Bone and Soft Tissue Sarcoma, HDM2/MDM2

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Expand Collapse Bone and Soft Tissue Sarcoma  - General Description This year about 12,000 people in the U.S. will be told by a doctor that they have cancer of the soft tissue. Sarcomas develop more commonly in adults, although certain types of sarcoma are found more typically in children.

Soft tissue sarcomas can form almost anywhere in the body, including cartilage, fat, muscle, fibrous tissue, blood vessels, and other connective or supportive tissues; osteosarcomas develop in bone, liposarcomas form in fat; rhabdomyosarcomas form in muscle; Ewing sarcomas form in bone and soft tissue; Kaposi sarcoma and uterine sarcoma are other types of soft tissue sarcomas. Because there are many types of soft tissue sarcoma, the cell type must be identified before treatment decisions are made. There are ongoing clinical trials using many forms of therapy in specific types of sarcoma.

Source: National Cancer Institute, 2017
This year about 12,000 people in the U.S. will be told by a doctor that they have cancer of the soft tissue. Sarcomas develop more commonly in adults, although certain types of sarcoma are found more typically in children.

Soft tissue sarcomas can form almost anywhere in the body, including cartilage, fat, muscle, fibrous tissue, blood vessels, and other connective or supportive tissues; osteosarcomas develop in bone, liposarcomas form in fat; rhabdomyosarcomas form in muscle; Ewing sarcomas form in bone and soft tissue; Kaposi sarcoma and uterine sarcoma are other types of soft tissue sarcomas. Because there are many types of soft tissue sarcoma, the cell type must be identified before treatment decisions are made. There are ongoing clinical trials using many forms of therapy in specific types of sarcoma.

Source: National Cancer Institute, 2017
This year about 12,000 people in the U.S. will be told by a doctor that they have cancer of the soft tissue. Sarcomas develop more commonly in adults, although certain types of sarcoma are found more typically in children.

Soft tissue sarcomas can form almost anywhere in the body, including cartilage, fat, muscle, fibrous tissue, blood vessels, and other connective or supportive tissues; osteosarcomas develop in bone, liposarcomas form in fat; rhabdomyosarcomas form in muscle; Ewing sarcomas form in bone and soft tissue; Kaposi sarcoma and uterine sarcoma are other types of soft tissue sarcomas. Because there are many types of soft tissue sarcoma, the cell type must be identified before treatment decisions are made. There are ongoing clinical trials using many forms of therapy in specific types of sarcoma.

Source: National Cancer Institute, 2017
This year about 12,000 people in the U.S. will be told by a doctor that they have cancer of the soft tissue. Sarcomas develop more commonly in adults, although certain types of sarcoma are found more typically in children.

Soft tissue sarcomas can form almost anywhere in the body, including cartilage, fat, muscle, fibrous tissue, blood vessels, and other connective or supportive tissues; osteosarcomas develop in bone, liposarcomas form in fat; rhabdomyosarcomas form in muscle; Ewing sarcomas form in bone and soft tissue; Kaposi sarcoma and uterine sarcoma are other types of soft tissue sarcomas. Because there are many types of soft tissue sarcoma, the cell type must be identified before treatment decisions are made. There are ongoing clinical trials using many forms of therapy in specific types of sarcoma.

Source: National Cancer Institute, 2017
Expand Collapse HDM2/MDM2  - General Description
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HDM2, the human version of mouse MDM2 is a protein that negatively regulates the TP53 tumor suppressor protein. HDM2/MDM2 is one of a family of proteins in the ubiquitin proteolytic pathway that regulate proteins by targeting them for degradation. HDM2/MDM2 binds to and inactivates TP53, which is a tumor suppressor that causes growth arrest when cells suffer trauma or DNA damage. Growth arrest allows cells to repair their DNA prior to resuming growth. In some cancers, HDM2/MDM2 is genetically altered, causing production of more HDM2/MDM2 than is normally in cells. This abundance of HDM2/MDM2 binds to TP53, inducing its degradation, and without TP53, the cell cannot stop growing to repair damaged DNA before continuing to divide. Cell division that continues despite damaged DNA is more likely to lead to cancer.

Source:
HDM2, the human version of mouse MDM2 is a protein that negatively regulates the TP53 tumor suppressor protein. HDM2/MDM2 is one of a family of proteins in the ubiquitin proteolytic pathway that regulate proteins by targeting them for degradation. HDM2/MDM2 binds to and inactivates TP53, which is a tumor suppressor that causes growth arrest when cells suffer trauma or DNA damage. Growth arrest allows cells to repair their DNA prior to resuming growth. In some cancers, HDM2/MDM2 is genetically altered, causing production of more HDM2/MDM2 than is normally in cells. This abundance of HDM2/MDM2 binds to TP53, inducing its degradation, and without TP53, the cell cannot stop growing to repair damaged DNA before continuing to divide. Cell division that continues despite damaged DNA is more likely to lead to cancer.

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Expand Collapse HDM2/MDM2  in Bone and Soft Tissue Sarcoma
HDM2/MDM2 has been found to be genetically amplified in some sarcomas, resulting in excess HDM2/MDM2 protein being produced. The high concentration of HDM2/MDM2 destroys the TP53 tumor suppressor, rendering it unable to cause growth arrest when there is DNA damage to the cells. Cells that do not stop to repair damaged DNA before dividing contribute to the development of tumors.

The implications of amplification of HDM2/MDM2 in sarcomas are currently under study. New inhibitors of HDM2/MDM2 are currently in clinical trials being tested in sarcoma patients. More studies are needed to establish HDM2/MDM2 inhibitors as effective therapy in HDM2/MDM2 amplified sarcoma.

HDM2/MDM2 has been found to be genetically amplified in some sarcomas, resulting in excess HDM2/MDM2 protein being produced. The high concentration of HDM2/MDM2 destroys the TP53 tumor suppressor, rendering it unable to cause growth arrest when there is DNA damage to the cells. Cells that do not stop to repair damaged DNA before dividing contribute to the development of tumors.

The implications of amplification of HDM2/MDM2 in sarcomas are currently under study. New inhibitors of HDM2/MDM2 are currently in clinical trials being tested in sarcoma patients. More studies are needed to establish HDM2/MDM2 inhibitors as effective therapy in HDM2/MDM2 amplified sarcoma.

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The mutation of a gene provides clinicians with a very detailed look at your cancer. Knowing this information could change the course of your care. To learn how you can find out more about genetic testing please visit http://www.massgeneral.org/cancer/news/faq.aspx or contact the Cancer Center.

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Your Matched Clinical Trials

Trial Matches: (D) - Disease, (G) - Gene
Trial Status: Showing Results: 1-10 of 19 Per Page:
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Protocol # Title Location Status Match
NCT02601950 A Phase II, Multicenter Study of the EZH2 Inhibitor Tazemetostat in Adult Subjects With INI1-Negative Tumors or Relapsed/Refractory Synovial Sarcoma A Phase II, Multicenter Study of the EZH2 Inhibitor Tazemetostat in Adult Subjects With INI1-Negative Tumors or Relapsed/Refractory Synovial Sarcoma MGH Open D
NCT02659020 A Study of Olaratumab (LY3012207) in Participants With Advanced Soft Tissue Sarcoma A Study of Olaratumab (LY3012207) in Participants With Advanced Soft Tissue Sarcoma MGH Open D
NCT03126591 A Study of Olaratumab (LY3012207) Plus Pembrolizumab in Participants With Advanced or Metastatic Soft Tissue Sarcoma A Study of Olaratumab (LY3012207) Plus Pembrolizumab in Participants With Advanced or Metastatic Soft Tissue Sarcoma MGH Open D
NCT00585195 A Study Of Oral PF-02341066, A C-Met/Hepatocyte Growth Factor Tyrosine Kinase Inhibitor, In Patients With Advanced Cancer A Study Of Oral PF-02341066, A C-Met/Hepatocyte Growth Factor Tyrosine Kinase Inhibitor, In Patients With Advanced Cancer MGH Open D
NCT02278250 An Open-Label Study of the Safety, Tolerability, and Pharmacokinetic/Pharmacodynamic Profile of VX-803/M4344 as a Single Agent and in Combination With Cytotoxic Chemotherapy in Subjects With Advanced Solid Tumors An Open-Label Study of the Safety, Tolerability, and Pharmacokinetic/Pharmacodynamic Profile of VX-803/M4344 as a Single Agent and in Combination With Cytotoxic Chemotherapy in Subjects With Advanced Solid Tumors MGH Open D
NCT02568267 Basket Study of Entrectinib (RXDX-101) for the Treatment of Patients With Solid Tumors Harboring NTRK 1/2/3 (Trk A/B/C), ROS1, or ALK Gene Rearrangements (Fusions) Basket Study of Entrectinib (RXDX-101) for the Treatment of Patients With Solid Tumors Harboring NTRK 1/2/3 (Trk A/B/C), ROS1, or ALK Gene Rearrangements (Fusions) MGH Open D
NCT02454972 Clinical Trial of Lurbinectedin (PM01183) in Selected Advanced Solid Tumors Clinical Trial of Lurbinectedin (PM01183) in Selected Advanced Solid Tumors MGH Open D
NCT02306161 Combination Chemotherapy With or Without Ganitumab in Treating Patients With Newly Diagnosed Metastatic Ewing Sarcoma Combination Chemotherapy With or Without Ganitumab in Treating Patients With Newly Diagnosed Metastatic Ewing Sarcoma MGH Open D
NCT02106312 Dose Reduction of Preoperative Radiotherapy in Myxoid Liposarcomas Dose Reduction of Preoperative Radiotherapy in Myxoid Liposarcomas MGH Open D
NCT02978859 MGCD516 in Advanced Liposarcoma and Other Soft Tissue Sarcomas MGCD516 in Advanced Liposarcoma and Other Soft Tissue Sarcomas MGH Open D
Trial Status: Showing Results: 1-10 of 19 Per Page:
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