Melanoma, MAP2K1 (MEK1)

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Expand Collapse Melanoma  - General Description Skin cancer is a malignant tumor that grows in the skin cells and accounts for more than 50 percent of all cancers. There are generally three different types of skin cancer: basal cell carcinoma, squamous cell carcinoma and melanoma.

Basal cell carcinoma and squamous cell carcinoma usually appear on sun-exposed areas of the body. Prognosis is generally good and both of these cancer types can usually be effectively treated through surgery, with a minority of cases requiring radiation treatment.

Melanoma is the most aggressive form of skin cancer and arises in the cells that produce pigment (color) in the skin. BRAF is the gene that is most frequently activated by mutation in this malignancy and the common BRAF V600E and V600K mutations have been associated with a more aggressive clinical course and shorter survival. Vemurafenib is a new and effective FDA-approved targeted agent that is available to treat unresectable or metastatic melanoma based on the presence of a BRAF V600E mutation. Preclinical data has indicated that the rare BRAF V600R mutation may also be sensitive to vemurafenib. Also, the BRAF L597R mutation has been found to confer sensitivity to downstream MEK inhibitors. Most 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. While less frequent, mutations in cancer genes such as NRAS, MEK, PTEN, PIK3CA and KIT may provide opportunities for enrollment into ongoing clinical trials.

Skin cancer is a malignant tumor that grows in the skin cells and accounts for more than 50 percent of all cancers. There are generally three different types of skin cancer: basal cell carcinoma, squamous cell carcinoma and melanoma.

Basal cell carcinoma and squamous cell carcinoma usually appear on sun-exposed areas of the body. Prognosis is generally good and both of these cancer types can usually be effectively treated through surgery, with a minority of cases requiring radiation treatment.

Melanoma is the most aggressive form of skin cancer and arises in the cells that produce pigment (color) in the skin. BRAF is the gene that is most frequently activated by mutation in this malignancy and the common BRAF V600E and V600K mutations have been associated with a more aggressive clinical course and shorter survival. Vemurafenib is a new and effective FDA-approved targeted agent that is available to treat unresectable or metastatic melanoma based on the presence of a BRAF V600E mutation. Preclinical data has indicated that the rare BRAF V600R mutation may also be sensitive to vemurafenib. Also, the BRAF L597R mutation has been found to confer sensitivity to downstream MEK inhibitors. Most 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. While less frequent, mutations in cancer genes such as NRAS, MEK, PTEN, PIK3CA and KIT may provide opportunities for enrollment into ongoing clinical trials.

Skin cancer is a malignant tumor that grows in the skin cells and accounts for more than 50 percent of all cancers. There are generally three different types of skin cancer: basal cell carcinoma, squamous cell carcinoma and melanoma.

Basal cell carcinoma and squamous cell carcinoma usually appear on sun-exposed areas of the body. Prognosis is generally good and both of these cancer types can usually be effectively treated through surgery, with a minority of cases requiring radiation treatment.

Melanoma is the most aggressive form of skin cancer and arises in the cells that produce pigment (color) in the skin. BRAF is the gene that is most frequently activated by mutation in this malignancy and the common BRAF V600E and V600K mutations have been associated with a more aggressive clinical course and shorter survival. Vemurafenib is a new and effective FDA-approved targeted agent that is available to treat unresectable or metastatic melanoma based on the presence of a BRAF V600E mutation. Preclinical data has indicated that the rare BRAF V600R mutation may also be sensitive to vemurafenib. Also, the BRAF L597R mutation has been found to confer sensitivity to downstream MEK inhibitors. Most 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. While less frequent, mutations in cancer genes such as NRAS, MEK, PTEN, PIK3CA and KIT may provide opportunities for enrollment into ongoing clinical trials.

Skin cancer is a malignant tumor that grows in the skin cells and accounts for more than 50 percent of all cancers. There are generally three different types of skin cancer: basal cell carcinoma, squamous cell carcinoma and melanoma.

Basal cell carcinoma and squamous cell carcinoma usually appear on sun-exposed areas of the body. Prognosis is generally good and both of these cancer types can usually be effectively treated through surgery, with a minority of cases requiring radiation treatment.

Melanoma is the most aggressive form of skin cancer and arises in the cells that produce pigment (color) in the skin. BRAF is the gene that is most frequently activated by mutation in this malignancy and the common BRAF V600E and V600K mutations have been associated with a more aggressive clinical course and shorter survival. Vemurafenib is a new and effective FDA-approved targeted agent that is available to treat unresectable or metastatic melanoma based on the presence of a BRAF V600E mutation. Preclinical data has indicated that the rare BRAF V600R mutation may also be sensitive to vemurafenib. Also, the BRAF L597R mutation has been found to confer sensitivity to downstream MEK inhibitors. Most 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. While less frequent, mutations in cancer genes such as NRAS, MEK, PTEN, PIK3CA and KIT may provide opportunities for enrollment into ongoing clinical trials.

PubMed ID's
21343559, 22798288, 20551065
Expand Collapse MAP2K1 (MEK1)  - General Description
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The MAP2K1 gene encodes for a protein known as MEK1 protein kinase. This protein is part of a signaling pathway known as the MAP kinase cascade that relays chemical signals from outside the cell to the cell's nucleus and helps control various cellular processes, including cell proliferation, cell differentiation and cell death. MAP2K1 is very similar to the gene MAP2K2 (endoding the protein MEK2 protein kinase), which is also part of the same pathway. Both the MEK1 and the MEK2 protein kinases seem to be essential for normal development and survival before and after birth.

Mutations in MAP2K1 have been identified in lung cancer, colon cancer and melanoma of the skin. Since MEK1 is a link in the middle of the MAP kinase cascade, drugs that block its action may be effective in treating cancers caused by defective genes that affect links in the first part of this pathway, such as activating mutations in BRAF, KRAS and NRAS.

Source: Genetics Home Reference
The MAP2K1 (MEK1) gene encodes for a serine/threonine kinase component of the MAP kinase cascade, which regulates multiple cellular processes including proliferation, survival and differentiation. Mutations in MEK1 have been described at low prevalence in lung cancer, colon cancer, melanoma and ovarian cancer cell lines.

Source: Genetics Home Reference
PubMed ID's
18632602, 19411838, 18060073
Expand Collapse MAP2K1 (MEK1)  in Melanoma
Preclinical studies have suggested that MEK1 mutations confer resistance to BRAF and MEK inhibitors. More specifically, the gain of a mutation in MEK1 (such as the mutations P124L and C121S) has been observed in the metastatic lesions that develop during the onset of treatment failure. In metastatic lesions taken from two melanoma patients, acquired MEK1 mutations were found in a patient during treatment with the MEK inhibitor selumetinib and the second one upon resistance to BRAF inhibitor vemurafenib after an initial dramatic response. In the same reports, a MEK1-mutant cell line derived from one of the patients and BRAF V600E-mutant melanoma cell lines expressing experimental MEK1 mutations were found to be resistant to BRAF and MEK inhibition.

Preclinical studies have suggested that MEK1 mutations confer resistance to BRAF and MEK inhibitors. More specifically, the gain of a mutation in MEK1 (such as the mutations P124L and C121S) has been observed in the metastatic lesions that develop during the onset of treatment failure. In metastatic lesions taken from two melanoma patients, acquired MEK1 mutations were found in a patient during treatment with the MEK inhibitor selumetinib and the second one upon resistance to BRAF inhibitor vemurafenib after an initial dramatic response. In the same reports, a MEK1-mutant cell line derived from one of the patients and BRAF V600E-mutant melanoma cell lines expressing experimental MEK1 mutations were found to be resistant to BRAF and MEK inhibition.

PubMed ID's
19915144, 21383288
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 23 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
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
NCT02110355 A Phase 1b/2a Study Evaluating AMG 232 in Metastatic Melanoma A Phase 1b/2a Study Evaluating AMG 232 in Metastatic Melanoma MGH Open D
NCT01714739 A Study of an Anti-KIR Antibody in Combination With an Anti-PD1 Antibody in Patients With Advanced Solid Tumors A Study of an Anti-KIR Antibody in Combination With an Anti-PD1 Antibody in Patients With Advanced Solid Tumors MGH Open D
NCT01325441 A Study of BBI608 Administered With Paclitaxel in Adult Patients With Advanced Malignancies A Study of BBI608 Administered With Paclitaxel in Adult Patients With Advanced Malignancies MGH Open D
NCT02228811 A Study of DCC-2701 in Participants With Advanced Solid Tumors A Study of DCC-2701 in Participants With Advanced Solid Tumors MGH Open D
NCT02471846 A Study of GDC-0919 and Atezolizumab Combination Treatment in Participants With Locally Advanced or Metastatic Solid Tumors A Study of GDC-0919 and Atezolizumab Combination Treatment in Participants With Locally Advanced or Metastatic Solid Tumors MGH Open D
NCT02082210 A Study of LY2875358 in Combination With Ramucirumab (LY3009806) in Participants With Advanced Cancer A Study of LY2875358 in Combination With Ramucirumab (LY3009806) in Participants With Advanced Cancer MGH Open D
NCT02320058 A Study to Evaluate Safety and Effectiveness in Patients With Melanoma That Has Spread to the Brain Treated With Nivolumab in Combination With Ipilimumab Followed by Nivolumab by Itself A Study to Evaluate Safety and Effectiveness in Patients With Melanoma That Has Spread to the Brain Treated With Nivolumab in Combination With Ipilimumab Followed by Nivolumab by Itself MGH Open D
NCT02642016 A Study to Evaluate the Safety and Pharmacokinetics of KTN0158 in Adult Patients With Advanced Solid Tumors A Study to Evaluate the Safety and Pharmacokinetics of KTN0158 in Adult Patients With Advanced Solid Tumors MGH Open D
Trial Status: Showing Results: 1-10 of 23 Per Page:
123Next »
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