Insight

Uta Dirksen: I was part of a guest Editor team on a special issue on Ewing sarcoma

Photo taken from Uta Dirksen/LinkedIn

Nov 26, 2023, 17:41

Uta Dirksen: I was part of a guest Editor team on a special issue on Ewing sarcoma

Uta Dirksen, Vice Director Pediatrics III at the University of Duisburg-Essen, University Hospital, shared on LinkedIn:

“Dear all, I was part of a guest Editor team on a special issue on Ewing sarcoma. Together with Poul Sorensen and Stefan Burdach. Here comes part of our intro. Feel free to check out!

Ewing sarcomas are characterized by unique ews/ets translocations, which constitute prototypic oncogenic drivers. However, these oncofusions do not determine clinical biology and outcome. Patient fate is almost exclusively determined by metastasis and both the high propensity and the complex process of spread are far from being completely understood.

Ewing sarcomas are amongst childhood cancers with a low mutational rate, making reliable biomarkers elusive. Mutation rates increase, however, with relapse and cumulative mutagenic therapy exposure. However, a silent tumor genome generally limits targeted therapy approaches, which applies particularly for Ewing sarcoma.

Precision oncology approaches, nevertheless, aim at enhancing the therapeutic index of conventional chemotherapy with novel small molecules targeting epigenetics, metabolism and the stress response. Albeit their genome is generally silent, Ewing sarcomas reactivate endogenous retroelements. Their activation is linked to a particular inflammatory response and a prometastatic modulation of the microenvironment.

On the other hand, Ewing sarcomas are characterized, at least in most cases, by immune inertia, i.e., a scarcity of T cell infiltrates and a predominance of immunosuppressive myeloid signatures (M0/M2), leading to the antagonistic processes of inflammation and immunosuppression. These suppressive myeloid cells shield the tumor against adaptive immune attack, hampering the efficacy of chimeric antigen receptor or T cell receptor transgenic T cells.

Overcoming these immunosuppressive mechanisms may enhance immunotherapeutic efficacy. One approach in this regard is the utilization of oncolytic viruses, genetically engineered to depend on their lytic cycle from metastatic drivers. They can induce immunogenic cell death and, particularly when in combination with cell cycle inhibitors, do have the potential to also overcome barriers to immunotherapy in Ewing sarcoma.”

For the full article click here.
Source: Uta Dirksen/LinkedIn