Melanoma, MAP2K1 (MEK1), Q56P (c.167A>C)

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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. The prognosis for these two types of skin cancer is generally good. Both can often 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 mutated in melanoma. The most common BRAF mutations occur at position V600. Vemurafenib is an effective FDA-approved targeted agent that is available to treat unresectable or metastatic melanoma that has a BRAF V600E mutation. Other melanoma-associated mutations that occur in BRAF also activate the protein abnormally, and can be treated with other targeted agents. Some are sensitive to a combination of BRAF and MEK inhibitors. 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 other genes have been found in melanomas, such as NRAS, MEK, PTEN, TP53, Cyclin D1 (CCND1), CDKN2,and KIT. Mutations in these genes may provide opportunities for enrollment in ongoing clinical trials. Immunology therapies are also being studied in melanoma for patients whose tumors have been tested for specific characteristics. Immuno-therapies are also being tested in combination with targeted therapies in clinical trials at the MGH Cancer Center.

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. The prognosis for these two types of skin cancer is generally good. Both can often 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 mutated in melanoma. The most common BRAF mutations occur at position V600. Vemurafenib is an effective FDA-approved targeted agent that is available to treat unresectable or metastatic melanoma that has a BRAF V600E mutation. Other melanoma-associated mutations that occur in BRAF also activate the protein abnormally, and can be treated with other targeted agents. Some are sensitive to a combination of BRAF and MEK inhibitors. 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 other genes have been found in melanomas, such as NRAS, MEK, PTEN, TP53, Cyclin D1 (CCND1), CDKN2,and KIT. Mutations in these genes may provide opportunities for enrollment in ongoing clinical trials. Immunology therapies are also being studied in melanoma for patients whose tumors have been tested for specific characteristics. Immuno-therapies are also being tested in combination with targeted therapies in clinical trials at the MGH Cancer Center.

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. The prognosis for these two types of skin cancer is generally good. Both can often 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 mutated in melanoma. The most common BRAF mutations occur at position V600. Vemurafenib is an effective FDA-approved targeted agent that is available to treat unresectable or metastatic melanoma that has a BRAF V600E mutation. Other melanoma-associated mutations that occur in BRAF also activate the protein abnormally, and can be treated with other targeted agents. Some are sensitive to a combination of BRAF and MEK inhibitors. 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 other genes have been found in melanomas, such as NRAS, MEK, PTEN, TP53, Cyclin D1 (CCND1), CDKN2,and KIT. Mutations in these genes may provide opportunities for enrollment in ongoing clinical trials. Immunology therapies are also being studied in melanoma for patients whose tumors have been tested for specific characteristics. Immuno-therapies are also being tested in combination with targeted therapies in clinical trials at the MGH Cancer Center.

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. The prognosis for these two types of skin cancer is generally good. Both can often 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 mutated in melanoma. The most common BRAF mutations occur at position V600. Vemurafenib is an effective FDA-approved targeted agent that is available to treat unresectable or metastatic melanoma that has a BRAF V600E mutation. Other melanoma-associated mutations that occur in BRAF also activate the protein abnormally, and can be treated with other targeted agents. Some are sensitive to a combination of BRAF and MEK inhibitors. 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 other genes have been found in melanomas, such as NRAS, MEK, PTEN, TP53, Cyclin D1 (CCND1), CDKN2,and KIT. Mutations in these genes may provide opportunities for enrollment in ongoing clinical trials. Immunology therapies are also being studied in melanoma for patients whose tumors have been tested for specific characteristics. Immuno-therapies are also being tested in combination with targeted therapies in clinical trials at the MGH Cancer Center.

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 Q56P (c.167A>C)  in MAP2K1 (MEK1)
The MEK1 Q56P mutation arises from the nucleotide change c.167A>C in exon 2, resulting in an amino acid substitution of the glutamine (Q) at position 56 by a proline (P).
The MEK1 Q56P mutation arises from the nucleotide change c.167A>C in exon 2, resulting in an amino acid substitution of the glutamine (Q) at position 56 by a proline (P).

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
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Your Matched Clinical Trials

Trial Matches: (D) - Disease, (G) - Gene, (M) - Mutation
Trial Status: Showing Results: 1-10 of 48 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
NCT02967692 A Study of the Anti-PD1 Antibody PDR001, in Combination With Dabrafenib and Trametinib in Advanced Melanoma A Study of the Anti-PD1 Antibody PDR001, in Combination With Dabrafenib and Trametinib in Advanced Melanoma MGH Open DG
NCT03149029 Abbreviated MAPK Targeted Therapy Plus Pembrolizumab in Melanoma Abbreviated MAPK Targeted Therapy Plus Pembrolizumab in Melanoma 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
NCT02561234 A Multiple Dose, Dose Escalation Trial of AEB1102 in Patients With Advanced Solid Tumors A Multiple Dose, Dose Escalation Trial of AEB1102 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
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
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
NCT03148418 A Study in Participants Previously Enrolled in a Genentech− and/or F. Hoffmann-La Roche Ltd-Sponsored Atezolizumab Study (IMbrella A) A Study in Participants Previously Enrolled in a Genentech− and/or F. Hoffmann-La Roche Ltd-Sponsored Atezolizumab Study (IMbrella A) MGH Open D
Trial Status: Showing Results: 1-10 of 48 Per Page:
12345Next »
Our Melanoma Team

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