Lung Cancer, Beta-Catenin (CTNNB1), all mutations

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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 Beta-Catenin (CTNNB1)  - General Description
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The CTNNB1 gene encodes a protein called beta-catenin that has several important functions in the cell. These include being involved in cell to cell contacts at adherens junctions, and being involved in the WNT signaling pathway.

The first role beta-catenin is integral to is in participating in cell to cell contacts. Where cells are in contact with one another, beta catenin is part of a complex of proteins that form what are called adherens junctions. Adherens junctions are protein complexes that occur at cell-to-cell junctions and are essential for the formation and maintenance of epithelial cell layers. In this role, beta-catenin functions to anchor the actin cytoskeleton of cells, and to transmit the contact inhibition signal that causes cells to stop dividing once the epithelial layer of cells is complete. Beta catenin also has a role in cell migration.

In a second role, beta-catenin is involved in the Wnt signaling pathway (see graphic above). In the absence of a Wnt signal, beta catenin is normally kept at very low levels within the cell by a destruction complex. This destruction complex includes proteins called GSK-3, APC, and axin, and is responsible for degrading beta catenin. When a Wnt ligand binds to a Wnt receptor on the cell surface, this triggers a signal in the cell that causes the dissociation of the destruction complex, and beta catenin is no longer degraded. Instead, it builds up in the cytoplasm of the cell, and binds to T cell factor (TCF). Beta catenin/TCF translocate into the nucleus, and bind to Wnt target genes that promote growth, including C-Myc and Cyclin D1.

Mutations in the CTNNB1 gene that encodes the beta catenin protein result in the abnormal accumulation of the beta catenin protein in the cell. These and are frequently found in some cancers including colorectal cancer, endometrial and uterine cancers, as well as medulloblastomas. Mutations in CTNNB1/the beta catenin protein also occur in adenocarcinoma of the lung and colorectal cancers, and less frequently in liver cancer, gastric adenocarcinoma, bladder cancer, desmoid tumors, and pilomatrixoma.

Source: TumorPortal.org
The CTNNB1 gene encodes a protein called beta-catenin that has several important functions in the cell. These include being involved in cell to cell contacts at adherens junctions, and being involved in the WNT signaling pathway.

The first role beta-catenin is integral to is in participating in cell to cell contacts. Where cells are in contact with one another, beta catenin is part of a complex of proteins that form what are called adherens junctions. Adherens junctions are protein complexes that occur at cell-to-cell junctions and are essential for the formation and maintenance of epithelial cell layers. In this role, beta-catenin functions to anchor the actin cytoskeleton of cells, and to transmit the contact inhibition signal that causes cells to stop dividing once the epithelial layer of cells is complete. Beta catenin also has a role in cell migration.

In a second role, beta-catenin is involved in the Wnt signaling pathway (see graphic above). In the absence of a Wnt signal, beta catenin is normally kept at very low levels within the cell by a destruction complex. This destruction complex includes proteins called GSK-3, APC, and axin, and is responsible for degrading beta catenin. When a Wnt ligand binds to a Wnt receptor on the cell surface, this triggers a signal in the cell that causes the dissociation of the destruction complex, and beta catenin is no longer degraded. Instead, it builds up in the cytoplasm of the cell, and binds to T cell factor (TCF). Beta catenin/TCF translocate into the nucleus, and bind to Wnt target genes that promote growth, including C-Myc and Cyclin D1.

Mutations in the CTNNB1 gene that encodes the beta catenin protein result in the abnormal accumulation of the beta catenin protein in the cell. These and are frequently found in some cancers including colorectal cancer, endometrial and uterine cancers, as well as medulloblastomas. Mutations in CTNNB1/the beta catenin protein also occur in adenocarcinoma of the lung and colorectal cancers, and less frequently in liver cancer, gastric adenocarcinoma, bladder cancer, desmoid tumors, and pilomatrixoma.

Source: TumorPortal.org
PubMed ID's
19619488, 22682243
Expand Collapse all mutations  in Beta-Catenin (CTNNB1)
Genetic alterations in CTNNB1, the gene that encodes the beta-catenin protein, have been found in many cancers with varying frequencies. CTNNB1 protein is an important participant in the WNT signal pathway (see above). The mutations found in CTNNB1 result in an accumulation of beta catenin in cells, which stimulates growth even in the absence of a WNT signal, contributing to the development of cancer.

Genetic alterations in CTNNB1, the gene that encodes the beta-catenin protein, have been found in many cancers with varying frequencies. CTNNB1 protein is an important participant in the WNT signal pathway (see above). The mutations found in CTNNB1 result in an accumulation of beta catenin in cells, which stimulates growth even in the absence of a WNT signal, contributing to the development of cancer.


CTNNB1 mutations have been found in lung cancers, and cause the beta-catenin protein to behave in an unregulated manner. This lack of normal regulation leads to an accumulation of beta-catenin in the cell, promoting growth and cell proliferation.

CTNNB1 mutations have been found in lung cancers, and cause the beta-catenin protein to behave in an unregulated manner. This lack of normal regulation leads to an accumulation of beta-catenin in the cell, promoting growth and cell proliferation.

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Your Matched Clinical Trials

Trial Matches: (D) - Disease, (G) - Gene, (M) - Mutation
Trial Status: Showing Results: 1-10 of 85 Per Page:
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Protocol # Title Location Status Match
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
NCT02817633 A Phase 1 Study of TSR-022, an Anti-TIM-3 Monoclonal Antibody, in Patients With Advanced Solid Tumors A Phase 1 Study of TSR-022, an Anti-TIM-3 Monoclonal Antibody, in Patients With Advanced Solid Tumors MGH Open D
NCT03202940 A Phase IB/II Study of Alectinib Combined With Cobimetinib in Advanced ALK-Rearranged (ALK+) NSCLC A Phase IB/II Study of Alectinib Combined With Cobimetinib in Advanced ALK-Rearranged (ALK+) NSCLC MGH Open D
NCT03139370 A Study Evaluating the Safety and Efficacy of MAGE-A3/A6 T Cell Receptor Engineered T Cells (KITE-718) in HLA-DPB1*04:01 Positive Subjects With Advanced Cancers A Study Evaluating the Safety and Efficacy of MAGE-A3/A6 T Cell Receptor Engineered T Cells (KITE-718) in HLA-DPB1*04:01 Positive Subjects With Advanced Cancers MGH Open D
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
Trial Status: Showing Results: 1-10 of 85 Per Page:
123456789Next »
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