see also Intracranial metastases
Despite the frequency of brain metastases, prospective trials in this patient population are limited, and the criteria used to assess response and progression in the CNS are heterogeneous 1).
Whether brain metastases harbor distinct genetic alterations beyond those observed in primary tumors is unknown.
Brastianos et al. detected alterations associated with sensitivity to PI3K/AKT/mTOR, CDK, and HER2/EGFR inhibitors in the brain metastases. Genomic analysis of brain metastases provides an opportunity to identify potentially clinically informative alterations not detected in clinically sampled primary tumors, regional lymph nodes, or extracranial metastases 4).
CDH2, KIFC1, and FALZ3
The management of patients with brain metastases has become a major issue due to the increasing frequency and complexity of the diagnostic and therapeutic approaches. In 2014, the European Association of NeuroOncology (EANO) created a multidisciplinary Task Force to draw evidence-based guidelines for patients with brain metastases from solid tumors. Soffietti et al. present these guidelines, which provide a consensus review of evidence and recommendations for diagnosis by neuroimaging and neuropathology, staging, prognostic factors, and different treatment options. Specifically, they addressed options such as surgery, stereotactic radiosurgery/stereotactic fractionated radiotherapy, whole-brain radiotherapy, chemotherapy and targeted therapy (with particular attention to brain metastases from non-Small-cell lung cancer, melanoma and breast and renal cancer), and supportive care 5).
Zhu et al. reported a medium-throughput drug screening platform (METPlatform) based on organotypic cultures that allow evaluating inhibitors against metastases growing in situ. By applying this approach to the unmet clinical need of brain metastases, they identified several vulnerabilities. Among them, a blood-brain barrier permeable HSP90 inhibitor showed high potency against mouse and human brain metastases at clinically relevant stages of the disease, including a novel model of local relapse after neurosurgery. Furthermore, in situ proteomic analysis applied to metastases treated with the chaperone inhibitor uncovered a novel molecular program in brain metastases, which includes biomarkers of poor prognosis and actionable mechanisms of resistance. The work validates METPlatform as a potent resource for metastases research integrating drug screening and unbiased omics approaches that are compatible with human samples. Thus, this clinically relevant strategy is aimed to personalize the management of metastatic disease in the brain and elsewhere 6).