Colorectal Cancer, FGFR 1, 2, 3 and 4

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Expand Collapse Colorectal Cancer  - General Description Colorectal Cancer (CRC) is cancer that initiates in the colon or rectum-the lower part of the digestive system in the body. During digestion, food moves through the stomach and small intestine into the colon. The colon absorbs water and nutrients from food, and stores waste matter (stool) that moves from the colon through the rectum before leaving the body.

Most CRC's and rectal cancers are adenocarcinomas, meaning that they originate in cells that make and release mucus and other fluids. CRC often begins as a growth called a polyp, which may form on the inner wall of the colon or rectum. Over time, some polyps become cancerous. This highlights the importance of colonoscopy screening to find and remove polyps before they become cancerous.

CRC is the fourth most common type of cancer diagnosed in the U.S. Deaths from CRC have decreased with the use of colonoscopies and fecal occult blood tests, which check for blood in the stool. Disparities in survival have been observed between African American and other populations. This may be due to factors such as access to colonoscopy screening, or to other factors not yet identified.

Because of its prevalence, scientists have studied CRC extensively, even creating models of how cancer develops using CRC as an example. There are also families with a very high incidence of CRC occurrence. When these families were studied, certain conditions that create instability in the whole genome were identified that predispose people to CRC. These include what is called the Chromosomal Instability pathway (CIN), as well as MicroSatellite Instability pathway (MSI). These can also occur as spontaneous (uninherited) conditions in some patients. Between 6-10% of CRC's are found to have MSI. Some CRC tumors have been found to have a lot of mutations, or as physicians call it, a "very high mutational load". Some also express a ligand called PD-L1.

These are now recognized features of some CRC's, and immunological treatments may be recommended in these cases. MGH has one of the most extensive Immuno-oncology clinical trials portfolios of any US hospital. Testing for features such as CIN, MSI, a high mutational burden, and the expression of PD-L1 can be conducted at the MGH genetics laboratory, as well as at other large academic centers. Genetic instability such as CIN or MSI lead to the activation of oncogenes such as KRAS, and the inactivation of tumor suppressors such as PTEN, both of which promote tumor growth.

Other genetic alterations in how the DNA in cells is organized have been found to contribute to CRC in families and individuals. These are called epigenetic changes. Normal DNA has methyl groups added in specific regions that regulate gene expression. When the genes that suppress growth-called tumor suppressors-are methylated abnormally, this prevents the production of tumor suppressor proteins important in controlling or stopping cell growth. When tumor suppressor genes are missing, unregulated growth occurs, contributing to the development of cancer. Some tumor suppressor proteins that are frequently inactivated in CRC are APC, TP53, or loss of one arm of chromosome 18 that contains a tumor suppressor.

The study of families with a high prevalence of CRC have lead scientists to discover genetic changes that contribute to the development of CRC in sporadic cases occurring in patients. Mutations in the genes encoding the following proteins have now been associated with subsets of CRC; ALK, AKT, APC, beta-catenin, BRCA1 and BRCA2, BRAF, EGFR, ERBB2 (HER2), ERBB3 (HER3), IDH2, KRAS, MET, NRAS, PI3K, ROS, PTEN, SMO,TP53, TRK 1, 2 and 3, and others that are still being identified. Information on these specific genes is available on this website if you select the gene you want to know more about.

Distinct familial syndromes of CRC such as Lynch syndrome have been studied in patients, leading to the identification of other mechanisms contributing to the development of cancer. Before a cell can divide into two daughter cells, DNA has to be replicated so both daughter cells will have a full complement of chromosomes. DNA replication requires an enzyme called DNA Polymerase. DNA Polymerase occasionally makes errors while it is replicating DNA. Cells therefore have a "proof-reading" process that detects mistakes when they occur during DNA replication. DNA Polymerase mistakes mean that incorrect nucleotides have been incorporated into the DNA, causing mutations. Mistakes in the DNA sequence are repaired in a process called mismatch repair (MMR).
MMR involves a complex of multiple proteins. In Lynch syndrome, one or more of the proteins involved in MMR is mutated, and the mistakes in the DNA do not get corrected. Mutations in MMR proteins are not only found in familial cases of CRC, but also in patients with sporadic (non-inherited) CRC. Defects in MMR also contribute to microsatellite instability (MIS), described above. The accumulation of these mutations can lead to cancer.

The importance of accurately replicating DNA following various types of mistakes or damage is reflected in the multiple pathways cells have for correcting or repairing broken DNA. Actual breaks in the DNA strands can happen due to exposure to radiation or other DNA damaging agents. In the case of the occurrence of breaks in DNA, there are also mechanisms for detecting these breaks. Double strand breaks (DSB's) in the DNA can be repaired via several mechanisms, including Non-Homologous End Joining (NHEJ) or Homologous Repair (HR). Many proteins are involved in DSB repair. Mutations in any of the many proteins involved in either of these repair pathways (see BRCA1 and BRCA2 genes) lead to damaged DNA, which results in DNA that is incorrectly replicated, causing mutations that contribute to the development of cancer. DNA repair machinery in the cell is important in keeping the genome stable and accurate.

Testing for the mutations and genomic conditions that contribute to the development or progression of CRC is available at MGH in the sophisticated CLIA certified genomic testing lab, and in other large Centers and some private testing companies used by physicians. Validated treatments, Immune therpies, as well as clinical trials investigating improved targeted and immunologic therapies are available to patients at MGH.

NIH/NCI Cancer Website www.cancer.gov 2017

Colorectal Cancer (CRC) is cancer that initiates in the colon or rectum-the lower part of the digestive system in the body. During digestion, food moves through the stomach and small intestine into the colon. The colon absorbs water and nutrients from food, and stores waste matter (stool) that moves from the colon through the rectum before leaving the body.

Most CRC's and rectal cancers are adenocarcinomas, meaning that they originate in cells that make and release mucus and other fluids. CRC often begins as a growth called a polyp, which may form on the inner wall of the colon or rectum. Over time, some polyps become cancerous. This highlights the importance of colonoscopy screening to find and remove polyps before they become cancerous.

CRC is the fourth most common type of cancer diagnosed in the U.S. Deaths from CRC have decreased with the use of colonoscopies and fecal occult blood tests, which check for blood in the stool. Disparities in survival have been observed between African American and other populations. This may be due to factors such as access to colonoscopy screening, or to other factors not yet identified.

Because of its prevalence, scientists have studied CRC extensively, even creating models of how cancer develops using CRC as an example. There are also families with a very high incidence of CRC occurrence. When these families were studied, certain conditions that create instability in the whole genome were identified that predispose people to CRC. These include what is called the Chromosomal Instability pathway (CIN), as well as MicroSatellite Instability pathway (MSI). These can also occur as spontaneous (uninherited) conditions in some patients. Between 6-10% of CRC's are found to have MSI. Some CRC tumors have been found to have a lot of mutations, or as physicians call it, a "very high mutational load". Some also express a ligand called PD-L1.

These are now recognized features of some CRC's, and immunological treatments may be recommended in these cases. MGH has one of the most extensive Immuno-oncology clinical trials portfolios of any US hospital. Testing for features such as CIN, MSI, a high mutational burden, and the expression of PD-L1 can be conducted at the MGH genetics laboratory, as well as at other large academic centers. Genetic instability such as CIN or MSI lead to the activation of oncogenes such as KRAS, and the inactivation of tumor suppressors such as PTEN, both of which promote tumor growth.

Other genetic alterations in how the DNA in cells is organized have been found to contribute to CRC in families and individuals. These are called epigenetic changes. Normal DNA has methyl groups added in specific regions that regulate gene expression. When the genes that suppress growth-called tumor suppressors-are methylated abnormally, this prevents the production of tumor suppressor proteins important in controlling or stopping cell growth. When tumor suppressor genes are missing, unregulated growth occurs, contributing to the development of cancer. Some tumor suppressor proteins that are frequently inactivated in CRC are APC, TP53, or loss of one arm of chromosome 18 that contains a tumor suppressor.

The study of families with a high prevalence of CRC have lead scientists to discover genetic changes that contribute to the development of CRC in sporadic cases occurring in patients. Mutations in the genes encoding the following proteins have now been associated with subsets of CRC; ALK, AKT, APC, beta-catenin, BRCA1 and BRCA2, BRAF, EGFR, ERBB2 (HER2), ERBB3 (HER3), IDH2, KRAS, MET, NRAS, PI3K, ROS, PTEN, SMO,TP53, TRK 1, 2 and 3, and others that are still being identified. Information on these specific genes is available on this website if you select the gene you want to know more about.

Distinct familial syndromes of CRC such as Lynch syndrome have been studied in patients, leading to the identification of other mechanisms contributing to the development of cancer. Before a cell can divide into two daughter cells, DNA has to be replicated so both daughter cells will have a full complement of chromosomes. DNA replication requires an enzyme called DNA Polymerase. DNA Polymerase occasionally makes errors while it is replicating DNA. Cells therefore have a "proof-reading" process that detects mistakes when they occur during DNA replication. DNA Polymerase mistakes mean that incorrect nucleotides have been incorporated into the DNA, causing mutations. Mistakes in the DNA sequence are repaired in a process called mismatch repair (MMR).
MMR involves a complex of multiple proteins. In Lynch syndrome, one or more of the proteins involved in MMR is mutated, and the mistakes in the DNA do not get corrected. Mutations in MMR proteins are not only found in familial cases of CRC, but also in patients with sporadic (non-inherited) CRC. Defects in MMR also contribute to microsatellite instability (MIS), described above. The accumulation of these mutations can lead to cancer.

The importance of accurately replicating DNA following various types of mistakes or damage is reflected in the multiple pathways cells have for correcting or repairing broken DNA. Actual breaks in the DNA strands can happen due to exposure to radiation or other DNA damaging agents. In the case of the occurrence of breaks in DNA, there are also mechanisms for detecting these breaks. Double strand breaks (DSB's) in the DNA can be repaired via several mechanisms, including Non-Homologous End Joining (NHEJ) or Homologous Repair (HR). Many proteins are involved in DSB repair. Mutations in any of the many proteins involved in either of these repair pathways (see BRCA1 and BRCA2 genes) lead to damaged DNA, which results in DNA that is incorrectly replicated, causing mutations that contribute to the development of cancer. DNA repair machinery in the cell is important in keeping the genome stable and accurate.

Testing for the mutations and genomic conditions that contribute to the development or progression of CRC is available at MGH in the sophisticated CLIA certified genomic testing lab, and in other large Centers and some private testing companies used by physicians. Validated treatments, Immune therpies, as well as clinical trials investigating improved targeted and immunologic therapies are available to patients at MGH.

NIH/NCI Cancer Website www.cancer.gov 2017

Colorectal Cancer (CRC) is cancer that initiates in the colon or rectum-the lower part of the digestive system in the body. During digestion, food moves through the stomach and small intestine into the colon. The colon absorbs water and nutrients from food, and stores waste matter (stool) that moves from the colon through the rectum before leaving the body.

Most CRC's and rectal cancers are adenocarcinomas, meaning that they originate in cells that make and release mucus and other fluids. CRC often begins as a growth called a polyp, which may form on the inner wall of the colon or rectum. Over time, some polyps become cancerous. This highlights the importance of colonoscopy screening to find and remove polyps before they become cancerous.

CRC is the fourth most common type of cancer diagnosed in the U.S. Deaths from CRC have decreased with the use of colonoscopies and fecal occult blood tests, which check for blood in the stool. Disparities in survival have been observed between African American and other populations. This may be due to factors such as access to colonoscopy screening, or to other factors not yet identified.

Because of its prevalence, scientists have studied CRC extensively, even creating models of how cancer develops using CRC as an example. There are also families with a very high incidence of CRC occurrence. When these families were studied, certain conditions that create instability in the whole genome were identified that predispose people to CRC. These include what is called the Chromosomal Instability pathway (CIN), as well as MicroSatellite Instability pathway (MSI). These can also occur as spontaneous (uninherited) conditions in some patients. Between 6-10% of CRC's are found to have MSI. Some CRC tumors have been found to have a lot of mutations, or as physicians call it, a "very high mutational load". Some also express a ligand called PD-L1.

These are now recognized features of some CRC's, and immunological treatments may be recommended in these cases. MGH has one of the most extensive Immuno-oncology clinical trials portfolios of any US hospital. Testing for features such as CIN, MSI, a high mutational burden, and the expression of PD-L1 can be conducted at the MGH genetics laboratory, as well as at other large academic centers. Genetic instability such as CIN or MSI lead to the activation of oncogenes such as KRAS, and the inactivation of tumor suppressors such as PTEN, both of which promote tumor growth.

Other genetic alterations in how the DNA in cells is organized have been found to contribute to CRC in families and individuals. These are called epigenetic changes. Normal DNA has methyl groups added in specific regions that regulate gene expression. When the genes that suppress growth-called tumor suppressors-are methylated abnormally, this prevents the production of tumor suppressor proteins important in controlling or stopping cell growth. When tumor suppressor genes are missing, unregulated growth occurs, contributing to the development of cancer. Some tumor suppressor proteins that are frequently inactivated in CRC are APC, TP53, or loss of one arm of chromosome 18 that contains a tumor suppressor.

The study of families with a high prevalence of CRC have lead scientists to discover genetic changes that contribute to the development of CRC in sporadic cases occurring in patients. Mutations in the genes encoding the following proteins have now been associated with subsets of CRC; ALK, AKT, APC, beta-catenin, BRCA1 and BRCA2, BRAF, EGFR, ERBB2 (HER2), ERBB3 (HER3), IDH2, KRAS, MET, NRAS, PI3K, ROS, PTEN, SMO,TP53, TRK 1, 2 and 3, and others that are still being identified. Information on these specific genes is available on this website if you select the gene you want to know more about.

Distinct familial syndromes of CRC such as Lynch syndrome have been studied in patients, leading to the identification of other mechanisms contributing to the development of cancer. Before a cell can divide into two daughter cells, DNA has to be replicated so both daughter cells will have a full complement of chromosomes. DNA replication requires an enzyme called DNA Polymerase. DNA Polymerase occasionally makes errors while it is replicating DNA. Cells therefore have a "proof-reading" process that detects mistakes when they occur during DNA replication. DNA Polymerase mistakes mean that incorrect nucleotides have been incorporated into the DNA, causing mutations. Mistakes in the DNA sequence are repaired in a process called mismatch repair (MMR).
MMR involves a complex of multiple proteins. In Lynch syndrome, one or more of the proteins involved in MMR is mutated, and the mistakes in the DNA do not get corrected. Mutations in MMR proteins are not only found in familial cases of CRC, but also in patients with sporadic (non-inherited) CRC. Defects in MMR also contribute to microsatellite instability (MIS), described above. The accumulation of these mutations can lead to cancer.

The importance of accurately replicating DNA following various types of mistakes or damage is reflected in the multiple pathways cells have for correcting or repairing broken DNA. Actual breaks in the DNA strands can happen due to exposure to radiation or other DNA damaging agents. In the case of the occurrence of breaks in DNA, there are also mechanisms for detecting these breaks. Double strand breaks (DSB's) in the DNA can be repaired via several mechanisms, including Non-Homologous End Joining (NHEJ) or Homologous Repair (HR). Many proteins are involved in DSB repair. Mutations in any of the many proteins involved in either of these repair pathways (see BRCA1 and BRCA2 genes) lead to damaged DNA, which results in DNA that is incorrectly replicated, causing mutations that contribute to the development of cancer. DNA repair machinery in the cell is important in keeping the genome stable and accurate.

Testing for the mutations and genomic conditions that contribute to the development or progression of CRC is available at MGH in the sophisticated CLIA certified genomic testing lab, and in other large Centers and some private testing companies used by physicians. Validated treatments, Immune therpies, as well as clinical trials investigating improved targeted and immunologic therapies are available to patients at MGH.

NIH/NCI Cancer Website www.cancer.gov 2017

Colorectal Cancer (CRC) is cancer that initiates in the colon or rectum-the lower part of the digestive system in the body. During digestion, food moves through the stomach and small intestine into the colon. The colon absorbs water and nutrients from food, and stores waste matter (stool) that moves from the colon through the rectum before leaving the body.

Most CRC's and rectal cancers are adenocarcinomas, meaning that they originate in cells that make and release mucus and other fluids. CRC often begins as a growth called a polyp, which may form on the inner wall of the colon or rectum. Over time, some polyps become cancerous. This highlights the importance of colonoscopy screening to find and remove polyps before they become cancerous.

CRC is the fourth most common type of cancer diagnosed in the U.S. Deaths from CRC have decreased with the use of colonoscopies and fecal occult blood tests, which check for blood in the stool. Disparities in survival have been observed between African American and other populations. This may be due to factors such as access to colonoscopy screening, or to other factors not yet identified.

Because of its prevalence, scientists have studied CRC extensively, even creating models of how cancer develops using CRC as an example. There are also families with a very high incidence of CRC occurrence. When these families were studied, certain conditions that create instability in the whole genome were identified that predispose people to CRC. These include what is called the Chromosomal Instability pathway (CIN), as well as MicroSatellite Instability pathway (MSI). These can also occur as spontaneous (uninherited) conditions in some patients. Between 6-10% of CRC's are found to have MSI. Some CRC tumors have been found to have a lot of mutations, or as physicians call it, a "very high mutational load". Some also express a ligand called PD-L1.

These are now recognized features of some CRC's, and immunological treatments may be recommended in these cases. MGH has one of the most extensive Immuno-oncology clinical trials portfolios of any US hospital. Testing for features such as CIN, MSI, a high mutational burden, and the expression of PD-L1 can be conducted at the MGH genetics laboratory, as well as at other large academic centers. Genetic instability such as CIN or MSI lead to the activation of oncogenes such as KRAS, and the inactivation of tumor suppressors such as PTEN, both of which promote tumor growth.

Other genetic alterations in how the DNA in cells is organized have been found to contribute to CRC in families and individuals. These are called epigenetic changes. Normal DNA has methyl groups added in specific regions that regulate gene expression. When the genes that suppress growth-called tumor suppressors-are methylated abnormally, this prevents the production of tumor suppressor proteins important in controlling or stopping cell growth. When tumor suppressor genes are missing, unregulated growth occurs, contributing to the development of cancer. Some tumor suppressor proteins that are frequently inactivated in CRC are APC, TP53, or loss of one arm of chromosome 18 that contains a tumor suppressor.

The study of families with a high prevalence of CRC have lead scientists to discover genetic changes that contribute to the development of CRC in sporadic cases occurring in patients. Mutations in the genes encoding the following proteins have now been associated with subsets of CRC; ALK, AKT, APC, beta-catenin, BRCA1 and BRCA2, BRAF, EGFR, ERBB2 (HER2), ERBB3 (HER3), IDH2, KRAS, MET, NRAS, PI3K, ROS, PTEN, SMO,TP53, TRK 1, 2 and 3, and others that are still being identified. Information on these specific genes is available on this website if you select the gene you want to know more about.

Distinct familial syndromes of CRC such as Lynch syndrome have been studied in patients, leading to the identification of other mechanisms contributing to the development of cancer. Before a cell can divide into two daughter cells, DNA has to be replicated so both daughter cells will have a full complement of chromosomes. DNA replication requires an enzyme called DNA Polymerase. DNA Polymerase occasionally makes errors while it is replicating DNA. Cells therefore have a "proof-reading" process that detects mistakes when they occur during DNA replication. DNA Polymerase mistakes mean that incorrect nucleotides have been incorporated into the DNA, causing mutations. Mistakes in the DNA sequence are repaired in a process called mismatch repair (MMR).
MMR involves a complex of multiple proteins. In Lynch syndrome, one or more of the proteins involved in MMR is mutated, and the mistakes in the DNA do not get corrected. Mutations in MMR proteins are not only found in familial cases of CRC, but also in patients with sporadic (non-inherited) CRC. Defects in MMR also contribute to microsatellite instability (MIS), described above. The accumulation of these mutations can lead to cancer.

The importance of accurately replicating DNA following various types of mistakes or damage is reflected in the multiple pathways cells have for correcting or repairing broken DNA. Actual breaks in the DNA strands can happen due to exposure to radiation or other DNA damaging agents. In the case of the occurrence of breaks in DNA, there are also mechanisms for detecting these breaks. Double strand breaks (DSB's) in the DNA can be repaired via several mechanisms, including Non-Homologous End Joining (NHEJ) or Homologous Repair (HR). Many proteins are involved in DSB repair. Mutations in any of the many proteins involved in either of these repair pathways (see BRCA1 and BRCA2 genes) lead to damaged DNA, which results in DNA that is incorrectly replicated, causing mutations that contribute to the development of cancer. DNA repair machinery in the cell is important in keeping the genome stable and accurate.

Testing for the mutations and genomic conditions that contribute to the development or progression of CRC is available at MGH in the sophisticated CLIA certified genomic testing lab, and in other large Centers and some private testing companies used by physicians. Validated treatments, Immune therpies, as well as clinical trials investigating improved targeted and immunologic therapies are available to patients at MGH.

NIH/NCI Cancer Website www.cancer.gov 2017

PubMed ID's
2188735, 23897299, 20965415
Expand Collapse FGFR 1, 2, 3 and 4  - General Description
CLICK IMAGE FOR MORE INFORMATION
Fibroblast growth factors (FGF’s) are ligands that bind to FGF cell surface receptors (FGFR’s) and activate them. Once activated, FGFR’s on normal cells transmit a growth signal inside the cell. This growth signal is transmitted via two important pathways inside cells; the RAS-dependent MAP kinase pathway, and a second signal pathway that involves PI3K and AKT. There are four different FGFR’s that make up a family of FGFR tyrosine kinase cell surface receptors, each having an extracellular domain that binds FGF ligands, a second domain that goes through the cell outer membrane, and a third domain that is inside the cell cytoplasm (see diagram above). FGFR signaling in normal cells stimulates proliferation, differentiation, embryonic development, cell migration, survival, angiogenesis (vascularization), and organogenesis (organ development).

Recently, FGFR genetic abnormalities have been found in several types of cancer. There are four FGFR family members, FGFR1, FGFR2, FGFR3, and FGFR4. Alterations in FGFR genes result in dysregulated FGF receptors and can promote cancer growth and metastasis. In a recent study of almost 5000 tumors, alterations in FGFR were found in 7% of of tumors. Among these tumors, alterations were identified in all 4 FGFR’s including FGFR1 (49%), FGFR2 (19%), FGFR3 (23%), and FGFR4 (7%). A small number of the tumors had genetic alterations in more than one type of FGFR. Clearly cancers have found a way to take advantage of FGF/FGFR signaling pathway in cells to cause uncontrolled growth leading to tumors.

While the FGFR genetic abnormalities may vary in frequency depending on the group of tumor types tested, there are clearly some patterns emerging in terms of which tumor types are likely to have specific kinds of genetic alterations in FGFR 1, 2, 3 or 4. Genetic alterations in the FGFR receptors can include point mutations, insertions/deletions, gene amplification, or translocations. The sensitivity of various gene alterations to FGFR inhibition is currently under investigation. Drugs targeting the FGF/FGFR pathway include small molecule tyrosine kinases inhibitors and ligand traps.

Several pharmaceutical companies have developed drugs that target and inhibit FGFR in tumors. Some of these are designed to target multiple members of the FGFR family. At MGH and other major cancer centers, clinical trials are available to patients whose tumors have been tested and found to have genetically altered FGFR. Treatment for these patients can be available on clinical studies testing these FGFR inhibitors, including FGFR inhibitors called TAS120 and Debio 1347. Other agents such as FGF401 and BLU554 are specific for inhibiting FGFR4 and are being tested in liver cancer. Contact the MGH Cancer Center to find out more about having genetic testing performed on a tumor, or for more information about these clinical trials.

Fibroblast growth factors (FGF’s) are ligands that bind to FGF cell surface receptors (FGFR’s) and activate them. Once activated, FGFR’s on normal cells transmit a growth signal inside the cell. This growth signal is transmitted via two important pathways inside cells; the RAS-dependent MAP kinase pathway, and a second signal pathway that involves PI3K and AKT. There are four different FGFR’s that make up a family of FGFR tyrosine kinase cell surface receptors, each having an extracellular domain that binds FGF ligands, a second domain that goes through the cell outer membrane, and a third domain that is inside the cell cytoplasm (see diagram above). FGFR signaling in normal cells stimulates proliferation, differentiation, embryonic development, cell migration, survival, angiogenesis (vascularization), and organogenesis (organ development).

Recently, FGFR genetic abnormalities have been found in several types of cancer. There are four FGFR family members, FGFR1, FGFR2, FGFR3, and FGFR4. Alterations in FGFR genes result in dysregulated FGF receptors and can promote cancer growth and metastasis. In a recent study of almost 5000 tumors, alterations in FGFR were found in 7% of of tumors. Among these tumors, alterations were identified in all 4 FGFR’s including FGFR1 (49%), FGFR2 (19%), FGFR3 (23%), and FGFR4 (7%). A small number of the tumors had genetic alterations in more than one type of FGFR. Clearly cancers have found a way to take advantage of FGF/FGFR signaling pathway in cells to cause uncontrolled growth leading to tumors.

While the FGFR genetic abnormalities may vary in frequency depending on the group of tumor types tested, there are clearly some patterns emerging in terms of which tumor types are likely to have specific kinds of genetic alterations in FGFR 1, 2, 3 or 4. Genetic alterations in the FGFR receptors can include point mutations, insertions/deletions, gene amplification, or translocations. The sensitivity of various gene alterations to FGFR inhibition is currently under investigation. Drugs targeting the FGF/FGFR pathway include small molecule tyrosine kinases inhibitors and ligand traps.

Several pharmaceutical companies have developed drugs that target and inhibit FGFR in tumors. Some of these are designed to target multiple members of the FGFR family. At MGH and other major cancer centers, clinical trials are available to patients whose tumors have been tested and found to have genetically altered FGFR. Treatment for these patients can be available on clinical studies testing these FGFR inhibitors, including FGFR inhibitors called TAS120 and Debio 1347. Other agents such as FGF401 and BLU554 are specific for inhibiting FGFR4 and are being tested in liver cancer. Contact the MGH Cancer Center to find out more about having genetic testing performed on a tumor, or for more information about these clinical trials.

PubMed ID's
9212826, 24265351
Expand Collapse FGFR 1, 2, 3 and 4  in Colorectal Cancer
Genetic alterations in FGFR family members have been found in colorectal cancers. FGFR2 has been found to be mutated in some tumors. In rare cases, FGF4 has been found to be amplified.



Genetic alterations in FGFR family members have been found in colorectal cancers. FGFR2 has been found to be mutated in some tumors. In rare cases, FGF4 has been found to be amplified.



PubMed ID's
24265351
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 Colorectal Cancer Team

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Your Matched Clinical Trials

Trial Matches: (D) - Disease, (G) - Gene
Trial Status: Showing Results: 1-10 of 39 Per Page:
1234Next »
Protocol # Title Location Status Match
NCT01948297 Debio 1347-101 Phase I Trial in Advanced Solid Tumours With Fibroblast Growth Factor Receptor (FGFR) Alterations Debio 1347-101 Phase I Trial in Advanced Solid Tumours With Fibroblast Growth Factor Receptor (FGFR) Alterations MGH Open DG
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
NCT02715284 A Phase 1 Dose Escalation and Cohort Expansion Study of TSR-042, an Anti-PD-1 Monoclonal Antibody, in Patients With Advanced Solid Tumors A Phase 1 Dose Escalation and Cohort Expansion Study of TSR-042, an Anti-PD-1 Monoclonal Antibody, in Patients With Advanced Solid Tumors 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
NCT03057509 A Pilot Study Of Ga-68-DOTA-TOC Imaging In Participants With Small Bowel Carcinoid Tumors A Pilot Study Of Ga-68-DOTA-TOC Imaging In Participants With Small Bowel Carcinoid Tumors MGH Open D
NCT02099058 A Study Evaluating the Safety, Pharmacokinetics (PK), and Preliminary Efficacy of ABBV-399 in Subjects With Advanced Solid Tumors. A Study Evaluating the Safety, Pharmacokinetics (PK), and Preliminary Efficacy of ABBV-399 in Subjects With Advanced Solid Tumors. MGH Open D
NCT02908451 A Study of AbGn-107 in Patients With Gastric, Colorectal, or Pancreatic Cancer A Study of AbGn-107 in Patients With Gastric, Colorectal, or Pancreatic Cancer 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
NCT01351103 A Study of LGK974 in Patients With Malignancies Dependent on Wnt Ligands A Study of LGK974 in Patients With Malignancies Dependent on Wnt Ligands MGH Open D
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 D
Trial Status: Showing Results: 1-10 of 39 Per Page:
1234Next »
Our Colorectal Cancer Team

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