Related Experiment Video
Updated: Dec 10, 2025
Modeling Brain Metastases Through Intracranial Injection and Magnetic Resonance Imaging
Published on: June 7, 2020
Management of brain metastases according to molecular subtypes
Riccardo Soffietti1, Manmeet Ahluwalia2, Nancy Lin3
1Department of Neuro-Oncology, University and City of Health and Science Hospital, Turin, Italy. riccardo.soffietti@unito.it.
Abstract:
The incidence of brain metastases has markedly increased in the past 20 years owing to progress in the treatment of malignant solid tumours, earlier diagnosis by MRI and an ageing population. Although local therapies remain the mainstay of treatment for many patients with brain metastases, a growing number of systemic options are now available and/or are under active investigation. HER2-targeted therapies (lapatinib, neratinib, tucatinib and trastuzumab emtansine), alone or in combination, yield a number of intracranial responses in patients with HER2-positive breast cancer brain metastases. New inhibitors are being investigated in brain metastases from ER-positive or triple-negative breast cancer. Several generations of EGFR and ALK inhibitors have shown activity on brain metastases from EGFR and ALK mutant non-small-cell lung cancer. Immune-checkpoint inhibitors (ICIs) hold promise in patients with non-small-cell lung cancer without druggable mutations and in patients with triple-negative breast cancer. The survival of patients with brain metastases from melanoma has substantially improved after the advent of BRAF inhibitors and ICIs (ipilimumab, nivolumab and pembrolizumab). The combination of targeted agents or ICIs with stereotactic radiosurgery could further improve the response rates and survival but the risk of radiation necrosis should be monitored. Advanced neuroimaging and liquid biopsy will hopefully improve response evaluation.
Insights
Systemic therapies are improving outcomes for brain metastases, with targeted agents and immune-checkpoint inhibitors showing efficacy in various cancers like breast, lung, and melanoma. Combinations with radiation may enhance responses but require monitoring for side effects.
Area of Science:
- Oncology
- Neurology
- Pharmacology
Background:
- Brain metastases incidence is rising due to better cancer treatment, earlier MRI diagnosis, and an aging population.
- While local therapies are standard, systemic treatment options for brain metastases are expanding.
- HER2-targeted therapies show intracranial responses in HER2-positive breast cancer brain metastases.
Purpose of the Study:
- To review current and emerging systemic therapies for brain metastases.
- To highlight the efficacy of targeted agents and immune-checkpoint inhibitors across different cancer types.
- To discuss the potential of combination therapies and future directions in managing brain metastases.
Main Methods:
- Review of recent advancements in systemic treatments for brain metastases.
- Analysis of clinical data for targeted therapies (HER2, EGFR, ALK, BRAF inhibitors) and immune-checkpoint inhibitors (ICIs).
- Discussion of combination strategies with stereotactic radiosurgery and the role of advanced neuroimaging and liquid biopsy.
Main Results:
- HER2-targeted therapies demonstrate intracranial activity in HER2-positive breast cancer.
- EGFR and ALK inhibitors are effective for relevant mutations in non-small-cell lung cancer brain metastases.
- BRAF inhibitors and ICIs have significantly improved survival for melanoma brain metastases.
- ICIs show promise for non-small-cell lung cancer without targetable mutations and triple-negative breast cancer.
Conclusions:
- Systemic therapies, including targeted agents and ICIs, offer significant progress in treating brain metastases.
- Combination therapies with stereotactic radiosurgery may improve outcomes but necessitate careful monitoring for radiation necrosis.
- Advanced neuroimaging and liquid biopsy are expected to enhance response evaluation and patient management.
