originating from three malignancies with the highest brain metastasis frequency: lung cancer, breast cancer, and melanoma. We discuss the barriers to precision medicine, tumor heterogeneity, the significance of blood-based biomarkers in tracking clonal evolution, the phylogenetic relationship between primary and metastatic tumors, blood-brain barrier heterogeneity, and limitations to ongoing research.

Keywords: brain metastases; breast cancer; cancer; genomics; heterogeneity; immunotherapy; lung cancer; melanoma; precision medicine; targeted therapy.

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Conflict of interest statement

J.J. speaker for AstraZeneca, Boehringer Ingelheim, Roche, Pfizer; advisory roles for AstraZeneca, BMS, Pfizer, MSD; travel support from Roche and Pfizer. R.D. speaker for AstraZeneca, Roche, Pfizer, Novartis, Eli Lilly, Amgen; advisory roles for AstraZeneca, Roche, Pfizer, Novartis, Eli Lilly; travel support from Roche, Pfizer, Amgen. The other authors declare no conflicts of interest.

References

    1. Davis F.G., Dolecek T.A., McCarthy B.J., Villano J.L. Toward determining the lifetime occurrence of metastatic brain tumors estimated from 2007 United States cancer incidence data. Neuro. Oncol. 2012;14:1171–1177. doi: 10.1093/neuonc/nos152. - DOI - PMC - PubMed
    1. Gavrilovic I.T., Posner J.B. Brain metastases: Epidemiology and pathophysiology. J. Neurooncol. 2005;75:5–14. doi: 10.1007/s11060-004-8093-6. - DOI - PubMed
    1. Barnholtz-Sloan J.S., Sloan A.E., Davis F.G., Vigneau F.D., Lai P., Sawaya R.E. Incidence proportions of brain metastases in patients diagnosed (1973 to 2001) in the Metropolitan Detroit Cancer Surveillance System. J. Clin. Oncol. 2004;22:2865–2872. doi: 10.1200/JCO.2004.12.149. - DOI - PubMed
    1. Schouten L.J., Rutten J., Huveneers H.A.M., Twijnstra A. Incidence of brain metastases in a cohort of patients with carcinoma of the breast, colon, kidney, and lung and melanoma. Cancer. 2002;94:2698–2705. doi: 10.1002/cncr.10541. - DOI - PubMed
    1. Parsons D.W., Jones S., Zhang X., Lin J.C.H., Leary R.J., Angenendt P., Mankoo P., Carter H., Siu I.M., Gallia G.L., et al. An integrated genomic analysis of human glioblastoma multiforme. Science. 2008;321:1807–1812. doi: 10.1126/science.1164382. - DOI - PMC - PubMed