Melanoma, KIT

View:
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 KIT  - General Description
CLICK IMAGE FOR MORE INFORMATION
The KIT gene (also known as CD117) encodes a transmembrane receptor that binds the ligand known as stem cell factor (SCF). Binding of the ligand SCF on the outside of the cell leads to the activation of the KIT receptor tyrosine kinase inside the cell. When tyrosine kinases are activated, they become phosphorylated, meaning they have phosphate added at specific sites on the portion of the receptor that is inside the cell. These phosphorylation sites serve as docking sites for the assembly of signal proteins that then cause the activation of several signal pathways. When KIT is activated, it specifically activates the MAP kinase pathway, the PI3K/AKT/mTOR pathway, and the JAK/STAT pathway. When activated, these signal pathways promote cellular proliferation and survival.

In studies examining the KIT protein in cancers, mutations in KIT have been identified that lead to the production of an altered protein that cannot be regulated normally. Invariably, the mutated KIT protein found in tumors no longer needs SCF ligand binding to the external portion of the receptor to be activated. Instead, mutated KIT stays in a constantly activated state. This constant stimulation of growth and survival signal pathways can leads to the development of cancer. Mutations and other genetic alterations in the gene encoding KIT have been found in several tumor types. Mutations in the KIT protein are frequently found in GastroIntestinal Stromal Tumors (GIST), in some types of Acute Myeloid Leukemia (AML), in melanoma, and less frequently in some other types of tumors. Clinical trials involving KIT inhibitors, as well as KIT inhibitors used in combination with other therapeutic agents are underway at the MGH Cancer Center. Further studies are needed to prevent the growth of tumors containing KIT alterations.
The KIT gene (also known as CD117) encodes a transmembrane receptor that binds the ligand known as stem cell factor (SCF). Binding of the ligand SCF on the outside of the cell leads to the activation of the KIT receptor tyrosine kinase inside the cell. When tyrosine kinases are activated, they become phosphorylated, meaning they have phosphate added at specific sites on the portion of the receptor that is inside the cell. These phosphorylation sites serve as docking sites for the assembly of signal proteins that then cause the activation of several signal pathways. When KIT is activated, it specifically activates the MAP kinase pathway, the PI3K/AKT/mTOR pathway, and the JAK/STAT pathway. When activated, these signal pathways promote cellular proliferation and survival.

In studies examining the KIT protein in cancers, mutations in KIT have been identified that lead to the production of an altered protein that cannot be regulated normally. Invariably, the mutated KIT protein found in tumors no longer needs SCF ligand binding to the external portion of the receptor to be activated. Instead, mutated KIT stays in a constantly activated state. This constant stimulation of growth and survival signal pathways can leads to the development of cancer. Mutations and other genetic alterations in the gene encoding KIT have been found in several tumor types. Mutations in the KIT protein are frequently found in GastroIntestinal Stromal Tumors (GIST), in some types of Acute Myeloid Leukemia (AML), in melanoma, and less frequently in some other types of tumors. Clinical trials involving KIT inhibitors, as well as KIT inhibitors used in combination with other therapeutic agents are underway at the MGH Cancer Center. Further studies are needed to prevent the growth of tumors containing KIT alterations.

PubMed ID's
9438854, 15339674, 15948115, 16647948, 17372901, 16908931
Expand Collapse KIT  in Melanoma


Genetic alterations in the gene encoding the KIT protein have been found in melanoma. Mutations in exon 11 or 13 activate the protein in tumor cells, as does amplification of the gene encoding KIT or other mechanisms that result in an overabundance of the protein. Whether through mutations that alter the protein, or mechanisms causing overexpression of the protein, KIT is constantly activated, sending growth and proliferation signals to melanoma cells. Treatment with KIT inhibitors is available, as well as clinical trials studying the use of KIT inhibitors in combination with other therapeutic agents at the MGH Cancer Center.

Genetic alterations in the gene encoding the KIT protein have been found in melanoma. Mutations in exon 11 or 13 activate the protein in tumor cells, as does amplification of the gene encoding KIT or other mechanisms that result in an overabundance of the protein. Whether through mutations that alter the protein, or mechanisms causing overexpression of the protein, KIT is constantly activated, sending growth and proliferation signals to melanoma cells. Treatment with KIT inhibitors is available, as well as clinical trials studying the use of KIT inhibitors in combination with other therapeutic agents at the MGH Cancer Center.

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.
Our Melanoma Team

Share with your Physican

Print information for your Physician.

Print information

Your Matched Clinical Trials

Trial Matches: (D) - Disease, (G) - Gene
Trial Status: Showing Results: 1-10 of 49 Per Page:
12345Next »
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
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
NCT02880371 A Study of ARRY-382 in Combination With Pembrolizumab for the Treatment of Patients With Advanced Solid Tumors A Study of ARRY-382 in Combination With Pembrolizumab for the Treatment of 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
NCT03273153 A Study of Cobimetinib Plus Atezolizumab Versus Pembrolizumab in Participants With Previously Untreated Advanced BRAFv600 Wild-Type Melanoma A Study of Cobimetinib Plus Atezolizumab Versus Pembrolizumab in Participants With Previously Untreated Advanced BRAFv600 Wild-Type Melanoma MGH Open D
Trial Status: Showing Results: 1-10 of 49 Per Page:
12345Next »
Our Melanoma Team

Share with your Physican

Print information for your Physician.

Print information