Gastric/Esophageal, APC

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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 APC  - General Description
CLICK IMAGE FOR MORE INFORMATION
Adenomatous Polyposis Coli (APC) is a regulator of several fundamental cellular processes, including cell division, cell attachment, cell migration, cell polarization, and chromosome segregation during division. In these complex functions, APC activity is essential for the prevention of cancer (in other words, APC acts as a tumor suppressor). APC is involved in these cellular functions through interactions with other cellular proteins. One of the most recognized functions of APC is in regulating levels of beta-catenin, which is part of the WNT signal pathway in cells.

The WNT signal pathway is important in a variety of cellular processes. In the left hand cell in the graphic above, one can see that when there is no WNT ligand to bind to the extracellular WNT receptor, APC exists in a complex with other proteins. The complex is known as the “destruction complex”, and acts to destroy beta-catenin in the cell cytoplasm. This keeps levels of beta-catenin in the cell very low. Beta-catenin also binds to E-cadherin at the cell membrane, and is involved in cell to cell contacts (see graphic).

When WNT ligand binds to the extracellular WNT receptor, as is depicted in the right hand cell in the graphic above, it activates the receptor to send a signal that causes the dissociation of the destruction complex including APC. Without the destruction complex, beta-catenin builds up in the cytoplasm of the cells. In the cytoplasm, beta-catenin binds to T-cell factor (TCF), and together they translocate into the nucleus. They then bind to DNA and activate the transcription of genes that promote cell growth, such as c-Myc and cyclin D1. In the presence of WNT ligand binding, normal cells proliferate and divide.

In some cancers, APC is genetically altered, either through mutation or actual loss of the gene. Mutations in APC have been found in most colon cancers, whether familial (inherited genetic alterations) or spontaneous (somatic gene mutation). Mutations in APC have also been found in other cancers, including in adenocarcinoma of the lung. When APC is missing or mutated it cannot function in the destruction complex, and beta-catenin builds up in the cytoplasm even in the absence of WNT signaling. This unregulated high level of beta-catenin binds to TCF, moves into the nucleus of cancer cells, and binds to DNA to stimulate transcription of c-Myc and cyclin D1, causing cells to grow and divide.

Another way that APC function can be disrupted is through changes in E-cadherin, a protein that binds to beta-catenin, and mediates cell to cell contact (see graphic above). In many cancers, E-cadherin expression is lost, and without E-cadherin interacting with beta-catenin, cell to cell contact becomes dysregulated. Other genetic changes in E-cadherin can be inherited. The gene that encodes E-cadherin is called CDH1. Inherited germline mutations in CDH1 result in an E-cadherin protein that does not function normally, and these inherited mutations in CDH1/E-cadherin have been found to be associated with Hereditary Diffuse Gastric cancer/Lobular Breast Cancer Syndrome. The fact that so many genetic alterations in the pathways associated with APC highlight the importance of the APC tumor suppressor in normally preventing cancer.


Sources:
Graphic adapted from slideshareecdn.com 02-cat-neoplasia-5081/95/02-cat-neoplasia-14-728.jpg?cb=124463107
Valeria Bugos, Camila Guezada, Nicolas Briceno
Text sources PMID#17881494 Adenomatous polyposis coli (APC): a multi-functional tumor suppressor gene

Adenomatous Polyposis Coli (APC) is a regulator of several fundamental cellular processes, including cell division, cell attachment, cell migration, cell polarization, and chromosome segregation during division. In these complex functions, APC activity is essential for the prevention of cancer (in other words, APC acts as a tumor suppressor). APC is involved in these cellular functions through interactions with other cellular proteins. One of the most recognized functions of APC is in regulating levels of beta-catenin, which is part of the WNT signal pathway in cells.

The WNT signal pathway is important in a variety of cellular processes. In the left hand cell in the graphic above, one can see that when there is no WNT ligand to bind to the extracellular WNT receptor, APC exists in a complex with other proteins. The complex is known as the “destruction complex”, and acts to destroy beta-catenin in the cell cytoplasm. This keeps levels of beta-catenin in the cell very low. Beta-catenin also binds to E-cadherin at the cell membrane, and is involved in cell to cell contacts (see graphic).

When WNT ligand binds to the extracellular WNT receptor, as is depicted in the right hand cell in the graphic above, it activates the receptor to send a signal that causes the dissociation of the destruction complex including APC. Without the destruction complex, beta-catenin builds up in the cytoplasm of the cells. In the cytoplasm, beta-catenin binds to T-cell factor (TCF), and together they translocate into the nucleus. They then bind to DNA and activate the transcription of genes that promote cell growth, such as c-Myc and cyclin D1. In the presence of WNT ligand binding, normal cells proliferate and divide.

In some cancers, APC is genetically altered, either through mutation or actual loss of the gene. Mutations in APC have been found in most colon cancers, whether familial (inherited genetic alterations) or spontaneous (somatic gene mutation). Mutations in APC have also been found in other cancers, including in adenocarcinoma of the lung. When APC is missing or mutated it cannot function in the destruction complex, and beta-catenin builds up in the cytoplasm even in the absence of WNT signaling. This unregulated high level of beta-catenin binds to TCF, moves into the nucleus of cancer cells, and binds to DNA to stimulate transcription of c-Myc and cyclin D1, causing cells to grow and divide.

Another way that APC function can be disrupted is through changes in E-cadherin, a protein that binds to beta-catenin, and mediates cell to cell contact (see graphic above). In many cancers, E-cadherin expression is lost, and without E-cadherin interacting with beta-catenin, cell to cell contact becomes dysregulated. Other genetic changes in E-cadherin can be inherited. The gene that encodes E-cadherin is called CDH1. Inherited germline mutations in CDH1 result in an E-cadherin protein that does not function normally, and these inherited mutations in CDH1/E-cadherin have been found to be associated with Hereditary Diffuse Gastric cancer/Lobular Breast Cancer Syndrome. The fact that so many genetic alterations in the pathways associated with APC highlight the importance of the APC tumor suppressor in normally preventing cancer.


Sources:
Graphic adapted from slideshareecdn.com 02-cat-neoplasia-5081/95/02-cat-neoplasia-14-728.jpg?cb=124463107
Valeria Bugos, Camila Guezada, Nicolas Briceno
Text sources PMID#17881494 Adenomatous polyposis coli (APC): a multi-functional tumor suppressor gene

PubMed ID's
1788494
Expand Collapse APC  in Gastric/Esophageal
Genetic alterations in the APC gene have been found in gastric and esophageal cancers. These various genetic alterations result in an altered APC protein, which cannot be regulated normally in the cell. Abnormal APC can result in the development of cancer.

Genetic alterations in the APC gene have been found in gastric and esophageal cancers. These various genetic alterations result in an altered APC protein, which cannot be regulated normally in the cell. Abnormal APC can result in the development of cancer.

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 26 Per Page:
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Protocol # Title Location Status Match
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
NCT02482441 A Phase 1a/b Dose Escalation Study of the Safety, Pharmacokinetics, and Pharmacodynamics of OMP-131R10 A Phase 1a/b Dose Escalation Study of the Safety, Pharmacokinetics, and Pharmacodynamics of OMP-131R10 MGH Open D
NCT03279237 A Pilot Study of FOLFIRINOX in Combination With Neoadjuvant Radiation for Gastric and GE Junction Cancers A Pilot Study of FOLFIRINOX in Combination With Neoadjuvant Radiation for Gastric and GE Junction Cancers 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
NCT02323191 A Study of Emactuzumab and Atezolimumab Administered in Combination in Participants With Advanced Solid Tumors A Study of Emactuzumab and Atezolimumab Administered in Combination in Participants With Advanced Solid Tumors MGH Open D
NCT02715531 A Study of the Safety and Tolerability of Atezolizumab Administered in Combination With Bevacizumab and/or Other Treatments in Participants With Solid Tumors A Study of the Safety and Tolerability 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
Trial Status: Showing Results: 1-10 of 26 Per Page:
123Next »

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