Lung Cancer, KRAS

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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 KRAS  - General Description
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KRAS is a gene that provides the code for making a protein, KRAS, which is involved primarily in controlling cell division. This protein is part of the MAP kinase signaling cascade (RAS/RAF/MEK/ERK) that relays chemical signals from outside the cell to the cell's nucleus and is primarily involved in controlling cell division. KRAS is an enzyme (a GTPase) that converts a molecule called GTP into GDP. When KRAS is attached (bound) to GDP, it's in its "off" position and can't send signals to the nucleus. But when a GTP molecule arrives and binds to KRAS, KRAS is activated and sends its signal, and then it converts the GTP into GDP and returns to the "off" position.

When mutated, KRAS can act as an oncogene, causing normal cells to become cancerous. The mutations can shift the KRAS protein into the "on" position all the time. KRAS mutations are common in pancreatic, lung and colorectal cancers. These KRAS 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.

Tumor mutation profiling performed clinically at the MGH Cancer Center has identified KRAS mutations across a broad-spectrum of cancer types. The highest incidence of KRAS mutations have been found in pancreatic cancer (70%), colon cancer (30%), lung cancer (25%), cholangiocarcinoma (15-20%), acute myeloid leukemia (15-20%) and endometrial cancer (15-20%). Across the other major tumor types, KRAS mutations have been found in less than 10% of cases that have been tested.

Source: Genetics Home Reference
KRAS (v-Ki-ras2 Kirsten rat sarcoma viral oncogene homolog) is a member of the closely related RAS gene family that includes NRAS and HRAS. These RAS members are small GTPases that transduce extracellular signals to the downstream effectors RAF, PI3K and RALGDS. Ras members are involved in regulating diverse cellular processes including survival, proliferation and differentiation. While activating mutations in the RAS genes lead to sustained GTPase activation and are tumorigenic, each oncogene exerts clear phenotypic differences. KRAS is the most frequently mutated gene from the RAS family, occurring in approximately 20% of all human cancers. Mutational hotspots in KRAS reside primarily in amino acid residues 12, 13 or 61 and function to promote hyperproliferation and suppress differentiation.

Tumor mutation profiling performed clinically at the MGH Cancer Center has identified KRAS mutations across a broad-spectrum of cancer types. The highest incidence of KRAS mutations have been found in pancreatic cancer (70%), colon cancer (30%), lung cancer (25%), cholangiocarcinoma (15-20%), acute myeloid leukemia (15-20%) and endometrial cancer (15-20%). Across the other major tumor types, KRAS mutations have been found in less than 10% of cases that have been tested.

Source: Genetics Home Reference
Expand Collapse KRAS  in Lung Cancer
Genetic alterations in the gene encoding KRAS have been found in lung cancer. The mutations found in KRAS result in a KRAS protein that cannot be regulated normally. The abnormal KRAS protein sends continual growth and proliferation signals to lung cancer cells. Several specific mutations in KRAS may be indications for different treatment recommendations from an oncologist (see list of mutations on the drop-down menu under KRAS).

Testing for all KRAS genetic alterations is available in the MGH Center for Integrated Diagnostics. Treatments for all KRAS-mutant lung cancers are available at the MGH Cancer Center, as are clinical trials testing new and improved treatments for KRAS mutant lung cancer.

Genetic alterations in the gene encoding KRAS have been found in lung cancer. The mutations found in KRAS result in a KRAS protein that cannot be regulated normally. The abnormal KRAS protein sends continual growth and proliferation signals to lung cancer cells. Several specific mutations in KRAS may be indications for different treatment recommendations from an oncologist (see list of mutations on the drop-down menu under KRAS).

Testing for all KRAS genetic alterations is available in the MGH Center for Integrated Diagnostics. Treatments for all KRAS-mutant lung cancers are available at the MGH Cancer Center, as are clinical trials testing new and improved treatments for KRAS mutant lung cancer.

PubMed ID's
21904575, 21125676, 19349489, 21847063, 19671843, 19692680, 21271222, 20921461, 21187500, 21387273, 20022659, 21258250, 21720997, 19667264, 20108024, 21839537, 15696205, 18437168, 21266922, 20609353, 19029981, 23200175
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 85 Per Page:
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Protocol # Title Location Status Match
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
NCT02974725 Study of LXH254 and LTT462 in NSCLC Study of LXH254 and LTT462 in NSCLC MGH Open DG
NCT02079740 Trametinib and Navitoclax in Treating Patients With Advanced or Metastatic Solid Tumors Trametinib and Navitoclax in Treating Patients With Advanced or Metastatic Solid Tumors 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
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
Trial Status: Showing Results: 1-10 of 85 Per Page:
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