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The development of brain metastases is a common condition of melanoma and is associated with
a poor prognosis in affected patients.
The effectiveness of existing therapies varies widely
.
However, the reasons for this discrepancy remain largely unknown
.
An international team of researchers, led by the University of Veterinary Medicine in Vienna, has now combined several analytical methods and was able to identify two molecularly distinct subsets of melanoma brain metastases to explain the differential response
to treatment.
The effects of therapeutic interventions for the treatment of metastatic melanoma of the brain (MBMs) vary widely, with corresponding prognosis for individual patients
.
However, the mechanisms that control response to treatment are unclear
.
In an international study led by Vetmeduni, researchers used an interdisciplinary combination of multiple analytical methods, including targeted gene sequencing (TargetSeq), to reveal for the first time molecular programs
that may control the development of brain metastases.
The study's last author, Torben Redmer from the Institute of Medical Biochemistry and Pathology in Vetmeduni, summed up the main findings: "Our study provides evidence that MBMs can be divided into at least two subgroups
.
In this regard, it is important to regulate molecular programs
related to the expression of adhesion protein e-cadherin (Ecad) and nerve growth factor receptor (NGFR).
Although ECAD-related programs mainly occurred in therapy-naåve MBMs, i.
e.
, tumors that still respond to treatment measures, we found higher levels of NGFR in drug-resistant MBMs
.
Thus, phenotypic changes from Ecad to NGFR may determine different treatment responses of tumors and may represent the main marker of progressive MBMs, namely rapid progression
.
”
According to the researchers, further research is now needed to fully explain the molecular programs
that drive the occurrence and progression of single and multiple brain metastases in melanoma.
The need for further research also applies to other cancers with a high incidence of brain metastases, such as lung and breast cancer
.
Brain metastases are common
in melanoma, lung, and breast cancer.
Despite tremendous progress and significant responses in some patient populations, treatments developed to date have not been sufficient to achieve long-term prevention
of disease recurrence and progression.
The latter is determined by the presence of multiple brain metastases and is therefore associated with
a poor prognosis.
MBMs
occur in 20-40% of melanoma patients.
The median overall survival after the discovery of MBMs was only 8.
9 months
.
