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Doxorubicin Hydrochloride or Trabectedin in Treating Patients With Previously Untreated Advanced or Metastatic Soft Tissue Sarcoma

ABSTRACT: RATIONALE: Drugs used in chemotherapy, such as doxorubicin hydrochloride and trabectedin, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. It is not yet known whether trabectedin is more effective than doxorubicin hydrochloride in treating patients with advanced or metastatic soft tissue sarcoma. PURPOSE: This randomized phase II/III trial is studying the safety of trabectedin compared with doxorubicin hydrochloride and to see how well they work in treating patients with advanced or metastatic soft tissue sarcoma.

DISEASE(S): Soft Tissue Sarcomas,Histologically Proven Advanced And/or Metastatic Malignant Soft Tissue Sarcoma Intermediate/high Grade, Excluding The Following Tumor Types : Well-differentiated Liposarcoma Embryonal Rhabdomyosarcoma Chondrosarcoma (excluding Extraskeletal Myxoid Chondrosarcoma) Osteosarcoma (excluding Extraskeletal Osteosarcoma) Ewing Tumors / Primitive Neuroectodermal Tumor (pnet) Gastro-intestinal Stromal Tumors (gist) Dermatofibrosarcoma Protuberans,Sarcoma,Histologically Proven Advanced And/or Metastatic Malignant Soft Tissue Sarcoma Intermediate/high Grade, Excluding The Following Tumor Types : Well-differentiated Liposarcoma Embryonal Rhabdomyo...

PROVIDER: 2094138 | ecrin-mdr-crc |

REPOSITORIES: ECRIN MDR

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Hypoxia and Intrinsic Transcriptomic Subtyping of Soft Tissue Sarcoma

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The role of Ng2/Cspg4 in soft tissues sarcoma

Project description:NG2/CSPG4 is expressed in soft tissue sarcomas, however, its function in this tumor type, and its capacity to serve as a therapeutic target are unknown. Here, we used genetically engineered mice and cells from human tumors to determine the function of Ng2/Cspg4 in soft tissue sarcoma initiation and growth. We also investigated the potential for NG2/CSPG4 mAb immunotherapy to target human sarcomas established as xenografts in mice. Inhibiting Ng2/Cspg4 expression in established soft tissue sarcomas is associated with a smaller tumor volume and a reduction in cell proliferation. Intriguingly, deleting Ng2/Cspg4 at the time of tumor initiation has the opposite effect. Gene profiling found that Igfbp3/5 are substantially downregulated when Ng2/Cspg4 is depleted at the time of tumor initiation, but upregulated or only minimally downregulated when Ng2/Cspg4 is depleted after tumor initiation. Furthermore, the normal regulation of Igfbp is blunted when Ng2/Cspg4 is deleted at the time of tumor initiation. Our data show a difference in NG2/CSPG4 function in tumor initiation and maintenance, and provides pre-clinical evidence supporting NG2/CSPG4 as a therapeutic approach in soft tissue sarcoma.

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