Bone and Soft Tissue Sarcoma, KIT

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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 KIT  - General Description
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The KIT gene (also known as CD117) encodes a transmembrane receptor that binds the ligand known as stem cell factor (SCF). Binding of the ligand SCF on the outside of the cell leads to the activation of the KIT receptor tyrosine kinase inside the cell. When tyrosine kinases are activated, they become phosphorylated, meaning they have phosphate added at specific sites on the portion of the receptor that is inside the cell. These phosphorylation sites serve as docking sites for the assembly of signal proteins that then cause the activation of several signal pathways. When KIT is activated, it specifically activates the MAP kinase pathway, the PI3K/AKT/mTOR pathway, and the JAK/STAT pathway. When activated, these signal pathways promote cellular proliferation and survival.

In studies examining the KIT protein in cancers, mutations in KIT have been identified that lead to the production of an altered protein that cannot be regulated normally. Invariably, the mutated KIT protein found in tumors no longer needs SCF ligand binding to the external portion of the receptor to be activated. Instead, mutated KIT stays in a constantly activated state. This constant stimulation of growth and survival signal pathways can leads to the development of cancer. Mutations and other genetic alterations in the gene encoding KIT have been found in several tumor types. Mutations in the KIT protein are frequently found in GastroIntestinal Stromal Tumors (GIST), in some types of Acute Myeloid Leukemia (AML), in melanoma, and less frequently in some other types of tumors. Clinical trials involving KIT inhibitors, as well as KIT inhibitors used in combination with other therapeutic agents are underway at the MGH Cancer Center. Further studies are needed to prevent the growth of tumors containing KIT alterations.
The KIT gene (also known as CD117) encodes a transmembrane receptor that binds the ligand known as stem cell factor (SCF). Binding of the ligand SCF on the outside of the cell leads to the activation of the KIT receptor tyrosine kinase inside the cell. When tyrosine kinases are activated, they become phosphorylated, meaning they have phosphate added at specific sites on the portion of the receptor that is inside the cell. These phosphorylation sites serve as docking sites for the assembly of signal proteins that then cause the activation of several signal pathways. When KIT is activated, it specifically activates the MAP kinase pathway, the PI3K/AKT/mTOR pathway, and the JAK/STAT pathway. When activated, these signal pathways promote cellular proliferation and survival.

In studies examining the KIT protein in cancers, mutations in KIT have been identified that lead to the production of an altered protein that cannot be regulated normally. Invariably, the mutated KIT protein found in tumors no longer needs SCF ligand binding to the external portion of the receptor to be activated. Instead, mutated KIT stays in a constantly activated state. This constant stimulation of growth and survival signal pathways can leads to the development of cancer. Mutations and other genetic alterations in the gene encoding KIT have been found in several tumor types. Mutations in the KIT protein are frequently found in GastroIntestinal Stromal Tumors (GIST), in some types of Acute Myeloid Leukemia (AML), in melanoma, and less frequently in some other types of tumors. Clinical trials involving KIT inhibitors, as well as KIT inhibitors used in combination with other therapeutic agents are underway at the MGH Cancer Center. Further studies are needed to prevent the growth of tumors containing KIT alterations.

PubMed ID's
9438854, 15339674, 15948115, 16647948, 17372901, 16908931
Expand Collapse KIT  in Bone and Soft Tissue Sarcoma
Patients with gastrointestinal stromal tumors that carry mutations in exon 11 of the KIT gene are mostly responsive to imatinib therapy, with improvements in recurrence-free survival when compared to placebo. Gastrointestinal stromal tumors with mutations in exon 9 are, however, comparatively less responsive. The presence of mutations in KIT exons other than 9 and 11 can predict for resistance to imatinib treatment.

Mutations at amino acid position D816 in exon 17 of the KIT gene are rare and have been identified as a secondary mutation that occurs in imatinib-resistant tumors. However, these mutations may promote sensitivity to the inhibitor dasatinib.

Patients with gastrointestinal stromal tumors that carry mutations in exon 11 of the KIT gene are mostly responsive to imatinib therapy, with improvements in recurrence-free survival when compared to placebo. Gastrointestinal stromal tumors with mutations in exon 9 are, however, comparatively less responsive. The presence of mutations in KIT exons other than 9 and 11 can predict for resistance to imatinib treatment.

Mutations at amino acid position D816 in exon 17 of the KIT gene are rare and have been identified as a secondary mutation that occurs in imatinib-resistant tumors. However, these mutations may promote sensitivity to the inhibitor dasatinib.

PubMed ID's
21387287, 15365079, 18955451
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.

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Your Matched Clinical Trials

Trial Matches: (D) - Disease, (G) - Gene
Trial Status: Showing all 7 results Per Page:
Protocol # Title Location Status Match
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 Participants 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 Participants 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
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
NCT02106312 Dose Reduction of Preoperative Radiotherapy in Myxoid Liposarcomas Dose Reduction of Preoperative Radiotherapy in Myxoid Liposarcomas MGH Open D
NCT01858168 Phase I Study of Olaparib and Temozolomide for Ewings Sarcoma Phase I Study of Olaparib 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
NCT02048371 SARC024: A Blanket Protocol to Study Oral Regorafenib in Patients With Selected Sarcoma Subtypes SARC024: A Blanket Protocol to Study Oral Regorafenib in Patients With Selected Sarcoma Subtypes 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 7 results Per Page:

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