Lung Cancer, ERBB2 (HER2)

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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 ERBB2 (HER2)  - General Description
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ERBB2, often called HER2, is a gene that provides the code for making a cell surface growth receptor called the ERBB2 (HER2). When certain growth factors (proteins that stimulate cell growth and division) bind to this receptor, they activate a signaling system inside the cell that ultimately promotes diverse functions such as growth, interaction and adhesion between cells, and ability of the cell to migrate within tissues. In some tumors, the activation of HER2 signaling is an important mechanism that drives the disease process. This can occur through HER2 gene amplification (the most common mechanism) or HER2 gene mutation in cancer cells.

Extra copies of the ERBB2 (HER2) gene (gene amplification) have been found in a number of different cancers. This causes the cancer cells to make excess HER2 (overexpression), which in turn, tells the cells to grow and divide in an uncontrolled manner. Genetic mutations (changes in the DNA sequence that codes the ERBB2 (HER2) protein have also been found in certain tumors.

Source: Genetics Home Reference
ERBB2, often called HER2, is a gene that provides the code for making a cell surface growth receptor called the ERBB2 (HER2). When certain growth factors (proteins that stimulate cell growth and division) bind to this receptor, they activate a signaling system inside the cell that ultimately promotes diverse functions such as growth, interaction and adhesion between cells, and ability of the cell to migrate within tissues. In some tumors, the activation of HER2 signaling is an important mechanism that drives the disease process. This can occur through HER2 gene amplification (the most common mechanism) or HER2 gene mutation in cancer cells.

Extra copies of the ERBB2 (HER2) gene (gene amplification) have been found in a number of different cancers. This causes the cancer cells to make excess HER2 (overexpression), which in turn, tells the cells to grow and divide in an uncontrolled manner. Genetic mutations (changes in the DNA sequence that codes the ERBB2 (HER2) protein have also been found in certain tumors.

Source: Genetics Home Reference
PubMed ID's
15864276, 9130710, 15457249, 16397024, 18772890, 16843263, 16988931, 22899400
Expand Collapse ERBB2 (HER2)  in Lung Cancer
Genetic alterations in the gene that encodes ERBB2 (HER2) have been found in some lung cancers. Several types of genetic alterations have been found in lung cancers, including an "exon 20 insertion". This mutation involves the insertion of extra nucleotides in a specific portion of the HER2 (ERBB2) gene called exon 20. The insertions of these nucleotides are what is called "in-frame", meaning that they are transcribed from the DNA and result in an altered protein. Exon 20 in-frame insertion mutations can affect patient response to certain therapies. Other genetic alterations have been found in ERBB2 (HER2) in some lung cancers. These include gene amplification, where the DNA encoding ERBB2 (HER2) is replicated multiple times, resulting in more transcription and ultimately more of the protein in cells. In other lung tumors, there are mutations in the gene that result in a change in the amino acid sequence of the ERBB2 (HER2) protein. In all three of the above cases, the result is that the cell is unable to regulate ERBB2 (HER2) normally, and the protein sends growth and proliferation signals to the lung tumor cells.

Testing for these ERBB2 (HER2) alterations is available in the Center for Integrated Diagnostics at MGH. Treatments are available for lung cancers harboring these genetic alterations. In addition, clinical trials are available to test improved treatments at the MGH Cancer Center.

Genetic alterations in the gene that encodes ERBB2 (HER2) have been found in some lung cancers. Several types of genetic alterations have been found in lung cancers, including an "exon 20 insertion". This mutation involves the insertion of extra nucleotides in a specific portion of the HER2 (ERBB2) gene called exon 20. The insertions of these nucleotides are what is called "in-frame", meaning that they are transcribed from the DNA and result in an altered protein. Exon 20 in-frame insertion mutations can affect patient response to certain therapies. Other genetic alterations have been found in ERBB2 (HER2) in some lung cancers. These include gene amplification, where the DNA encoding ERBB2 (HER2) is replicated multiple times, resulting in more transcription and ultimately more of the protein in cells. In other lung tumors, there are mutations in the gene that result in a change in the amino acid sequence of the ERBB2 (HER2) protein. In all three of the above cases, the result is that the cell is unable to regulate ERBB2 (HER2) normally, and the protein sends growth and proliferation signals to the lung tumor cells.

Testing for these ERBB2 (HER2) alterations is available in the Center for Integrated Diagnostics at MGH. Treatments are available for lung cancers harboring these genetic alterations. In addition, clinical trials are available to test improved treatments at the MGH Cancer Center.

PubMed ID's
15457249, 16397024, 15753357, 16140923, 16988931, 16863509, 17001163, 16825508, 17538169, 18948947, 20018398, 14679114, 21353324, 15753357, 22071781, 21353324, 16843263, 22325357, 16775247
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.
Our Lung Cancer Team

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Your Matched Clinical Trials

Trial Matches: (D) - Disease, (G) - Gene
Trial Status: Showing Results: 1-10 of 85 Per Page:
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Protocol # Title Location Status Match
NCT02716116 A Trial of AP32788 in Non-Small Cell Lung Cancer A Trial of AP32788 in Non-Small Cell Lung Cancer MGH Open DG
NCT03318939 Phase 2 Study of Poziotinib in Patients With NSCLC With EGFR or HER2 Exon 20 Insertion Mutation Phase 2 Study of Poziotinib in Patients With NSCLC With EGFR or HER2 Exon 20 Insertion Mutation 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
NCT02952729 Study of Antibody Drug Conjugate in Patients With Advanced Breast Cancer Expressing HER2 Study of Antibody Drug Conjugate in Patients With Advanced Breast Cancer Expressing HER2 MGH Open DG
NCT02637531 A Dose-Escalation Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of IPI-549 A Dose-Escalation Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of IPI-549 MGH Open D
NCT03192345 A First-in-human Study of the Safety, Pharmacokinetics, Pharmacodynamics and Anti-tumor Activity of SAR439459 Monotherapy and Combination of SAR439459 and REGN2810 in Patients With Advanced Solid Tumors A First-in-human Study of the Safety, Pharmacokinetics, Pharmacodynamics and Anti-tumor Activity of SAR439459 Monotherapy and Combination of SAR439459 and REGN2810 in Patients With Advanced Solid Tumors MGH Open D
NCT02897765 A Personal Cancer Vaccine (NEO-PV-01) w/ Nivolumab for Patients With Melanoma, Lung Cancer or Bladder Cancer A Personal Cancer Vaccine (NEO-PV-01) w/ Nivolumab for Patients With Melanoma, Lung Cancer or Bladder Cancer MGH Open D
NCT03380871 A Personal Cancer Vaccine (NEO-PV-01) With Pembrolizumab and Chemotherapy for Patients With Lung Cancer A Personal Cancer Vaccine (NEO-PV-01) With Pembrolizumab and Chemotherapy for Patients With Lung Cancer MGH Open D
NCT02715284 A Phase 1 Dose Escalation and Cohort Expansion Study of TSR-042, an Anti-PD-1 Monoclonal Antibody, in Patients With Advanced Solid Tumors A Phase 1 Dose Escalation and Cohort Expansion Study of TSR-042, an Anti-PD-1 Monoclonal Antibody, in Patients With Advanced Solid Tumors MGH Open D
NCT03134638 A Phase 1 Study of SY-1365 in Adult Patients With Advanced Solid Tumors A Phase 1 Study of SY-1365 in Adult Patients With Advanced Solid Tumors MGH Open D
Trial Status: Showing Results: 1-10 of 85 Per Page:
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