Métastase cérébrale | EPFL Graph Search

Une métastase cérébrale est une dissémination de cellules cancéreuses (Métastases) dans le tissu cérébral. Cela désigne des tumeurs malignes originant de l'extérieur du cerveau. Les métastase cérébrales viennent souvent du cancer du poumon, du cancer du sein, du cancer du rein et de mélanome malin. Ce sont les tumeurs les plus fréquentes au niveau du cerveau. Elles peuvent se faire sentir, entre autres, par des maux de tête, des troubles neurologiques, des convulsions et des changements d'attitude. Le traitement et les chances de guérison dépendent de nombreux facteurs, mais les métastases cérébrales ont généralement un pronostic défavorable. Nomenclature

Une métastase cérébrale isolée, est la seule métastase à côté de la tumeur primitive. Elle se caractérise par l'absence d'autres métastases en dehors du système nerveux central.
Lors d'une métastase cérébrale singulière en revanche, il y a d'autres métastases en dehors du système nerveux central.
Les métastases l

Tumour exosomal CEMIP protein promotes cancer cell colonization in brain metastasis

Yan Liu, Etienne Meylan, Gonçalo Rodrigues, Loïc Steiner

The development of effective therapies against brain metastasis is currently hindered by limitations in our understanding of the molecular mechanisms driving it. Here we define the contributions of tumour-secreted exosomes to brain metastatic colonization and demonstrate that pre-conditioning the brain microenvironment with exosomes from brain metastatic cells enhances cancer cell outgrowth. Proteomic analysis identified cell migration-inducing and hyaluronan-binding protein (CEMIP) as elevated in exosomes from brain metastatic but not lung or bone metastatic cells. CEMIP depletion in tumour cells impaired brain metastasis, disrupting invasion and tumour cell association with the brain vasculature, phenotypes rescued by pre-conditioning the brain microenvironment with CEMIP exosomes. Moreover, uptake of CEMIP+ exosomes by brain endothelial and microglial cells induced endothelial cell branching and inflammation in the perivascular niche by upregulating the pro-inflammatory cytokines encoded by Ptgs2, Tnf and Ccl/Cxcl, known to promote brain vascular remodelling and metastasis. CEMIP was elevated in tumour tissues and exosomes from patients with brain metastasis and predicted brain metastasis progression and patient survival. Collectively, our findings suggest that targeting exosomal CEMIP could constitute a future avenue for the prevention and treatment of brain metastasis.

NATURE PUBLISHING GROUP2019

The combination of stereotactic radiosurgery with immune checkpoint inhibition or targeted therapy in melanoma patients with brain metastases: a retrospective study

Filipe Amândio Brandão Sanches Vong Martins, Krisztian Homicsko, Olivier Michielin, Constantin Tuleasca, Alexandre Wicky

Background Evidence pointing to a synergistic effect of stereotactic radiosurgery (SRS) with concurrent immunotherapy or targeted therapy in patients with melanoma brain metastases (BM) is increasing. We aimed to analyze the effect on overall survival (OS) of immune checkpoint inhibitors (ICI) or BRAF/MEK inhibitors initiated during the 9 weeks before or after SRS. We also evaluated the prognostic value of patients' and disease characteristics as predictors of OS in patients treated with SRS. Methods We identified patients with BM from cutaneous or unknown primary origin melanoma treated with SRS between 2011 and 2018. Results We included 84 patients. The median OS was 12 months (95% CI 9-20 months). The median follow-up was 30 months (95% CI 28-49). Twenty-eight patients with newly diagnosed BM initiated anti-PD-1 +/-CTLA-4 therapy (n = 18), ipilimumab monotherapy (n = 10) or BRAF+/- MEK inhibitors (n = 11), during the 9 weeks before or after SRS. Patients who received anti-PD-1 +/-CTLA-4 mAb showed an improved survival in comparison to ipilimumab monotherapy (OS 24 vs. 7.5 months; HR 0.32, 95% 0.12-0.83, p = 0.02) and BRAF +/-MEK inhibitors (OS 24 vs. 7 months, respectively; HR 0.11, 95% 0.04-0.34, p = 0.0001). This benefit remained significant when compared to the subgroup of patients treated with dual BRAF/MEK inhibition (BMi) (n = 5). In a multivariate Cox regression analysis an age > 65, synchronous BM, > 2 metastatic sites, > 4 BM, and an ECOG > 1 were correlated with poorer prognosis. A treatment with anti-PD-1+/-CTLA-4 mAbs within 9 weeks of SRS was associated with better outcomes. The presence of serum lactate dehydrogenase (LDH) levels >= 2xULN at BM diagnosis was associated with lower OS (HR 1.60, 95% CI 1.03-2.50; p = 0.04). Conclusions The concurrent administration of anti-PD-1+/-CTLA-4 mAbs with SRS was associated with improved survival in melanoma patients with newly diagnosed BM. In addition to CNS tumor burden, the extension of systemic disease retains its prognostic value in patients treated with SRS. Elevated serum LDH levels are predictors of poor outcome in these patients.

SPRINGER2020

Synaptic proximity enables NMDAR signalling to promote brain metastasis

Giovanni Ciriello, Douglas Hanahan, Wei Jiao, Graham Knott, Brian Donal McCabe, Iacovos Michael, Mohammad Sadegh Saghafinia, Qiqun Zeng, Peng Zhang

Metastasis-the disseminated growth of tumours in distant organs-underlies cancer mortality. Breast-to-brain metastasis (B2BM) is a common and disruptive form of cancer and is prevalent in the aggressive basal-like subtype, but is also found at varying frequencies in all cancer subtypes. Previous studies revealed parameters of breast cancer metastasis to the brain, but its preference for this site remains an enigma. Here we show that B2BM cells co-opt a neuronal signalling pathway that was recently implicated in invasive tumour growth, involving activation by glutamate ligands of N-methyl-D-aspartate receptors (NMDARs), which is key in model systems for metastatic colonization of the brain and is associated with poor prognosis. Whereas NMDAR activation is autocrine in some primary tumour types, human and mouse B2BM cells express receptors but secrete insufficient glutamate to induce signalling, which is instead achieved by the formation of pseudo-tripartite synapses between cancer cells and glutamatergic neurons, presenting a rationale for brain metastasis.

2019

The combination of stereotactic radiosurgery with immune checkpoint inhibition or targeted therapy in melanoma patients with brain metastases: a retrospective study

Filipe Amândio Brandão Sanches Vong Martins, Krisztian Homicsko, Olivier Michielin, Constantin Tuleasca, Alexandre Wicky

SPRINGER2020