Bone and Soft Tissue Sarcoma, PIK3CA, activating mutations

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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 PIK3CA  - General Description
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PIK3CA is a gene that provides the code for making one piece of the phosphatidylinositol 3-kinase (PI3K) protein, which is an enzyme that is part of an important signaling pathway (PI3K/AKT) involved in controlling the growth, division, survival, nutrient utilization, movement and structure of cells. PIK3CA encodes the catalytic subunit of PI3K, which is the part of the protein that lets it function as an enzyme. PI3K function is tightly maintained in normal cells. The enzymatic activity is activated by specific signals from growth factor receptor tyrosine kinases (RTKs) or from activated RAS proteins. PI3K then generates molecules that attract another enzyme (particularly AKT) to the cell membrane, where it is activated. The activated AKT acts on other proteins that regulate various cell processes that promotes cell growth and survival.

Mutations in PIK3CA lead to enhanced activation of its signaling function, thereby driving the tumorigenic process. These activating mutations are commonly associated with breast and colon cancer, and more rarely with melanoma of the skin. Defects in this gene have also been associated with ovarian cancer, endometrial cancer, and liver cancer.

Tumor mutation profiling performed clinically at the MGH Cancer Center has identified PIK3CA mutations across a broad-spectrum of cancer types. The highest incidence of PIK3CA mutations have been found in endometrial cancer (25%), breast cancer (20%), colon cancer (25%) and cancers of the head and neck (10%). In the other major tumor types, PIK3CA mutations have been found in less than 10% of cases that have been tested. The MGH Cancer Center is a world leader in the treatment of PIK3CA mutated tumors, as well as in the number of clinical trials available for treatment with new therapies against tumors with PIK3CA mutations.

Sources: Genetics Home Reference
The PIK3CA gene encodes the p110 alpha catalytic subunit of the phosphoinositol 3-kinase (PI3K) complex. PI3K receives upstream activation signals from growth factor receptor tyrosine kinases (e.g. EGFR family members), and in turn signals through AKT and mTOR in order to promote cell survival, cell growth and cellular proliferation. PIK3CA mutations lead to increased activation of PI3K/AKT/mTOR signaling. PI3K function is opposed by PTEN, a lipid phosphatase that is often inactivated by mutations or silenced by methylation in many cancers.

Tumor mutation profiling performed clinically at the MGH Cancer Center has identified PIK3CA mutations across a broad-spectrum of cancer types. The highest incidence of PIK3CA mutations have been found in endometrial cancer (25%), breast cancer (20%), colon cancer (25%) and cancers of the head and neck (10%). In the other major tumor types, PIK3CA mutations have been found in less than 10% of cases that have been tested.

Sources: Genetics Home Reference
Expand Collapse activating mutations  in PIK3CA
Many of the mutations in PIK3CA associated with tumors are gain of function mutations, rendering the kinase in a constantly activated state. Instead of reacting to appropriate stimulation to induce a growth signal, activating mutations keep the PI3 Kinase in a constant state of stimulating growth.
Many of the mutations in PIK3CA associated with tumors are gain of function mutations, rendering the kinase in a constantly activated state. Instead of reacting to appropriate stimulation to induce a growth signal, activating mutations keep the PI3 Kinase in a constant state of stimulating growth.

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Your Matched Clinical Trials

Trial Matches: (D) - Disease, (G) - Gene, (M) - Mutation
Trial Status: Showing Results: 1-10 of 26 Per Page:
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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
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
NCT02748135 A Two-Part Study of TB-403 in Pediatric Subjects With Relapsed or Refractory Medulloblastoma A Two-Part Study of TB-403 in Pediatric Subjects With Relapsed or Refractory Medulloblastoma 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 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
NCT02867592 Cabozantinib-S-Malate in Treating Younger Patients With Recurrent, Refractory, or Newly Diagnosed Sarcomas, Wilms Tumor, or Other Rare Tumors Cabozantinib-S-Malate in Treating Younger Patients With Recurrent, Refractory, or Newly Diagnosed Sarcomas, Wilms Tumor, or Other Rare Tumors 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
NCT02454972 Clinical Trial of Lurbinectedin (PM01183) in Selected Advanced Solid Tumors Clinical Trial of Lurbinectedin (PM01183) in Selected Advanced Solid Tumors MGH Open D
Trial Status: Showing Results: 1-10 of 26 Per Page:
123Next »

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