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TRK 1,2,3, in-frame deletion

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Expand Collapse TRK 1,2,3  - General Description The Tropomyosin receptor kinase (Trk) family has three members, Trk A, Trk B, and Trk C. They are encoded by three separate genes, NTRK1, NTRK2, and NTRK 3, respectively. Each has an external domain outside the cell membrane that can bind ligand, a transmembrane domain that traverses the cell membrane, and an intracellular domain that transmits the signal if ligand-binding occurs. The normal function of these tyrosine kinase cell surface receptors is on neuronal cells, where they have important roles in the development and activity of the nervous system. TrkA, TrkB and TrkC are each activated by a different neurotrophin (NT) ligand, and when stimulated by the appropriate NT ligand, multiple single receptors cluster together and phosphates are added to the intracellular domain of the receptors. This activates a specific signal cascade inside the cell, resulting in cell differentiation, cell survival, and/or cell proliferation. As can be seen in the graphic above, the TrkA receptor is activated by Nerve Growth Factor (NGF), the TrkB receptor is activated by Brain-Derived Growth Factor (BDNF) or NT4/5, and the TrkC receptor is activated by NT3. In development under normal conditions, when the Trk receptor binds to its specific NT ligand, different signal pathways within the cell are activated (see graphic above). When TrkA binds NGF, the Ras/MAP kinase pathway is activated, along with PLC gamma and PI3K, which leads to cell proliferation. When TrkB binds BDNF, the Ras-ERK pathway is activated, as well as activating the PI3K and PLC gamma pathways, leading to neuronal cell differentiation and survival. When TrkC binds NT3, the PI3 and AKT pathways are activated, insuring cell survival. The regulation of each of these receptors is critical to normal neuronal development. In cancer, Trk receptors are dysregulated due to one of several genetic alterations that prevent the normal regulation of the signals controlled by the receptors. The most clinically relevant genetic alteration that has been found in the Trk receptors in cancer is called a gene fusion, where a portion of the NTRK gene encoding the Trk receptor has broken from the rest of the gene, and has become attached to a portion of another gene. In the case of gene fusions with Trk receptors, the fusion Trk proteins no longer require their specific ligand to activate signal pathways within the cell, but instead are continually activated. They have lost their normal negative regulation, and send constant proliferation signals to the cell, promoting cancer growth and survival. Other genetic alterations in NTRK genes that have been found in cancers include mutations, in-frame deletions of the gene, and alternative splicing. Both in-frame deletions and alternative splicing result in a Trk receptor that is missing specific regions of the protein. Many different NTRK gene fusions have been identified in tumors. Recently, drug companies have developed multiple Trk inhibitors as possible treatments for aberrant Trk proteins in cancer. Some of these Trk inhibitors are currently in clinical trials at MGH and at other cancer centers. Additional Trk inhibitors are also under development by pharmaceutical companies, and will soon be in patient clinical trials. More studies are needed to determine which Trk inhibitors are the most effective against specific NTRK genetic alterations in specific tumors. Graphic was adapted from the article, NTRK gene fusions as novel targets of cancer therapy across multiple tumour types. Authors: Alessio Amatu, Andrea Sartore-Bianchi, and Salvatore Siena. ESMO Open 2016:1e000023. The Tropomyosin receptor kinase (Trk) family has three members, Trk A, Trk B, and Trk C. They are encoded by three separate genes, NTRK1, NTRK2, and NTRK 3, respectively. Each has an external domain outside the cell membrane that can bind ligand, a transmembrane domain that traverses the cell membrane, and an intracellular domain that transmits the signal if ligand-binding occurs. The normal function of these tyrosine kinase cell surface receptors is on neuronal cells, where they have important roles in the development and activity of the nervous system. TrkA, TrkB and TrkC are each activated by a different neurotrophin (NT) ligand, and when stimulated by the appropriate NT ligand, multiple single receptors cluster together and phosphates are added to the intracellular domain of the receptors. This activates a specific signal cascade inside the cell, resulting in cell differentiation, cell survival, and/or cell proliferation. As can be seen in the graphic above, the TrkA receptor is activated by Nerve Growth Factor (NGF), the TrkB receptor is activated by Brain-Derived Growth Factor (BDNF) or NT4/5, and the TrkC receptor is activated by NT3. In development under normal conditions, when the Trk receptor binds to its specific NT ligand, different signal pathways within the cell are activated (see graphic above). When TrkA binds NGF, the Ras/MAP kinase pathway is activated, along with PLC gamma and PI3K, which leads to cell proliferation. When TrkB binds BDNF, the Ras-ERK pathway is activated, as well as activating the PI3K and PLC gamma pathways, leading to neuronal cell differentiation and survival. When TrkC binds NT3, the PI3 and AKT pathways are activated, insuring cell survival. The regulation of each of these receptors is critical to normal neuronal development. In cancer, Trk receptors are dysregulated due to one of several genetic alterations that prevent the normal regulation of the signals controlled by the receptors. The most clinically relevant genetic alteration that has been found in the Trk receptors in cancer is called a gene fusion, where a portion of the NTRK gene encoding the Trk receptor has broken from the rest of the gene, and has become attached to a portion of another gene. In the case of gene fusions with Trk receptors, the fusion Trk proteins no longer require their specific ligand to activate signal pathways within the cell, but instead are continually activated. They have lost their normal negative regulation, and send constant proliferation signals to the cell, promoting cancer growth and survival. Other genetic alterations in NTRK genes that have been found in cancers include mutations, in-frame deletions of the gene, and alternative splicing. Both in-frame deletions and alternative splicing result in a Trk receptor that is missing specific regions of the protein. Many different NTRK gene fusions have been identified in tumors. Recently, drug companies have developed multiple Trk inhibitors as possible treatments for aberrant Trk proteins in cancer. Some of these Trk inhibitors are currently in clinical trials at MGH and at other cancer centers. Additional Trk inhibitors are also under development by pharmaceutical companies, and will soon be in patient clinical trials. More studies are needed to determine which Trk inhibitors are the most effective against specific NTRK genetic alterations in specific tumors. Graphic was adapted from the article, NTRK gene fusions as novel targets of cancer therapy across multiple tumour types. Authors: Alessio Amatu, Andrea Sartore-Bianchi, and Salvatore Siena. ESMO Open 2016:1e000023.
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The Tropomyosin receptor kinase (Trk) family has three members, Trk A, Trk B, and Trk C. They are encoded by three separate genes, NTRK1, NTRK2, and NTRK 3, respectively. Each has an external domain outside the cell membrane that can bind ligand, a transmembrane domain that traverses the cell membrane, and an intracellular domain that transmits the signal if ligand-binding occurs. The normal function of these tyrosine kinase cell surface receptors is on neuronal cells, where they have important roles in the development and activity of the nervous system.
TrkA, TrkB and TrkC are each activated by a different neurotrophin (NT) ligand, and when stimulated by the appropriate NT ligand, multiple single receptors cluster together and phosphates are added to the intracellular domain of the receptors. This activates a specific signal cascade inside the cell, resulting in cell differentiation, cell survival, and/or cell proliferation. As can be seen in the graphic above, the TrkA receptor is activated by Nerve Growth Factor (NGF), the TrkB receptor is activated by Brain-Derived Growth Factor (BDNF) or NT4/5, and the TrkC receptor is activated by NT3.
In development under normal conditions, when the Trk receptor binds to its specific NT ligand, different signal pathways within the cell are activated (see graphic above). When TrkA binds NGF, the Ras/MAP kinase pathway is activated, along with PLC gamma and PI3K, which leads to cell proliferation. When TrkB binds BDNF, the Ras-ERK pathway is activated, as well as activating the PI3K and PLC gamma pathways, leading to neuronal cell differentiation and survival. When TrkC binds NT3, the PI3 and AKT pathways are activated, insuring cell survival. The regulation of each of these receptors is critical to normal neuronal development.
In cancer, Trk receptors are dysregulated due to one of several genetic alterations that prevent the normal regulation of the signals controlled by the receptors. The most clinically relevant genetic alteration that has been found in the Trk receptors in cancer is called a gene fusion, where a portion of the NTRK gene encoding the Trk receptor has broken from the rest of the gene, and has become attached to a portion of another gene. In the case of gene fusions with Trk receptors, the fusion Trk proteins no longer require their specific ligand to activate signal pathways within the cell, but instead are continually activated. They have lost their normal negative regulation, and send constant proliferation signals to the cell, promoting cancer growth and survival. Other genetic alterations in NTRK genes that have been found in cancers include mutations, in-frame deletions of the gene, and alternative splicing. Both in-frame deletions and alternative splicing result in a Trk receptor that is missing specific regions of the protein.
Many different NTRK gene fusions have been identified in tumors. Recently, drug companies have developed multiple Trk inhibitors as possible treatments for aberrant Trk proteins in cancer. Some of these Trk inhibitors are currently in clinical trials at MGH and at other cancer centers. Additional Trk inhibitors are also under development by pharmaceutical companies, and will soon be in patient clinical trials. More studies are needed to determine which Trk inhibitors are the most effective against specific NTRK genetic alterations in specific tumors.
Graphic was adapted from the article, NTRK gene fusions as novel targets of cancer therapy across multiple tumour types. Authors: Alessio Amatu, Andrea Sartore-Bianchi, and Salvatore Siena. ESMO Open 2016:1e000023.
The Tropomyosin receptor kinase (Trk) family has three members, Trk A, Trk B, and Trk C. They are encoded by three separate genes, NTRK1, NTRK2, and NTRK 3, respectively. Each has an external domain outside the cell membrane that can bind ligand, a transmembrane domain that traverses the cell membrane, and an intracellular domain that transmits the signal if ligand-binding occurs. The normal function of these tyrosine kinase cell surface receptors is on neuronal cells, where they have important roles in the development and activity of the nervous system.
TrkA, TrkB and TrkC are each activated by a different neurotrophin (NT) ligand, and when stimulated by the appropriate NT ligand, multiple single receptors cluster together and phosphates are added to the intracellular domain of the receptors. This activates a specific signal cascade inside the cell, resulting in cell differentiation, cell survival, and/or cell proliferation. As can be seen in the graphic above, the TrkA receptor is activated by Nerve Growth Factor (NGF), the TrkB receptor is activated by Brain-Derived Growth Factor (BDNF) or NT4/5, and the TrkC receptor is activated by NT3.
In development under normal conditions, when the Trk receptor binds to its specific NT ligand, different signal pathways within the cell are activated (see graphic above). When TrkA binds NGF, the Ras/MAP kinase pathway is activated, along with PLC gamma and PI3K, which leads to cell proliferation. When TrkB binds BDNF, the Ras-ERK pathway is activated, as well as activating the PI3K and PLC gamma pathways, leading to neuronal cell differentiation and survival. When TrkC binds NT3, the PI3 and AKT pathways are activated, insuring cell survival. The regulation of each of these receptors is critical to normal neuronal development.
In cancer, Trk receptors are dysregulated due to one of several genetic alterations that prevent the normal regulation of the signals controlled by the receptors. The most clinically relevant genetic alteration that has been found in the Trk receptors in cancer is called a gene fusion, where a portion of the NTRK gene encoding the Trk receptor has broken from the rest of the gene, and has become attached to a portion of another gene. In the case of gene fusions with Trk receptors, the fusion Trk proteins no longer require their specific ligand to activate signal pathways within the cell, but instead are continually activated. They have lost their normal negative regulation, and send constant proliferation signals to the cell, promoting cancer growth and survival. Other genetic alterations in NTRK genes that have been found in cancers include mutations, in-frame deletions of the gene, and alternative splicing. Both in-frame deletions and alternative splicing result in a Trk receptor that is missing specific regions of the protein.
Many different NTRK gene fusions have been identified in tumors. Recently, drug companies have developed multiple Trk inhibitors as possible treatments for aberrant Trk proteins in cancer. Some of these Trk inhibitors are currently in clinical trials at MGH and at other cancer centers. Additional Trk inhibitors are also under development by pharmaceutical companies, and will soon be in patient clinical trials. More studies are needed to determine which Trk inhibitors are the most effective against specific NTRK genetic alterations in specific tumors.
Graphic was adapted from the article, NTRK gene fusions as novel targets of cancer therapy across multiple tumour types. Authors: Alessio Amatu, Andrea Sartore-Bianchi, and Salvatore Siena. ESMO Open 2016:1e000023.
Expand Collapse in-frame deletion  in TRK 1,2,3
In-frame deletions are genetic alterations of genes that result in segments of the gene being missing. This results in the translation of an abnormal protein that is not correct structurally, and cannot be regulated normally in cells.
In-frame deletions are genetic alterations of genes that result in segments of the gene being missing. This results in the translation of an abnormal protein that is not correct structurally, and cannot be regulated normally in cells.

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Your Matched Clinical Trials

Trial Matches: (G) - Gene, (M) - Mutation
Trial Status: Showing all 5 results Per Page:
Protocol # Title Location Status Match
NCT02279433 A First-in-human Study to Evaluate the Safety, Tolerability and Pharmacokinetics of DS-6051b A First-in-human Study to Evaluate the Safety, Tolerability and Pharmacokinetics of DS-6051b MGH Open GM
NCT02228811 A Study of DCC-2701 in Participants With Advanced Solid Tumors A Study of DCC-2701 in Participants With Advanced Solid Tumors MGH Open GM
NCT02219711 Phase 1/1b Study of MGCD516 in Patients With Advanced Cancer Phase 1/1b Study of MGCD516 in Patients With Advanced Cancer MGH Open GM
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 G
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 G
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.
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