Gastric/Esophageal, TRK 1,2,3

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Expand Collapse Gastric/Esophageal  - General Description Cancers of the stomach and esophagus, can also collectively be referred to as gastroesophageal or esophagogastric cancer. Gastric cancer incidence varies throughout the world, with a higher frequency in some countries-perhaps due to different diets or other factors. Esophageal cancers are more common in men than in women. Both alcohol use and tobacco use are associated with a higher risk of developing gastric or esophageal cancer. According to the National Cancer Institute (NCI) data, 16,940 men and 15,690 women were projected to be diagnosed with gastric cancer in the United States in 2017.

Most cancers involving the esophagus or stomach are either squamous cell cancer (SCC) or adenocarcinoma. Gastric and esophageal cancers tend to develop slowly over many years in the inner mucosal layer of the stomach or esophagus. These early changes rarely cause symptoms, and therefore frequently go undetected. As esophageal and gastric cancers become more advanced, symptoms become more apparent. Once symptoms bring a patient to a doctor for medical attention, the diagnosis can be made. Thorough diagnostics are available at the MGH, initially involving an endoscopic biopsy, which is used to definitively diagnose the cancer by experienced Pathologists. Subsequent to a confirmed diagnosis, it is important to stage the cancer which includes in-depth pathology analysis, as well as a radiographic imaging procedure such as CT or PET scan. Often lymph nodes near the cancer are analysed to insure the cancer has not spread.

There has been a growing interest in the molecular features of esophageal and gastric cancers, as genetic alterations in these cancers have been identified in patients. Some genes that have been found to be involved in these two cancer types are mutations or amplification of the genes that encode HER2, MET or EGFR. Other genetic alterations have also been identified. Testing for these genetic alterations is performed in the genetics lab of the MGH, enabling physicians to utilize targeted therapies tailored for individual tumors. Treatment options for esophageal and gastric cancers are available at the MGH Cancer Center, as well as Clinical Trials testing new treatments for patients with this diagnosis.

Source: National Cancer Institute, 2018
Cancers of the stomach and esophagus, can also collectively be referred to as gastroesophageal or esophagogastric cancer. Gastric cancer incidence varies throughout the world, with a higher frequency in some countries-perhaps due to different diets or other factors. Esophageal cancers are more common in men than in women. Both alcohol use and tobacco use are associated with a higher risk of developing gastric or esophageal cancer. According to the National Cancer Institute (NCI) data, 16,940 men and 15,690 women were projected to be diagnosed with gastric cancer in the United States in 2017.

Most cancers involving the esophagus or stomach are either squamous cell cancer (SCC) or adenocarcinoma. Gastric and esophageal cancers tend to develop slowly over many years in the inner mucosal layer of the stomach or esophagus. These early changes rarely cause symptoms, and therefore frequently go undetected. As esophageal and gastric cancers become more advanced, symptoms become more apparent. Once symptoms bring a patient to a doctor for medical attention, the diagnosis can be made. Thorough diagnostics are available at the MGH, initially involving an endoscopic biopsy, which is used to definitively diagnose the cancer by experienced Pathologists. Subsequent to a confirmed diagnosis, it is important to stage the cancer which includes in-depth pathology analysis, as well as a radiographic imaging procedure such as CT or PET scan. Often lymph nodes near the cancer are analysed to insure the cancer has not spread.

There has been a growing interest in the molecular features of esophageal and gastric cancers, as genetic alterations in these cancers have been identified in patients. Some genes that have been found to be involved in these two cancer types are mutations or amplification of the genes that encode HER2, MET or EGFR. Other genetic alterations have also been identified. Testing for these genetic alterations is performed in the genetics lab of the MGH, enabling physicians to utilize targeted therapies tailored for individual tumors. Treatment options for esophageal and gastric cancers are available at the MGH Cancer Center, as well as Clinical Trials testing new treatments for patients with this diagnosis.

Source: National Cancer Institute, 2018
Cancers of the stomach and esophagus, can also collectively be referred to as gastroesophageal or esophagogastric cancer. Gastric cancer incidence varies throughout the world, with a higher frequency in some countries-perhaps due to different diets or other factors. Esophageal cancers are more common in men than in women. Both alcohol use and tobacco use are associated with a higher risk of developing gastric or esophageal cancer. According to the National Cancer Institute (NCI) data, 16,940 men and 15,690 women were projected to be diagnosed with gastric cancer in the United States in 2017.

Most cancers involving the esophagus or stomach are either squamous cell cancer (SCC) or adenocarcinoma. Gastric and esophageal cancers tend to develop slowly over many years in the inner mucosal layer of the stomach or esophagus. These early changes rarely cause symptoms, and therefore frequently go undetected. As esophageal and gastric cancers become more advanced, symptoms become more apparent. Once symptoms bring a patient to a doctor for medical attention, the diagnosis can be made. Thorough diagnostics are available at the MGH, initially involving an endoscopic biopsy, which is used to definitively diagnose the cancer by experienced Pathologists. Subsequent to a confirmed diagnosis, it is important to stage the cancer which includes in-depth pathology analysis, as well as a radiographic imaging procedure such as CT or PET scan. Often lymph nodes near the cancer are analysed to insure the cancer has not spread.

There has been a growing interest in the molecular features of esophageal and gastric cancers, as genetic alterations in these cancers have been identified in patients. Some genes that have been found to be involved in these two cancer types are mutations or amplification of the genes that encode HER2, MET or EGFR. Other genetic alterations have also been identified. Testing for these genetic alterations is performed in the genetics lab of the MGH, enabling physicians to utilize targeted therapies tailored for individual tumors. Treatment options for esophageal and gastric cancers are available at the MGH Cancer Center, as well as Clinical Trials testing new treatments for patients with this diagnosis.

Source: National Cancer Institute, 2018
Cancers of the stomach and esophagus, can also collectively be referred to as gastroesophageal or esophagogastric cancer. Gastric cancer incidence varies throughout the world, with a higher frequency in some countries-perhaps due to different diets or other factors. Esophageal cancers are more common in men than in women. Both alcohol use and tobacco use are associated with a higher risk of developing gastric or esophageal cancer. According to the National Cancer Institute (NCI) data, 16,940 men and 15,690 women were projected to be diagnosed with gastric cancer in the United States in 2017.

Most cancers involving the esophagus or stomach are either squamous cell cancer (SCC) or adenocarcinoma. Gastric and esophageal cancers tend to develop slowly over many years in the inner mucosal layer of the stomach or esophagus. These early changes rarely cause symptoms, and therefore frequently go undetected. As esophageal and gastric cancers become more advanced, symptoms become more apparent. Once symptoms bring a patient to a doctor for medical attention, the diagnosis can be made. Thorough diagnostics are available at the MGH, initially involving an endoscopic biopsy, which is used to definitively diagnose the cancer by experienced Pathologists. Subsequent to a confirmed diagnosis, it is important to stage the cancer which includes in-depth pathology analysis, as well as a radiographic imaging procedure such as CT or PET scan. Often lymph nodes near the cancer are analysed to insure the cancer has not spread.

There has been a growing interest in the molecular features of esophageal and gastric cancers, as genetic alterations in these cancers have been identified in patients. Some genes that have been found to be involved in these two cancer types are mutations or amplification of the genes that encode HER2, MET or EGFR. Other genetic alterations have also been identified. Testing for these genetic alterations is performed in the genetics lab of the MGH, enabling physicians to utilize targeted therapies tailored for individual tumors. Treatment options for esophageal and gastric cancers are available at the MGH Cancer Center, as well as Clinical Trials testing new treatments for patients with this diagnosis.

Source: National Cancer Institute, 2018
Expand Collapse TRK 1,2,3  - General Description
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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 TRK 1,2,3  in Gastric/Esophageal
Genetic alterations in TRK family members have been found in gastric and esophageal cancers. The most common alteration in TRK is a fusion protein, a part of the TRK gene inserted in a portion of a gene encoding another protein, resulting in a "fusion" protein. These abnormal proteins are made up of 1 part TRK, and a portion of the protein of the gene that TRK inserted itself into. These are not normal TRK proteins, and cannot be regulated normally. These TRK fusions send growth and proliferation signals constantly, and contribute to the development of cancer.

Testing for genetic alterations in TRK genes is performed at MGH in its highly sophisticated genetic lab. Treatment and clinical trials studying new TRK inhibitors are also available at MGH.

Genetic alterations in TRK family members have been found in gastric and esophageal cancers. The most common alteration in TRK is a fusion protein, a part of the TRK gene inserted in a portion of a gene encoding another protein, resulting in a "fusion" protein. These abnormal proteins are made up of 1 part TRK, and a portion of the protein of the gene that TRK inserted itself into. These are not normal TRK proteins, and cannot be regulated normally. These TRK fusions send growth and proliferation signals constantly, and contribute to the development of cancer.

Testing for genetic alterations in TRK genes is performed at MGH in its highly sophisticated genetic lab. Treatment and clinical trials studying new TRK inhibitors are also available at MGH.

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 Results: 1-10 of 23 Per Page:
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Protocol # Title Location Status Match
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 DG
NCT02099058 A Phase 1/1b Study With ABBV-399, an Antibody Drug Conjugate, in Subjects With Advanced Solid Cancer Tumors A Phase 1/1b Study With ABBV-399, an Antibody Drug Conjugate, in Subjects With Advanced Solid Cancer Tumors MGH Open D
NCT02908451 A Study of AbGn-107 in Patients With Gastric, Colorectal, or Pancreatic Cancer A Study of AbGn-107 in Patients With Gastric, Colorectal, or Pancreatic Cancer MGH Open D
NCT02880371 A Study of ARRY-382 in Combination With Pembrolizumab for the Treatment of Patients With Advanced Solid Tumors A Study of ARRY-382 in Combination With Pembrolizumab for the Treatment of Patients With Advanced Solid Tumors MGH Open D
NCT02467361 A Study of BBI608 Administered in Combination With Immune Checkpoint Inhibitors in Adult Patients With Advanced Cancers A Study of BBI608 Administered in Combination With Immune Checkpoint Inhibitors in Adult Patients With Advanced Cancers MGH Open D
NCT01325441 A Study of BBI608 Administered With Paclitaxel in Adult Patients With Advanced Malignancies A Study of BBI608 Administered With Paclitaxel in Adult Patients With Advanced Malignancies MGH Open D
NCT02013154 A Study of DKN-01 in Combination With Paclitaxel or Pembrolizumab A Study of DKN-01 in Combination With Paclitaxel or Pembrolizumab MGH Open D
NCT02715531 A Study of the Safety and Efficacy of Atezolizumab Administered in Combination With Bevacizumab and/or Other Treatments in Participants With Solid Tumors A Study of the Safety and Efficacy of Atezolizumab Administered in Combination With Bevacizumab and/or Other Treatments in Participants With Solid Tumors MGH Open D
NCT02743494 An Investigational Immuno-therapy Study of Nivolumab or Placebo in Patients With Resected Esophageal or Gastroesophageal Junction Cancer An Investigational Immuno-therapy Study of Nivolumab or Placebo in Patients With Resected Esophageal or Gastroesophageal Junction Cancer MGH Open D
NCT02488759 An Investigational Immuno-therapy Study to Investigate the Safety and Effectiveness of Nivolumab, and Nivolumab Combination Therapy in Virus-associated Tumors An Investigational Immuno-therapy Study to Investigate the Safety and Effectiveness of Nivolumab, and Nivolumab Combination Therapy in Virus-associated Tumors MGH Open D
Trial Status: Showing Results: 1-10 of 23 Per Page:
123Next »

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