Gall Bladder and Bile Duct Cancers, FGFR2

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Expand Collapse Gall Bladder and Bile Duct Cancers  - General Description Gallbladder cancer and bile duct cancer arise in specific areas of the biliary tract. As a group, they are fairly rare, accounting for only 3% of gastrointestinal malignancies. Standard therapy involving surgery and/or chemotherapy can be effective if the disease is detected early. However, recurrent or advanced disease has been challenging to treat.

There have been significant advances in our understanding of the underlying mechanisms of cancer development in biliary tract cancers, particularly those arising in the bile duct. Cholangiocarcinoma is the more common name for bile duct cancer and can occur either inside the liver (intrahepatic cholangiocarcinoma) or in the part of the bile duct that lies outside the liver (extrahapatic cholangiocarcinoma). The incidence of cholangiocarcinoma is rising worldwide, possibly due to an increasing incidence of hepatitis B and hepatitis C infection that can cause cirrhosis of the liver.

Ongoing research has identified new potential directions for targeted therapy in cholangiocarcinoma. Researchers at the MGH discovered a subset of patients with intrahepatic cholangiocarcinoma that have a mutation in a gene called IDH (isocitrate dehydrogenase). This mutation alters the normal activity of the enzyme encoded by this gene, with the resulting production of a new metabolite (2-hydroxyglutarate, or 2-HG). This 2-HG metabolite accumulates to very high levels in the tumor cells and alters how the tumor cell reads a subset of important genes in the DNA (epigenetic regulation). Furthermore, in a different subset of cholangiocarcinoma patients, a chromosomal abnormality in the gene FGFR2 has been identified. This abnormality is a fusion between part of the FGFR2 gene to part of another gene. The result is a cancer protein that constantly activates oncogenic FGFR2 signaling. The clinical utility of therapeutically targeting these tumor alterations are topics of current clinical trial investigations.

Gallbladder cancer and bile duct cancer arise in specific areas of the biliary tract. As a group, they are fairly rare, accounting for only 3% of gastrointestinal malignancies. Standard therapy involving surgery and/or chemotherapy can be effective if the disease is detected early. However, recurrent or advanced disease has been challenging to treat.

There have been significant advances in our understanding of the underlying mechanisms of carcinogenesis in biliary tract cancers, particularly those arising in the bile duct. Cholangiocarcinoma is the more common name for bile duct cancer and can occur either inside the liver (intrahepatic cholangiocarcinoma) or in the part of the bile duct that lies outside the liver (extrahapatic cholangiocarcinoma). The incidence of cholangiocarcinoma is rising worldwide, possibly due to an increasing incidence of hepatitis B and hepatitis C infection that can cause cirrhosis of the liver.

Ongoing research has identified new potential directions for targeted therapy in cholangiocarcinoma. Researchers at the MGH discovered a subset of patients with intrahepatic cholangiocarcinoma that harbor a mutation in a gene called IDH (isocitrate dehydrogenase). This alters the normal activity of the enzyme encoded by this gene, thereby producing a new metabolite (2-hydroxyglutarate, or 2-HG). This metabolite accumulates to very high levels in the tumor cells and alters how the tumor cell reads a subset of important genes (epigenetic regulation). Furthermore, a chromosomal abnormality in the gene FGFR2 has been identified in a subset of cholangiocarcinoma patients. This abnormality is a fusion between part of the FGFR2 gene to part of one of several other genes. The result is a cancer protein that constantly activates oncogenic FGFR2 signaling. The clinical utility of therapeutically targeting these tumor alterations are topics of current clinical trial investigations.

Gallbladder cancer and bile duct cancer arise in specific areas of the biliary tract. As a group, they are fairly rare, accounting for only 3% of gastrointestinal malignancies. Standard therapy involving surgery and/or chemotherapy can be effective if the disease is detected early. However, recurrent or advanced disease has been challenging to treat.

There have been significant advances in our understanding of the underlying mechanisms of cancer development in biliary tract cancers, particularly those arising in the bile duct. Cholangiocarcinoma is the more common name for bile duct cancer and can occur either inside the liver (intrahepatic cholangiocarcinoma) or in the part of the bile duct that lies outside the liver (extrahapatic cholangiocarcinoma). The incidence of cholangiocarcinoma is rising worldwide, possibly due to an increasing incidence of hepatitis B and hepatitis C infection that can cause cirrhosis of the liver.

Ongoing research has identified new potential directions for targeted therapy in cholangiocarcinoma. Researchers at the MGH discovered a subset of patients with intrahepatic cholangiocarcinoma that have a mutation in a gene called IDH (isocitrate dehydrogenase). This mutation alters the normal activity of the enzyme encoded by this gene, with the resulting production of a new metabolite (2-hydroxyglutarate, or 2-HG). This 2-HG metabolite accumulates to very high levels in the tumor cells and alters how the tumor cell reads a subset of important genes in the DNA (epigenetic regulation). Furthermore, in a different subset of cholangiocarcinoma patients, a chromosomal abnormality in the gene FGFR2 has been identified. This abnormality is a fusion between part of the FGFR2 gene to part of another gene. The result is a cancer protein that constantly activates oncogenic FGFR2 signaling. The clinical utility of therapeutically targeting these tumor alterations are topics of current clinical trial investigations.

Gallbladder cancer and bile duct cancer arise in specific areas of the biliary tract. As a group, they are fairly rare, accounting for only 3% of gastrointestinal malignancies. Standard therapy involving surgery and/or chemotherapy can be effective if the disease is detected early. However, recurrent or advanced disease has been challenging to treat.

There have been significant advances in our understanding of the underlying mechanisms of carcinogenesis in biliary tract cancers, particularly those arising in the bile duct. Cholangiocarcinoma is the more common name for bile duct cancer and can occur either inside the liver (intrahepatic cholangiocarcinoma) or in the part of the bile duct that lies outside the liver (extrahapatic cholangiocarcinoma). The incidence of cholangiocarcinoma is rising worldwide, possibly due to an increasing incidence of hepatitis B and hepatitis C infection that can cause cirrhosis of the liver.

Ongoing research has identified new potential directions for targeted therapy in cholangiocarcinoma. Researchers at the MGH discovered a subset of patients with intrahepatic cholangiocarcinoma that harbor a mutation in a gene called IDH (isocitrate dehydrogenase). This alters the normal activity of the enzyme encoded by this gene, thereby producing a new metabolite (2-hydroxyglutarate, or 2-HG). This metabolite accumulates to very high levels in the tumor cells and alters how the tumor cell reads a subset of important genes (epigenetic regulation). Furthermore, a chromosomal abnormality in the gene FGFR2 has been identified in a subset of cholangiocarcinoma patients. This abnormality is a fusion between part of the FGFR2 gene to part of one of several other genes. The result is a cancer protein that constantly activates oncogenic FGFR2 signaling. The clinical utility of therapeutically targeting these tumor alterations are topics of current clinical trial investigations.

PubMed ID's
2083573, 20375404, 23558953, 25384085, 25608663
Expand Collapse FGFR2  - General Description
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FGFR is a gene that provides the code for making a protein called fibroblast growth factor receptor. This receptor is located on the surface of cells. FGFR has at least 4 subtypes, FGFR 1,2,3, and 4. When certain growth factors (proteins that stimulate cell growth and division) bind to an FGFR receptor, this activates a signaling system within the cell that causes the cell to undergo certain changes. In their normal role, the FGFR proteins play crucial roles in cell proliferation, migration, angiogenesis, and survival.

In certain types of cancers, genetic changes in the FGFR gene have been found. These changes include either amplification (more of the receptor is made than in normal cells), translocation (the gene has moved position such that it is under different regulation, causing more of the receptor to be made than in normal cells), or mutation (changes in the DNA that result in dysregulation of the protein, usually causing continuous activation of the receptor, even in the absence of growth factor). The excessive signaling that results from these genetic changes in number or activity level of the FGFR receptors contribute to abnormal cell growth and cancer. Unusual expression of the FGFR2 gene from various gene alterations has been found in some Breast cancers, Bladder cancers, Colorectal cancers, Esophageal/Gastric cancers, Endometrial cancers, Gall Bladder and Bile Duct (Cholangiocarcinoma) cancers, Glioblastomas, Head and Neck cancers, Lung cancers, Ovarian cancers, Pancreatic cancer, and Prostate cancer.

Preclinical testing in cancer cell lines suggest that FGFR gene alterations can be an important mechanism of tumor progression that may be effectively targeted with FGFR inhibitors. This has led to the development of clinical trials evaluating FGFR inhibitors in FGFR genetically altered tumors, with treatment of patients in these early studies underway.

FGFR is a gene that provides the code for making a protein called fibroblast growth factor receptor. This receptor is located on the surface of cells. FGFR has at least 4 subtypes, FGFR 1,2,3, and 4. When certain growth factors (proteins that stimulate cell growth and division) bind to an FGFR receptor, this activates a signaling system within the cell that causes the cell to undergo certain changes. In their normal role, the FGFR proteins play crucial roles in cell proliferation, migration, angiogenesis, and survival.

In certain types of cancers, genetic changes in the FGFR gene have been found. These changes include either amplification (more of the receptor is made than in normal cells), translocation (the gene has moved position such that it is under different regulation, causing more of the receptor to be made than in normal cells), or mutation (changes in the DNA that result in dysregulation of the protein, usually causing continuous activation of the receptor, even in the absence of growth factor). The excessive signaling that results from these genetic changes in number or activity level of the FGFR receptors contribute to abnormal cell growth and cancer. Unusual expression of the FGFR2 gene from various gene alterations has been found in some Breast cancers, Bladder cancers, Colorectal cancers, Esophageal/Gastric cancers, Endometrial cancers, Gall Bladder and Bile Duct (Cholangiocarcinoma) cancers, Glioblastomas, Head and Neck cancers, Lung cancers, Ovarian cancers, Pancreatic cancer, and Prostate cancer.

Preclinical testing in cancer cell lines suggest that FGFR gene alterations can be an important mechanism of tumor progression that may be effectively targeted with FGFR inhibitors. This has led to the development of clinical trials evaluating FGFR inhibitors in FGFR genetically altered tumors, with treatment of patients in these early studies underway.

PubMed ID's
24265351
Expand Collapse FGFR2  in Gall Bladder and Bile Duct Cancers
The newest generation of genotyping platforms has recently revealed the presence of FGFR2 gene fusions in a subset of cholangiocarcinoma patients. These fusions produce a novel protein in the tumor cells that leads to constant activation of FGFR2 signaling and is thought to be an essential driver of the cancer process. New FGFR family inhibitors have been developed and there is significant interest in accruing patients with FGFR2 fusion into these early-phase clinical trials.

The newest generation of genotyping platforms has recently revealed the presence of FGFR2 gene fusions in a subset of cholangiocarcinoma patients. These fusions produce a novel protein in the tumor cells that leads to constant activation of FGFR2 signaling and is thought to be an essential driver of the cancer process. New FGFR family inhibitors have been developed and there is significant interest in accruing patients with FGFR2 fusion into these early-phase clinical trials.

PubMed ID's
24550739, PMC3958461,
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 all 6 results Per Page:
Protocol # Title Location Status Match
NCT02508467 A Phase 1 Study of BLU-554 in Patients With Hepatocellular Carcinoma A Phase 1 Study of BLU-554 in Patients With Hepatocellular Carcinoma MGH Open D
NCT02568267 Basket Study of Entrectinib (RXDX-101) for the Treatment of Patients With Solid Tumors Harboring NTRK 1/2/3 (Trk A/B/C), ROS1, or ALK Gene Rearrangements (Fusions) Basket Study of Entrectinib (RXDX-101) for the Treatment of Patients With Solid Tumors Harboring NTRK 1/2/3 (Trk A/B/C), ROS1, or ALK Gene Rearrangements (Fusions) MGH Open D
NCT02375880 Study of DKN-01 and Gemcitabine/Cisplatin in Patients With Carcinoma to Primary to the Intra- or Extra-Hepatic Biliary System or Gallbladder Study of DKN-01 and Gemcitabine/Cisplatin in Patients With Carcinoma to Primary to the Intra- or Extra-Hepatic Biliary System or Gallbladder MGH Open D
NCT02540291 Study of E7046 in Subjects With Selected Advanced Malignancies Study of E7046 in Subjects With Selected Advanced Malignancies MGH Open D
NCT02576431 Study of LOXO-101 in Subjects With NTRK Fusion Positive Solid Tumors (NAVIGATE) Study of LOXO-101 in Subjects With NTRK Fusion Positive Solid Tumors (NAVIGATE) MGH Open D
NCT02481154 Study of Orally Administered AG-881 in Patients With Advanced Solid Tumors, Including Gliomas, With an IDH1 and/or IDH2 Mutation Study of Orally Administered AG-881 in Patients With Advanced Solid Tumors, Including Gliomas, With an IDH1 and/or IDH2 Mutation MGH Open D
MGH has many open clinical trials for other cancers not shown on the Targeted Cancer Care website. They can be found on the MassGeneral.org clinical trials search page.

Additional clinical trials may be applicable to your search criteria, but they may not be available at MGH. These clinical trials can typically be found by searching the clinicaltrials.gov website.
Trial Status: Showing all 6 results Per Page:

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