Bone and Soft Tissue Sarcoma, HDM2/MDM2

View:
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
CLICK IMAGE FOR MORE INFORMATION
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.

Source:
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.

Expand Collapse No mutation selected
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.

Share with your Physican

Print information for your Physician.

Print information

Your Matched Clinical Trials

Trial Matches: (D) - Disease, (G) - Gene
Trial Status: Showing all 10 results Per Page:
Protocol # Title Location Status Match
NCT03092323 A Randomized Trial of Pembrolizumab & Radiotherapy Versus Radiotherapy in High-Risk Soft Tissue Sarcoma of the Extremity A Randomized Trial of Pembrolizumab & Radiotherapy Versus Radiotherapy in High-Risk Soft Tissue Sarcoma of the Extremity 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
NCT03002805 CBT-1® in Combination With Doxorubicin in Patients With Metastatic, Unresectable Sarcomas Who Previously Progressed on Doxorubicin CBT-1® in Combination With Doxorubicin in Patients With Metastatic, Unresectable Sarcomas Who Previously Progressed on Doxorubicin MGH Open D
NCT03600649 Clinical Trial of SP-2577 (Seclidemstat) in Patients With Relapsed or Refractory Ewing or Ewing-related Sarcomas Clinical Trial of SP-2577 (Seclidemstat) in Patients With Relapsed or Refractory Ewing or Ewing-related Sarcomas MGH Open D
NCT02567435 Combination Chemotherapy With or Without Temsirolimus in Treating Patients With Intermediate Risk Rhabdomyosarcoma Combination Chemotherapy With or Without Temsirolimus in Treating Patients With Intermediate Risk Rhabdomyosarcoma MGH Open D
NCT03331250 Eribulin in Angiosarcoma and Epithelioid Hemangioendothelioma (EHE) Eribulin in Angiosarcoma and Epithelioid Hemangioendothelioma (EHE) 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 Olaparib and Temozolomide for Ewings Sarcoma or Rhabdoomyosarcoma Phase I Study of Olaparib and Temozolomide for Ewings Sarcoma or Rhabdoomyosarcoma MGH Open D
NCT03114527 Phase II Trial of Ribociclib and Everolimus in Advanced Dedifferentiated Liposarcoma (DDL) and Leiomyosarcoma (LMS) Phase II Trial of Ribociclib and Everolimus in Advanced Dedifferentiated Liposarcoma (DDL) and Leiomyosarcoma (LMS) MGH Open D
NCT01659203 Proton or Photon RT for Retroperitoneal Sarcomas Proton or Photon RT for Retroperitoneal Sarcomas 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:

Share with your Physican

Print information for your Physician.

Print information