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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 protein called the ErbB2 (HER2) growth factor receptor. 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 the cancer cells.

Extra copies of the 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. The presence of amplified HER2 has been reported in approximately 25% of breast tumors, 20% of esophageal tumors, 15% of gastric cancers and 20% of certain ovarian tumors. The FDA has approved the targeted therapies including trastuzumab (Herceptin), pertuzumab (Perjeta), lapatinib (Tykerb), and T-DM1 (Kadcyla) for the treatment of patients with certain kinds of breast cancer in which HER2 is overexpressed. Trastuzumab is also FDA approved to treat gastric cancer with amplification of this receptor.

Mutations in HER2 involving small duplications of the gene can promote resistance to some EGFR targeted therapies, but on the other hand, promote response to certain HER2 inhibitors. While very rare, these mutations are most often associated with non-small cell lung cancer, but have also been described in other malignancies including brain, gastric, breast and ovarian tumors. Tumor mutation profiling performed clinically at the MGH Cancer Center has identified HER2 mutations in a small subset of non-HER2 amplified breast cancer (1%) and non-small cell lung cancers (1%).

Source: Genetics Home Reference
The ERBB2 gene encodes for a cell surface protein that belongs to the ERBB family of receptor tyrosine kinases, known as ErbB2 (more commonly referred to as HER2). Four members of the ERBB family have been identified; EGFR (ERBB1, HER1), ERBB2 (HER2), ERBB3 (HER3) and ERBB4 (HER4). Binding of a ligand induces ERBB receptor homo-/hetero-dimerization and triggers a signaling cascade that drives many cellular responses. These include the activation of PI3K/AKT/mTOR and MAP kinase/ERK pathways, which promote cell survival and proliferation. Although there is no known ligand for HER2, HER2 is the preferred dimerization partner for the other ERBB receptors. In some cancers, HER2 activity is increased through protein overexpression or gene mutation.

The overexpression of HER2 is tightly associated with amplification of the HER2 gene. HER2 amplification has been reported in multiple malignancies, including breast cancer (25% incidence), esophageal cancer (20% incidence), gastric cancer (15% incidence), and mucinous ovarian carcinomas (20% incidence).

Mutations in HER2 have also been identified as an important mechanism that could drive tumor growth and confer resistance to targeted therapies. In-frame duplication/insertions in a region of HER2 exon 20 that is conserved with EGFR have been demonstrated in ~2% of lung cancer patients. Mutations in HER2 receptor have also been described in a small subset of non-HER2 amplified breast cancer (1%).

Source: Genetics Home Reference
PubMed ID's
15864276, 9130710, 15457249, 16397024, 18772890, 16843263, 16988931, 22899400
Expand Collapse ERBB2 (HER2)  in Lung Cancer
Research on the HER2 gene have demonstrated that in a small percentage of lung cancers, there is a common genetic alteration. 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. Clinical trials are underway to treat lung cancer patients found to have this specific mutation with targeted therapies.

Research on the HER2 gene have demonstrated that in a small percentage of lung cancers, there is a common genetic alteration. 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. Clinical trials are underway to treat lung cancer patients found to have this specific mutation with targeted therapies.

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.
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Your Matched Clinical Trials

Trial Matches: (D) - Disease, (G) - Gene
Trial Status: Showing Results: 1-10 of 59 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
NCT02500199 Phase 1, Dose Escalation Study of Pyrotinib in Patients Who Progressed on Prior HER2 Targeted Therapy Phase 1, Dose Escalation Study of Pyrotinib in Patients Who Progressed on Prior HER2 Targeted Therapy MGH Open DG
NCT02335918 A Dose Escalation and Cohort Expansion Study of Anti-CD27 (Varlilumab) and Anti-PD-1 (Nivolumab) in Advanced Refractory Solid Tumors A Dose Escalation and Cohort Expansion Study of Anti-CD27 (Varlilumab) and Anti-PD-1 (Nivolumab) in Advanced Refractory Solid Tumors MGH Open D
NCT02052778 A Dose Finding Study Followed by a Safety and Efficacy Study in Patients With Advanced Solid Tumors or Multiple Myeloma With FGF/FGFR-Related Abnormalities A Dose Finding Study Followed by a Safety and Efficacy Study in Patients With Advanced Solid Tumors or Multiple Myeloma With FGF/FGFR-Related Abnormalities MGH Open D
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
NCT02279433 A First-in-human Study to Evaluate the Safety, Tolerability and Pharmacokinetics of DS-6051b A First-in-human Study to Evaluate the Safety, Tolerability and Pharmacokinetics of DS-6051b 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
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
NCT02327169 A Phase 1B Study of MLN2480 in Combination With MLN0128 or Alisertib, or Paclitaxel, or Cetuximab, or Irinotecan in Adult Patients With Advanced Nonhematologic Malignancies A Phase 1B Study of MLN2480 in Combination With MLN0128 or Alisertib, or Paclitaxel, or Cetuximab, or Irinotecan in Adult Patients With Advanced Nonhematologic Malignancies MGH Open D
NCT02108964 A Phase I/II, Multicenter, Open-label Study of EGFRmut-TKI EGF816, Administered Orally in Adult Patients With EGFRmut Solid Malignancies A Phase I/II, Multicenter, Open-label Study of EGFRmut-TKI EGF816, Administered Orally in Adult Patients With EGFRmut Solid Malignancies MGH Open D
Trial Status: Showing Results: 1-10 of 59 Per Page:
123456Next »
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