Gastric/Esophageal, EGFR, Activating Mutations

View:
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 EGFR  - General Description
CLICK IMAGE FOR MORE INFORMATION
The EGFR gene encodes for a cell-surface protein known as the epidermal growth factor receptor, which is found in many normal epithelial tissues such as the skin and hair follicles. When epidermal growth factor ligand bind to EGFR, they activate several different cell signaling pathways that control various cell functions, including cell growth and proliferation.

Mutations in EGFR can lead to unregulated activation of the protein. These types of activating mutations are often found in NSCLC (non-small cell lung cancer), glioblastoma and head and neck squamous cell carcinoma. Sometimes, excess EGFR protein is produced due to the presence of too many copies of the EGFR gene, leading to excessive cell division and growth in the presence of epidermal growth factor. Among the human cancers in which EGFR overabundance is present are cancers of the head and neck (squamous cell), colon, rectum, lung (NSCLC), central nervous system (glioblastoma), pancreas and breast (HER2-positive metastatic). Blocking EGFR in tumors may keep cancer cells from growing. The FDA has approved several therapies that target EGFR in one or more cancers. Testing for genetic alterations of EGFR is available at the MGH genetics lab. Treatment for EGFR-mutant tumors, along with clinical trials testing new drugs for the treatment of EGFR-mutant tumors are available at the MGH Cancer Center.

Tumor mutation profiling performed clinically at the MGH Cancer Center has indicated that EGFR mutations occur primarily in lung cancer (~15%), but also in a minor subset of gastric (2%), brain (1%) and pancreatic (1%) cancers.

Source: Genetics Home Reference
The EGFR gene encodes for a cell-surface protein known as the epidermal growth factor receptor, which is found in many normal epithelial tissues such as the skin and hair follicles. When epidermal growth factor ligand bind to EGFR, they activate several different cell signaling pathways that control various cell functions, including cell growth and proliferation.

Mutations in EGFR can lead to unregulated activation of the protein. These types of activating mutations are often found in NSCLC (non-small cell lung cancer), glioblastoma and head and neck squamous cell carcinoma. Sometimes, excess EGFR protein is produced due to the presence of too many copies of the EGFR gene, leading to excessive cell division and growth in the presence of epidermal growth factor. Among the human cancers in which EGFR overabundance is present are cancers of the head and neck (squamous cell), colon, rectum, lung (NSCLC), central nervous system (glioblastoma), pancreas and breast (HER2-positive metastatic). Blocking EGFR in tumors may keep cancer cells from growing. The FDA has approved several therapies that target EGFR in one or more cancers. Testing for genetic alterations of EGFR is available at the MGH genetics lab. Treatment for EGFR-mutant tumors, along with clinical trials testing new drugs for the treatment of EGFR-mutant tumors are available at the MGH Cancer Center.

Tumor mutation profiling performed clinically at the MGH Cancer Center has indicated that EGFR mutations occur primarily in lung cancer (~15%), but also in a minor subset of gastric (2%), brain (1%) and pancreatic (1%) cancers.

Source: Genetics Home Reference
PubMed ID's
15864276, 15118073, 15118125, 15329413, 18772890, 15837736, 16720329, 21057220
Expand Collapse Activating Mutations  in EGFR
All of the genetic alterations in EGFR found in cancers are considered activating mutations. These changes, including genetic mutations or amplification, change the EGF receptor into one that is constantly sending signals to the cell to grow, even in the absence of growth signal molecules (called ligands) binding to the receptor. Other types of genetic alterations in EGFR that are associated with cancers can cause overproduction of the receptor (amplification), also creating EGFR receptors that are constitutively (constantly) activated, and not subject to normal regulation.
All of the genetic alterations in EGFR found in cancers are considered activating mutations. These changes, including genetic mutations or amplification, change the EGF receptor into one that is constantly sending signals to the cell to grow, even in the absence of growth signal molecules (called ligands) binding to the receptor. Other types of genetic alterations in EGFR that are associated with cancers can cause overproduction of the receptor (amplification), also creating EGFR receptors that are constitutively (constantly) activated, and not subject to normal regulation.

Genetic alterations in the EGFR gene have been found in some gastric and esophageal cancers. These mutations in the EGFR gene result in the production of an abnormal protein, one that cannot be regulated in the normal way by the cell. EGFR is normally activated by the binding of a ligand to the EGF receptor, causing it to trigger signals to the cell to grow and proliferate. However, the mutated protein is constantly activated, even when no ligand has bound to the receptor. These constant signals to the cell to grow and proliferate can contribute to the development of cancer.

Genetic alterations in the EGFR gene have been found in some gastric and esophageal cancers. These mutations in the EGFR gene result in the production of an abnormal protein, one that cannot be regulated in the normal way by the cell. EGFR is normally activated by the binding of a ligand to the EGF receptor, causing it to trigger signals to the cell to grow and proliferate. However, the mutated protein is constantly activated, even when no ligand has bound to the receptor. These constant signals to the cell to grow and proliferate can contribute to the development of cancer.

Share with your Physican

Print information for your Physician.

Print information

Your Matched Clinical Trials

Trial Matches: (D) - Disease, (G) - Gene, (M) - Mutation
Trial Status: Showing Results: 1-10 of 24 Per Page:
123Next »
Protocol # Title Location Status Match
NCT01953926 Neratinib HER Mutation Basket Study (SUMMIT) Neratinib HER Mutation Basket Study (SUMMIT) MGH Open DG
NCT02500199 Phase I Study of Pyrotinib in Patients With HER2-positive Solid Tumors Phase I Study of Pyrotinib in Patients With HER2-positive Solid Tumors MGH Open DG
NCT02099058 A Study Evaluating the Safety, Pharmacokinetics (PK), and Preliminary Efficacy of ABBV-399 in Subjects With Advanced Solid Tumors. A Study Evaluating the Safety, Pharmacokinetics (PK), and Preliminary Efficacy of ABBV-399 in Subjects With Advanced Solid 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
NCT03013218 A Study of ALX148 in Patients With Advanced Solid Tumors and Lymphoma A Study of ALX148 in Patients With Advanced Solid Tumors and Lymphoma 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
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
Trial Status: Showing Results: 1-10 of 24 Per Page:
123Next »

Share with your Physican

Print information for your Physician.

Print information