Bone and Soft Tissue Sarcoma, HDM2/MDM2, amplification

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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 amplification  in HDM2/MDM2
Genetic amplification of HDM2/MDM2 means that the segment of DNA that encodes HDM2/MDM2 has been replicated several times, so that there are multiple copies of the gene in the tumor cells. Multiple copies mean that the gene is transcribed more than the normal amount it would be were there only one copy of the gene. This additional transcription of HDM2/MDM2 results in higher than normal levels of the HDM2/MDM2 protein in cells. Since HDM2/MDM2 protein functions to destroy TP53, TP53 levels in the cell drop drastically. This leaves the cells unable to stop growing in response to DNA damage or other signals that would normally trigger TP53 to cause cell cycle arrest.
Genetic amplification of HDM2/MDM2 means that the segment of DNA that encodes HDM2/MDM2 has been replicated several times, so that there are multiple copies of the gene in the tumor cells. Multiple copies mean that the gene is transcribed more than the normal amount it would be were there only one copy of the gene. This additional transcription of HDM2/MDM2 results in higher than normal levels of the HDM2/MDM2 protein in cells. Since HDM2/MDM2 protein functions to destroy TP53, TP53 levels in the cell drop drastically. This leaves the cells unable to stop growing in response to DNA damage or other signals that would normally trigger TP53 to cause cell cycle arrest.

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Your Matched Clinical Trials

Trial Matches: (D) - Disease, (G) - Gene, (M) - Mutation
Trial Status: Showing all 10 results Per Page:
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
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
NCT02642016 A Study to Evaluate the Safety and Pharmacokinetics of KTN0158 in Adult Patients With Advanced Solid Tumors A Study to Evaluate the Safety and Pharmacokinetics of KTN0158 in Adult Patients 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
NCT02611024 Pharmacokinetic Study of PM01183 in Combination With Irinotecan in Patients With Selected Solid Tumors Pharmacokinetic Study of PM01183 in Combination With Irinotecan in Patients With Selected Solid Tumors MGH Open D
NCT01858168 Phase I Study of Olaprib and Temozolomide for Ewings Sarcoma Phase I Study of Olaprib and Temozolomide for Ewings Sarcoma MGH Open D
NCT01659203 Proton or Photon RT for Retroperitoneal Sarcomas Proton or Photon RT for Retroperitoneal Sarcomas MGH Open D
NCT02180867 Radiation Therapy With or Without Combination Chemotherapy or Pazopanib Hydrochloride Before Surgery in Treating Patients With Newly Diagnosed Non-Rhabdomyosarcoma Soft Tissue Sarcomas That Can Be Removed by Surgery Radiation Therapy With or Without Combination Chemotherapy or Pazopanib Hydrochloride Before Surgery in Treating Patients With Newly Diagnosed Non-Rhabdomyosarcoma Soft Tissue Sarcomas That Can Be Removed by Surgery MGH Open D
NCT02576431 Study of LOXO-101 in Subjects With NTRK Fusion Positive Solid Tumors (NAVIGATE) Study of LOXO-101 in Subjects With NTRK Fusion Positive Solid Tumors (NAVIGATE) MGH Open D
NCT02660034 The Safety, Pharmacokinetics and Antitumor Activity of the BGB-A317 in Combination With the BGB-290 in Subjects With Advanced Solid Tumors The Safety, Pharmacokinetics and Antitumor Activity of the BGB-A317 in Combination With the BGB-290 in Subjects With Advanced Solid Tumors MGH Open D
MGH has many open clinical trials for other cancers not shown on the Targeted Cancer Care website. They can be found on the MassGeneral.org clinical trials search page.

Additional clinical trials may be applicable to your search criteria, but they may not be available at MGH. These clinical trials can typically be found by searching the clinicaltrials.gov website.
Trial Status: Showing all 10 results Per Page:

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