Lung Cancer, RET

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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 RET  - General Description
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RET is a gene that provides the code for making a protein that is involved in signaling within cells, acting as the receptor for chemical signals that help the cell respond to its surroundings. The RET protein is a receptor tyrosine kinase (RTK) that is found on the cell surface. When certain molecules known as growth factors attach (bind to) the external portion of the receptor, a complex chain of chemical reactions is triggered inside the cell. The chain reaction relays the signal that was received by the receptor, telling the cell to undergo certain changes, such as dividing or maturing to take on specialized functions. This protein seems to be essential for normal development of several kinds of nerve cells, including nerves in the intestine and the autonomic nervous system, which controls heart rate and other functions that occur without being thought about. The RET protein is also needed for normal kidney development and the production of sperm.

Chromosomal rearrangements involving the RET gene are one of the most common causes of a nonhereditary form of thyroid cancer called papillary thyroid carcinoma (RET/PTC). Another type of thyroid cancer, medullary thyroid carcinoma, also can be caused by mutations in the RET gene. These mutations are said to be somatic because, instead of coming from a parent and being present in every cell (hereditary), they are acquired during the course of a person's life and are found only in cells that become cancerous.

Source: Genetics Home Reference
RET is a gene that provides the code for making a protein that is involved in signaling within cells, acting as the receptor for chemical signals that help the cell respond to its surroundings. The RET protein is a receptor tyrosine kinase (RTK) that is found on the cell surface. When certain molecules known as growth factors attach (bind to) the external portion of the receptor, a complex chain of chemical reactions is triggered inside the cell. The chain reaction relays the signal that was received by the receptor, telling the cell to undergo certain changes, such as dividing or maturing to take on specialized functions. This protein seems to be essential for normal development of several kinds of nerve cells, including nerves in the intestine and the autonomic nervous system, which controls heart rate and other functions that occur without being thought about. The RET protein is also needed for normal kidney development and the production of sperm.

Chromosomal rearrangements involving the RET gene are one of the most common causes of a nonhereditary form of thyroid cancer called papillary thyroid carcinoma (RET/PTC). Another type of thyroid cancer, medullary thyroid carcinoma, also can be caused by mutations in the RET gene. These mutations are said to be somatic because, instead of coming from a parent and being present in every cell (hereditary), they are acquired during the course of a person's life and are found only in cells that become cancerous.

Source: Genetics Home Reference
Expand Collapse RET  in Lung Cancer
Genetic alterations in the gene encoding the RET protein have been found in lung cancers. The type of genetic alteration found in RET is called a gene translocation. In this alteration, a portion of the RET gene breaks away from the rest of the gene, and inserts itself into a different gene in another location of the DNA. The resulting protein is part RET, and part of the protein that the RET gene inserted itself into. Cells are unable to regulate this "fusion" protein that results from such a translocation. In lung cancer, the product of RET translocations are fusion proteins that are constantly activated, providing tumor cells signals that stimulate growth and proliferation.

Testing for genetic translocations in RET is performed in the MGH Center for Integrated Diagnostics. Treatment for RET-mutated lung cancers is available at the MGH Cancer Center, as are clinical trials testing new therapies and combination therapies for patients.

Genetic alterations in the gene encoding the RET protein have been found in lung cancers. The type of genetic alteration found in RET is called a gene translocation. In this alteration, a portion of the RET gene breaks away from the rest of the gene, and inserts itself into a different gene in another location of the DNA. The resulting protein is part RET, and part of the protein that the RET gene inserted itself into. Cells are unable to regulate this "fusion" protein that results from such a translocation. In lung cancer, the product of RET translocations are fusion proteins that are constantly activated, providing tumor cells signals that stimulate growth and proliferation.

Testing for genetic translocations in RET is performed in the MGH Center for Integrated Diagnostics. Treatment for RET-mutated lung cancers is available at the MGH Cancer Center, as are clinical trials testing new therapies and combination therapies for patients.

PubMed ID's
22327622, 22327623, 22327624, 23150706, 23378251, 23533264
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 84 Per Page:
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Protocol # Title Location Status Match
NCT03157128 Phase 1 Study of LOXO-292 in Patients With Advanced Solid Tumors, RET-Fusion Lung Cancer and Medullary Thyroid Cancer Phase 1 Study of LOXO-292 in Patients With Advanced Solid Tumors, RET-Fusion Lung Cancer and Medullary Thyroid Cancer MGH Open DG
NCT03037385 Phase 1 Study of the Highly-selective RET Inhibitor BLU-667 in Patients With Thyroid Cancer, Non-Small Cell Lung Cancer, and Other Advanced Solid Tumors Phase 1 Study of the Highly-selective RET Inhibitor BLU-667 in Patients With Thyroid Cancer, Non-Small Cell Lung Cancer, and Other Advanced Solid Tumors MGH Open DG
NCT02219711 Phase 1/1b Study of MGCD516 in Patients With Advanced Cancer Phase 1/1b Study of MGCD516 in Patients With Advanced Cancer 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
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
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
Trial Status: Showing Results: 1-10 of 84 Per Page:
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