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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 BRAF  - General Description
CLICK IMAGE FOR MORE INFORMATION
The BRAF gene encodes a serine/threonine kinase that activates the growth-promoting MAP kinase signaling cascade. BRAF is commonly activated by somatic point mutations in human cancers, most frequently by mutations located within the kinase domain at amino acid positions G466, G469, L597 and V600.

In regards to treatment, the Food and Drug Administration (FDA) approved the BRAF inhibitor, vemurafenib, for the treatment of unresectable or metastatic melanoma patients harboring specifically the BRAF V600E mutation, as detected by an FDA-approved test. In addition, there are a growing number of targeted agents that are being evaluated for the treatment of various BRAF-mutant advanced cancers, including other RAF kinase inhibitors and/or MEK inhibitors. Recently, the combination of the BRAF inhibitor dabrafenib with the MEK inhibitor trametinib was approved by FDA for the treatment of patients with BRAF V600E or V600K mutations.

Tumor mutation profiling performed clinically at the MGH Cancer Center has identified the highest incidence of BRAF mutations in thyroid cancer (30-40%), melanoma (20-30%) and colon cancer (10-15%).

To read more about the various BRAF based trials ongoing at the MGH Cancer Center, click on the "disease-gene-mutation" tab on the web page, and select relevant information. Current trials will appear as a ist under the posted information.


Source: Genetics Home Reference
The BRAF gene encodes a serine/threonine kinase that activates the growth-promoting MAP kinase signaling cascade. BRAF is commonly activated by somatic point mutations in human cancers, most frequently by mutations located within the kinase domain at amino acid positions G466, G469, L597 and V600.

In regards to treatment, the Food and Drug Administration (FDA) approved the BRAF inhibitor, vemurafenib, for the treatment of unresectable or metastatic melanoma patients harboring specifically the BRAF V600E mutation, as detected by an FDA-approved test. In addition, there are a growing number of targeted agents that are being evaluated for the treatment of various BRAF-mutant advanced cancers, including other RAF kinase inhibitors and/or MEK inhibitors. Recently, the combination of the BRAF inhibitor dabrafenib with the MEK inhibitor trametinib was approved by FDA for the treatment of patients with BRAF V600E or V600K mutations.

Tumor mutation profiling performed clinically at the MGH Cancer Center has identified the highest incidence of BRAF mutations in thyroid cancer (30-40%), melanoma (20-30%) and colon cancer (10-15%).

To read more about the various BRAF based trials ongoing at the MGH Cancer Center, click on the "disease-gene-mutation" tab on the web page, and select relevant information. Current trials will appear as a ist under the posted information.

Source: Genetics Home Reference
PubMed ID's
12068308, 15947100, 20401974, 20425073, 21606968
Expand Collapse G469E (c.1406G>A)  in BRAF
The BRAF G469E mutation arises from a single nucleotide change (c.1406G>A) and results in an amino acid substitution of the glycine (G) at position 469 by a glutamic acid (E).
The BRAF G469E mutation arises from a single nucleotide change (c.1406G>A) and results in an amino acid substitution of the glycine (G) at position 469 by a glutamic acid (E).

BRAF mutations are found in 1-3% of lung cancers. They are more frequent in adenocarcinoma tumor subtypes as compared to squamous cell carcinomas of the lung. It should also be noted that BRAF mutations are usually found in tumors that do not have EGFR or ALK driver mutations.

It has not been determined whether BRAF-mutant lung cancers similarly benefit from treatment with the BRAF inhibitor vemurafenib, as has been demonstrated in malignant melanoma. Importantly, vemurafenib has higher activity in BRAF V600E mutant tumors, and the incidence of BRAF mutations other than V600E is significantly higher in lung cancer than in other tumors. An initial study of NSCLC patients treated with dabrafenib, a BRAF inhibitor with activity against tumors with BRAF V600E mutation, has demonstrated many responses among the 20 patients treated (“Interim results of phase II study of BRF113928 of dabrafenib in BRAF V600E mutation-positive NSCLC patients” David Planchard, et al., 2013 ASCO Meeting). Preclinical and clinical studies suggest that downstream inhibition of MEK may be an alternative treatment course in BRAF mutation-positive lung cancer. Multiple clinical trials with BRAF and/or MEK inhibitors are currently underway.

BRAF mutations are found in 1-3% of lung cancers. They are more frequent in adenocarcinoma tumor subtypes as compared to squamous cell carcinomas of the lung. It should also be noted that BRAF mutations are usually found in tumors that do not have EGFR or ALK driver mutations.

It has not been determined whether BRAF-mutant lung cancers similarly benefit from treatment with the BRAF inhibitor vemurafenib, as has been demonstrated in malignant melanoma. Importantly, vemurafenib has higher activity in BRAF V600E mutant tumors, and the incidence of BRAF mutations other than V600E is significantly higher in lung cancer than in other tumors. An initial study of NSCLC patients treated with dabrafenib, a BRAF inhibitor with activity against tumors with BRAF V600E mutation, has demonstrated many responses among the 20 patients treated (“Interim results of phase II study of BRF113928 of dabrafenib in BRAF V600E mutation-positive NSCLC patients” David Planchard, et al., 2013 ASCO Meeting). Preclinical and clinical studies suggest that downstream inhibition of MEK may be an alternative treatment course in BRAF mutation-positive lung cancer. Multiple clinical trials with BRAF and/or MEK inhibitors are currently underway.

PubMed ID's
17699718, 21483012, 19010912, 20802351, 21483012, 19010912, 20802351
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Your Matched Clinical Trials

Trial Matches: (D) - Disease, (G) - Gene, (M) - Mutation
Trial Status: Showing Results: 1-10 of 51 Per Page:
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Protocol # Title Location Status Match
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 DGM
NCT02857270 A Study of LY3214996 Administered Alone or in Combination With Other Agents in Participants With Advanced/Metastatic Cancer A Study of LY3214996 Administered Alone or in Combination With Other Agents in Participants With Advanced/Metastatic Cancer MGH Open DG
NCT02437136 Ph1b/2 Dose-Escalation Study of Entinostat With Pembrolizumab in NSCLC With Expansion Cohorts in NSCLC and Melanoma Ph1b/2 Dose-Escalation Study of Entinostat With Pembrolizumab in NSCLC With Expansion Cohorts in NSCLC and Melanoma 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
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 51 Per Page:
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