Molecular evolution of central nervous system metastasis and therapeutic implications.

The increasing prevalence and poor prognosis of central nervous system (CNS) metastases pose a significant challenge in oncology, necessitating improved therapeutic strategies. Recent research has shed light on the complex genomic landscape of brain metastases, identifying unique and potentially actionable genetic alterations. These insights offer new avenues for targeted therapy, highlighting the potential of precision medicine approaches in treating CNS metastases. However, translating these discoveries into clinical practice requires overcoming challenges such as availability of tissue for characterization, access to molecular testing, drug delivery across the blood-brain barrier (BBB) and addressing intra- and intertumoral genetic heterogeneity. This review explores novel insights into the evolution of CNS metastases, the molecular mechanisms underlying their development, and implications for therapeutic interventions.

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Declaration of interests P.K.B. has consulted for Angiochem, Merck, Genentech-Roche, Lilly, Tesaro, ElevateBio, Dantari, Atavistik, Voyager Therapeutics, SK Life Sciences, Pfizer, ACI, Sintetica, Kazia, MPM, CraniUS, Axiom and InCephalo, serves on the Scientific Advisory Board for Kazia, has received grant/research support (to MGH) from Merck, Lilly, Mirati, BMS and Kinnate, and speaker’s honoraria from Merck, Genentech-Roche, Lilly and Medscape.