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Expand Collapse Lung Cancer  - General Description This year about 226,000 people in the U.S. will be told by a doctor that they have lung cancer. However, about 390,000 Americans remain alive today after having been diagnosed with this malignancy. Lung cancer includes tumors that begin in tissues lining air passages inside the lungs and bronchi. The bronchi are the 2 branches of the windpipe (trachea) that lead to the lungs. Based on how the cells look under a microscope, lung cancers are divided into 2 main types: small cell lung cancer (SCLC) and non-small cell lung cancer (NSCLC). NSCLC accounts for 85% of these cases.

The main subtypes of NSCLC are squamous cell carcinoma (cancer beginning in thin, flat scaly-looking cells), adenocarcinoma (cancer beginning in cells that make mucus and other substances) and large cell carcinoma (cancer beginning in several types of large cells). The 2 main types of SCLC are small cell carcinoma (oat cell cancer) and combined small cell carcinoma.

Lung cancer (and other tumors) can spread (metastasize) from the place where it started (the primary tumor) in 3 ways. First, it can invade the normal tissue surrounding it. Second, cancer cells can enter the lymph system and travel through lymph vessels to distant parts of the body. Third, the cancer cells can get into the bloodstream and go to other places in the body. In these distant places, the cancer cells cause secondary tumors to grow. The main sites to which lung cancer spreads are the adrenal gland, liver and lungs.

To find out whether the cancer has entered the lymph system, a surgeon removes all or part of a node near the primary tumor and a pathologist looks at it through a microscope to see if cancer cells are present. Several kinds of imaging also can be performed to determine if the cancer has spread. These include MRI, bone scans and endoscopic ultrasound (EUS).

The FDA has approved several targeted therapies to treat patients with NSCLC. These include bevacizumab (Avastin), cetuximab (Erbitux), erlotinib (Tarceva), gefitnib (Iressa) and crizotinib (Xalkori). So far there are no FDA-approved targeted therapies for SCLC.

Despite significant improvements in the treatment of lung cancers, novel therapies and treatment strategies are needed.

Source: National Cancer Institute, 2012
Estimated new cases and deaths from lung cancer (non-small cell and small cell combined) in the United States in 2012:

New cases: 226,160
Deaths: 160,340

Lung cancer is the leading cause of cancer-related mortality in the United States. The 5-year relative survival rate from 1995 to 2001 for patients with lung cancer was 15.7%. The 5-year relative survival rate varies markedly depending on the stage at diagnosis, from 49% to 16% to 2% for patients with local, regional and distant stage disease, respectively.

NSCLC arises from the epithelial cells of the lung, from the central bronchi to the terminal alveoli. The histological type of NSCLC correlates with the site of origin, reflecting the variation in respiratory tract epithelium from the bronchi to the alveoli. Squamous cell carcinoma usually starts near a central bronchus while adenocarcinoma usually originates in peripheral lung tissue.

Tobacco smoking is the strongest risk factor for developing lung cancer, though it should be noted that the majority of patients diagnosed with lung cancer quit smoking years prior to diagnosis or were never-smokers (up to 15% of cases).

The identification of driver oncogene mutations in lung cancer has led to the development of targeted therapy that has vastly broadened treatment options and improved outcomes for subsets of patients with metastatic disease. It is now common practice to determine the genotype of a NSCLC patient early in the course of their diagnosis, to ensure that all possible treatment options are considered.

Source: National Cancer Institute, 2012
This year about 226,000 people in the U.S. will be told by a doctor that they have lung cancer. However, about 390,000 Americans remain alive today after having been diagnosed with this malignancy. Lung cancer includes tumors that begin in tissues lining air passages inside the lungs and bronchi. The bronchi are the 2 branches of the windpipe (trachea) that lead to the lungs. Based on how the cells look under a microscope, lung cancers are divided into 2 main types: small cell lung cancer (SCLC) and non-small cell lung cancer (NSCLC). NSCLC accounts for 85% of these cases.

The main subtypes of NSCLC are squamous cell carcinoma (cancer beginning in thin, flat scaly-looking cells), adenocarcinoma (cancer beginning in cells that make mucus and other substances) and large cell carcinoma (cancer beginning in several types of large cells). The 2 main types of SCLC are small cell carcinoma (oat cell cancer) and combined small cell carcinoma.

Lung cancer (and other tumors) can spread (metastasize) from the place where it started (the primary tumor) in 3 ways. First, it can invade the normal tissue surrounding it. Second, cancer cells can enter the lymph system and travel through lymph vessels to distant parts of the body. Third, the cancer cells can get into the bloodstream and go to other places in the body. In these distant places, the cancer cells cause secondary tumors to grow. The main sites to which lung cancer spreads are the adrenal gland, liver and lungs.

To find out whether the cancer has entered the lymph system, a surgeon removes all or part of a node near the primary tumor and a pathologist looks at it through a microscope to see if cancer cells are present. Several kinds of imaging also can be performed to determine if the cancer has spread. These include MRI, bone scans and endoscopic ultrasound (EUS).

The FDA has approved several targeted therapies to treat patients with NSCLC. These include bevacizumab (Avastin), cetuximab (Erbitux), erlotinib (Tarceva), gefitnib (Iressa) and crizotinib (Xalkori). So far there are no FDA-approved targeted therapies for SCLC.

Despite significant improvements in the treatment of lung cancers, novel therapies and treatment strategies are needed.

Source: National Cancer Institute, 2012
Estimated new cases and deaths from lung cancer (non-small cell and small cell combined) in the United States in 2012:

New cases: 226,160
Deaths: 160,340

Lung cancer is the leading cause of cancer-related mortality in the United States. The 5-year relative survival rate from 1995 to 2001 for patients with lung cancer was 15.7%. The 5-year relative survival rate varies markedly depending on the stage at diagnosis, from 49% to 16% to 2% for patients with local, regional and distant stage disease, respectively.

NSCLC arises from the epithelial cells of the lung, from the central bronchi to the terminal alveoli. The histological type of NSCLC correlates with the site of origin, reflecting the variation in respiratory tract epithelium from the bronchi to the alveoli. Squamous cell carcinoma usually starts near a central bronchus while adenocarcinoma usually originates in peripheral lung tissue.

Tobacco smoking is the strongest risk factor for developing lung cancer, though it should be noted that the majority of patients diagnosed with lung cancer quit smoking years prior to diagnosis or were never-smokers (up to 15% of cases).

The identification of driver oncogene mutations in lung cancer has led to the development of targeted therapy that has vastly broadened treatment options and improved outcomes for subsets of patients with metastatic disease. It is now common practice to determine the genotype of a NSCLC patient early in the course of their diagnosis, to ensure that all possible treatment options are considered.

Source: National Cancer Institute, 2012
Expand Collapse EGFR  - General Description
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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 G719C (c.2155G>T)  in EGFR
The EGFR G719C mutation arises from the nucleotide change c.2155G>T in exon 18, resulting in an amino acid substitution of the glycine (G) at position 719 by a cysteine (C).
The EGFR G719C mutation arises from the nucleotide change c.2155G>T in exon 18, resulting in an amino acid substitution of the glycine (G) at position 719 by a cysteine (C).

EGFR mutations occur almost exclusively in adenocarcinoma and may impart a more favorable prognosis when compared to lung cancer patients whose tumor does not carry an EGFR mutation. The presence of an EGFR mutation predicts a better outcome for lung cancer patients, regardless of treatment received. These mutations are mainly found in patients with a low smoking history (incidence of 50% among U.S. non-smokers with lung cancer) and those of Asian race (incidence of up to 75% in Japanese non-smokers with lung cancer).

Currently, the FDA-approved use of erlotinib or afatinib in the treatment of metastatic non-small cell lung cancer is restricted to the presence of either an EGFR exon 19 deletion or an L858R mutation in the patient’s tumor. The safety and efficacy of these targeted agents have not been established in patients whose lung tumors carry other EGFR mutations, such as those at position G719. Clinical trials are now investigating novel inhibitors that are active across a number of ERBB family members (EGFR, HER2, HER3, HER4) and have reported increased response rates in tumors that carry even these rare EGFR mutations.

EGFR mutations occur almost exclusively in adenocarcinoma and may impart a more favorable prognosis when compared to lung cancer patients whose tumor does not carry an EGFR mutation. The presence of an EGFR mutation predicts a better outcome for lung cancer patients, regardless of treatment received. These mutations are mainly found in patients with a low smoking history (incidence of 50% among U.S. non-smokers with lung cancer) and those of Asian race (incidence of up to 75% in Japanese non-smokers with lung cancer).

Currently, the FDA-approved use of erlotinib or afatinib in the treatment of metastatic non-small cell lung cancer is restricted to the presence of either an EGFR exon 19 deletion or an L858R mutation in the patient’s tumor. The safety and efficacy of these targeted agents have not been established in patients whose lung tumors carry other EGFR mutations, such as those at position G719. Clinical trials are now investigating novel inhibitors that are active across a number of ERBB family members (EGFR, HER2, HER3, HER4) and have reported increased response rates in tumors that carry even these rare EGFR mutations.

PubMed ID's
17189394, 20887192, 17904685, 16204070, 20808254, 18199554, 17349580, 17233841, 16205628, 16043828, 18626007, 17410005, 16314000, 17318210, 17075123, 16204011, 20038723, 19692680, 16014883, 15998907, 18322248, 21252719, 23816967
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Your Matched Clinical Trials

Trial Matches: (D) - Disease, (G) - Gene, (M) - Mutation
Trial Status: Showing Results: 1-10 of 87 Per Page:
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Protocol # Title Location Status Match
NCT03292133 A Study of EGF816 and Gefitinib in TKI-naïve EGFR-mutant Non-Small Cell Lung Cancer A Study of EGF816 and Gefitinib in TKI-naïve EGFR-mutant Non-Small Cell Lung Cancer MGH Open DGM
NCT01553942 Afatinib With CT and RT for EGFR-Mutant NSCLC Afatinib With CT and RT for EGFR-Mutant NSCLC MGH Open DGM
NCT02143466 AZD9291 in Combination With Ascending Doses of Novel Therapeutics AZD9291 in Combination With Ascending Doses of Novel Therapeutics MGH Open DGM
NCT03114319 Dose Finding Study of TNO155 in Adult Patients With Advanced Solid Tumors Dose Finding Study of TNO155 in Adult Patients With Advanced Solid Tumors MGH Open DGM
NCT03256136 Nivolumab in Combination With Chemotherapy, or Nivolumab in Combination With Ipilimumab, in Advanced EGFR-Mutant or ALK-Rearranged NSCLC Nivolumab in Combination With Chemotherapy, or Nivolumab in Combination With Ipilimumab, in Advanced EGFR-Mutant or ALK-Rearranged NSCLC MGH Open DGM
NCT02496663 Osimertinib and Necitumumab in Treating Patients With EGFR-Mutant Stage IV or Recurrent Non-small Cell Lung Cancer Who Have Progressed on a Previous EGFR Tyrosine Kinase Inhibitor Osimertinib and Necitumumab in Treating Patients With EGFR-Mutant Stage IV or Recurrent Non-small Cell Lung Cancer Who Have Progressed on a Previous EGFR Tyrosine Kinase Inhibitor MGH Open DGM
NCT02335944 Study of Safety and Efficacy of EGFR-TKI EGF816 in Combination With cMET Inhibitor INC280 in Non-small Cell Lung Cancer Patients With EGFR Mutation. Study of Safety and Efficacy of EGFR-TKI EGF816 in Combination With cMET Inhibitor INC280 in Non-small Cell Lung Cancer Patients With EGFR Mutation. MGH Open DGM
NCT02387216 A Study of MM-121 in Combination With Chemotherapy Versus Chemotherapy Alone in Heregulin Positive NSCLC A Study of MM-121 in Combination With Chemotherapy Versus Chemotherapy Alone in Heregulin Positive NSCLC MGH Open DG
NCT02716116 A Trial of AP32788 in Non-Small Cell Lung Cancer A Trial of AP32788 in Non-Small Cell Lung Cancer MGH Open DG
NCT02193282 Erlotinib Hydrochloride in Treating Patients With Stage IB-IIIA Non-small Cell Lung Cancer That Has Been Completely Removed by Surgery (An ALCHEMIST Treatment Trial) Erlotinib Hydrochloride in Treating Patients With Stage IB-IIIA Non-small Cell Lung Cancer That Has Been Completely Removed by Surgery (An ALCHEMIST Treatment Trial) MGH Open DG
Trial Status: Showing Results: 1-10 of 87 Per Page:
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Our Lung Cancer Team

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