Melanoma, KIT

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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 KIT  - General Description
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KIT is a gene that provides the code for making a protein belonging to the family of receptor tyrosine kinases (RTKs) that are located on the cell surface. RTKs are the first link in a chain that sends signals from the outside of a cell to the parts inside the cell that control different cellular processes, such as how cells grow and divide (proliferate), become able to perform specific tasks (differentiate) or move (migrate). The KIT protein is activated when another protein, called stem cell factor, attaches (binds) to it. The activated KIT protein then activates other proteins inside the cell, leading to activation of a series of signaling pathways.

Mutations in KIT are the most common genetic change associated with gastrointestinal stromal tumors (GISTs). GISTs are found in the gastrointestinal (GI) tract, usually in the stomach or small intestine. In most cases, these 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. The mutations create a protein that no longer needs binding of the stem cell factor protein to become activated. Therefore, the signaling systems are always turned on. The constant signaling increases proliferation of a certain type of cell (interstitial cells of Cajal [ICCs]), leading to GIST formation.

KIT mutations also are involved in some cases of acute myeloid leukemia (AML), sinonasal natural killer T-cell lymphoma (NKTCL), some types of melanoma and a type of testicular cancer (seminoma).

Source: Genetics Home Reference
The KIT gene (also known as CD117) encodes for a transmembrane receptor that binds the ligand known as stem cell factor. Binding of the ligand leads to KIT heterodimerization and then autophosphorylation through activation of its intrinsic receptor tyrosine kinase activity. These phosphorylation sites serve as docking areas for the assembly of signal transduction complexes that facilitate MAP kinase, PI3K/AKT/mTOR and JAK/STAT pathway activation to promote cellular proliferation and survival. The highest frequency of KIT mutations are found in gastrointestinal stromal tumors (85%) and core binding factor acute myeloid leukemias (46%).

Source: Genetics Home Reference
PubMed ID's
9438854, 15339674, 15948115, 16647948, 17372901, 16908931
Expand Collapse KIT  in Melanoma
The KIT D816V mutation is highly prevalent in systemic mastocytosis, where it can serve as a helpful diagnostic tool.

Accumulating evidence suggests that KIT inhibitors may be useful in the treatment of melanoma patients harboring certain oncogenic KIT mutations. In two phase II clinical trials, treatment with imatinib resulted in significant clinical responses in a subset of advanced melanoma patients with activating mutations in KIT. Response rates were better for patients harboring mutations in exons 11 and 13, within the KIT juxtamembrane domain. Additional clinical studies using KIT inhibitors in selected melanoma patient populations are currently underway. However, mutations affecting codon D816 specifically are known to confer therapeutic resistance to imatinib.

The KIT D816V mutation is highly prevalent in systemic mastocytosis, where it can serve as a helpful diagnostic tool.

Accumulating evidence suggests that KIT inhibitors may be useful in the treatment of melanoma patients harboring certain oncogenic KIT mutations. In two phase II clinical trials, treatment with imatinib resulted in significant clinical responses in a subset of advanced melanoma patients with activating mutations in KIT. Response rates were better for patients harboring mutations in exons 11 and 13, within the KIT juxtamembrane domain. Additional clinical studies using KIT inhibitors in selected melanoma patient populations are currently underway. However, mutations affecting codon D816 specifically are known to confer therapeutic resistance to imatinib.

PubMed ID's
18980976, 12932387, 21642685, 21690468
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
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 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
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 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
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 D
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
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
Trial Status: Showing Results: 1-10 of 23 Per Page:
123Next »
Our Melanoma Team

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