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Klinik für Pädiatrische Hämatologie und Onkologie

Projekte AG Hettmer

Research in our lab aims at improving sarcoma treatment through a better understanding of sarcoma biology.

Sarcomas are a heterogeneous group of cancers arising in non-hematopoietic, mesodermal tissues. These tumors occur at any age, but many sarcomas are disproportionately common in children and adolescents. Most patients with high-risk metastatic disease die despite intensive therapy, and those who survive face lifelong, significant late effects of treatment. Sadly, therapeutic options have not really changed for decades. Identifying novel therapeutic strategies is an important, unmet clinical need.

Our work aims to address three important challenges:

(1) To establish robust sarcoma test platforms in vitro and in vivo with the goal of dissecting cellular, genetic and metabolic drivers of sarcoma.

We employ cell sorting and transplantation tools that open the way for comprehensive studies to (i) distinguish the sarcoma-initiating potential of functionally discrete mesodermal cell populations, (ii) identify oncogenic events that drive sarcoma induction and (iii) directly examine the oncogenic factors that determine sarcoma maintenance. Active work focuses on Ras-driven, fusion-negative and PAX3:FOXO1+ rhabdomyosarcoma in mice.

(2) To define biologically distinct sarcoma categories and identify subsets of disease with likely susceptibility to candidate interventions.

Fusion-negative rhabdomyosarcomas are a heterogeneous group of cancers with muscle differentiation. It is unlikely that marked differences in histology, differentiation and oncogenic pathway activation are randomly distributed. Our work aims to identify clinically and biologically distinct susbets on the fusion-negative rhabdomyosarcoma spectrum. We are currently investigating the genetic underpinnings of highly differentiated, rhabdomyoma-like rhabdomyosarcoma.

(3) To determine the genetic basis of sarcoma susceptibility.

Sarcoma susceptibility has been linked to specific cancer-predisposing germline mutations that may be inherited or may also arise de novo. I have shown that TP53 mutations, for example, confer a predisposition to develop anaplastic rhabdomyosarcomas in young children. Active work in the lab investigates SMN (second malignant neoplasm) rates in sarcoma survivors as a consequence of genetic predisposition.

Ärztliche Direktorin
Klinik für Pädiatrische Hämatologie und Onkologie

Mathildenstraße 1 (Postadresse)
Heiliggeiststraße 1 (Anfahrt)
79106 Freiburg

Telefon: 0761 270-45060
Telefax: 0761 270-45180