Melanoma, BRAF

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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 BRAF  - General Description
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The BRAF gene encodes for 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 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%).

Source: Genetics Home Reference
The BRAF gene encodes for 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 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%).

Source: Genetics Home Reference
PubMed ID's
12068308, 15947100, 20401974, 20425073, 21606968
Expand Collapse BRAF  in Melanoma
Mutated BRAF is a validated therapeutic target in the treatment of advanced (metastatic) or unresectable (cannot be removed by surgery) melanoma, with several therapies already receiving FDA approval for clinical use. The BRAF inhibitors vemurafenib as well as dabrafenib have each individually received FDA-approval for the treatment of unresectable or metastatic melanoma patients whose tumor carry the BRAF V600E mutation, as detected by an FDA-approved test. The MEK inhibitor trametinib has also been approved by the FDA for the treatment of patients with metastatic or unresectable melanoma carrying the BRAF V600E or V600K gene mutations. However, patients who previously used BRAF inhibitors do not appear to benefit from trametinib.

Preclinical studies have suggested that other BRAF mutations, such as BRAF V600R, may also be sensitive to BRAF inhibitors. However, these other mutations do not currently direct the FDA-approved use of these drugs. Furthermore, the combination of the BRAF inhibitor dabrafenib with the MEK inhibitor trametinib may additionally improve progression-free survival in the treatment of advanced melanoma, which is currently being investigated in a phase III clinical trial.

There are a growing number of other targeted agents that are being evaluated for the treatment of BRAF-mutant advanced melanoma, including other RAF kinase inhibitors, MEK inhibitors and/or ERK inhibitors.

The BRAF V600E and V600K mutations specifically have been associated with a more aggressive clinical course and shorter survival for patients with metastatic melanoma that have NOT been treated with a BRAF inhibitor. The prognostic significance of other BRAF mutations has not been determined.

Mutated BRAF is a validated therapeutic target in the treatment of advanced (metastatic) or unresectable (cannot be removed by surgery) melanoma, with several therapies already receiving FDA approval for clinical use. The BRAF inhibitors vemurafenib as well as dabrafenib have each individually received FDA-approval for the treatment of unresectable or metastatic melanoma patients whose tumor carry the BRAF V600E mutation, as detected by an FDA-approved test. The MEK inhibitor trametinib has also been approved by the FDA for the treatment of patients with metastatic or unresectable melanoma carrying the BRAF V600E or V600K gene mutations. However, patients who previously used BRAF inhibitors do not appear to benefit from trametinib.

Preclinical studies have suggested that other BRAF mutations, such as BRAF V600R, may also be sensitive to BRAF inhibitors. However, these other mutations do not currently direct the FDA-approved use of these drugs. Furthermore, the combination of the BRAF inhibitor dabrafenib with the MEK inhibitor trametinib may additionally improve progression-free survival in the treatment of advanced melanoma, which is currently being investigated in a phase III clinical trial.

There are a growing number of other targeted agents that are being evaluated for the treatment of BRAF-mutant advanced melanoma, including other RAF kinase inhibitors, MEK inhibitors and/or ERK inhibitors.

The BRAF V600E and V600K mutations specifically have been associated with a more aggressive clinical course and shorter survival for patients with metastatic melanoma that have NOT been treated with a BRAF inhibitor. The prognostic significance of other BRAF mutations has not been determined.

PubMed ID's
21343559, 21606968, 20551065, 22798288, 22735384, 20425073, 22663011, 23020132
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 Melanoma Team

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Your Matched Clinical Trials

Trial Matches: (D) - Disease, (G) - Gene
Trial Status: Showing Results: 1-10 of 22 Per Page:
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Protocol # Title Location Status Match
NCT01656642 A Phase 1b Study of Atezolizumab in Combination With Vemurafenib or Vemurafenib Plus Cobimetinib in Participants With BRAFV600-Mutation Positive Metastatic Melanoma A Phase 1b Study of Atezolizumab in Combination With Vemurafenib or Vemurafenib Plus Cobimetinib in Participants With BRAFV600-Mutation Positive Metastatic Melanoma MGH Open DG
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 DG
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 DG
NCT02752074 A Phase 3 Study of Pembrolizumab + Epacadostat or Placebo in Subjects With Unresectable or Metastatic Melanoma A Phase 3 Study of Pembrolizumab + Epacadostat or Placebo in Subjects With Unresectable or Metastatic Melanoma MGH Open DG
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 DG
NCT01989585 Dabrafenib, Trametinib, and Navitoclax in Treating Patients With BRAF Mutant Melanoma or Solid Tumors That Are Metastatic or Cannot Be Removed by Surgery Dabrafenib, Trametinib, and Navitoclax in Treating Patients With BRAF Mutant Melanoma or Solid Tumors That Are Metastatic or Cannot Be Removed by Surgery 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
NCT02296112 Trametinib in Treating Patients With Advanced Melanoma With BRAF Non-V600 Mutations Trametinib in Treating Patients With Advanced Melanoma With BRAF Non-V600 Mutations MGH Open DG
NCT02219724 A Phase I, Open-Label Study of MOXR0916 in Patients With Locally Advanced or Metastatic Solid Tumors A Phase I, Open-Label Study of MOXR0916 in Patients With Locally Advanced or Metastatic Solid Tumors 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
Trial Status: Showing Results: 1-10 of 22 Per Page:
123Next »
Our Melanoma Team

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