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Expand Collapse Colorectal Cancer  - General Description A cancer that begins in the colon is often called colon cancer and a cancer that begins in the rectum is often called rectal cancer, but sometimes the term colorectal cancer is used for a cancer that begins in either place. This year about 132,700 people in the U.S. will be diagnosed with cancer of the colon or rectum. However, nearly 1.1 million remain alive today after having been diagnosed with colorectal cancer.

The colon and rectum are parts of the large intestine. In the colon, which accounts for most of the length of the large intestine, water and nutrients are extracted from partly-digested food before the food is turned into waste. The waste then enters the rectum before being pushed out of the body, leaving via the short anal canal and the anus (cancers also develop in the anus and anal canal, but they aren't classified as colorectal cancers). Most colon cancers and rectal cancers are adenocarcinomas, tumors that begin in gland-like cells lining the colon or rectum. Other types of cancerous tissues account for only 2% to 5% of colorectal cancers.

Colorectal cancer (and other tumors) can spread (metastasize) from the place where it started (the primary tumor) in 3 ways. First, it can invade the normal tissue surrounding it. Second, cancer cells can enter the lymph system and travel through lymph vessels to distant parts of the body. Third, the cancer cells can get into the bloodstream and go to other places in the body. In these distant places, the colon/rectal cancer cells cause secondary tumors to grow. The main sites to which colorectal cancer spreads are the liver, lungs and peritoneum. To find out whether the cancer has entered the lymph system, a surgeon removes all or part of a node near the primary tumor and a pathologist examines it to see if cancer cells are present. Several kinds of imaging also can be performed to determine if the cancer has spread. These include chest x-rays, MRI, CT scans and PET scans.

The FDA has approved several targeted therapies for treatment of patients with metastatic colorectal cancer. These include bevacizumab (Avastin), cetuximab (Erbitux), panitumumab (Vectibix) and ziv-afibercept (Zaltrap).

Despite significant improvements in the treatment of colorectal cancers, novel therapies and treatment strategies are needed.

Source: National Cancer Institute, 2015
The prognosis of patients with colon cancer is clearly related to the degree of tumor penetration through the bowel wall, the presence or absence of nodal involvement, and the presence or absence of distant metastases. These three characteristics form the basis for all staging systems developed for this disease. Bowel obstruction and bowel perforation are indicators of poor prognosis. Elevated pretreatment serum levels of carcinoembryonic antigen (CEA) have a negative prognostic significance. The American Joint Committee on Cancer and a National Cancer Institute-sponsored panel recommended that at least 12 lymph nodes be examined in patients with colon and rectal cancer to confirm the absence of nodal involvement by tumor. This recommendation takes into consideration that the number of lymph nodes examined is a reflection of the aggressiveness of lymphovascular mesenteric dissection at the time of surgical resection and the pathologic identification of nodes in the specimen. Retrospective studies demonstrated that the number of lymph nodes examined in colon and rectal surgery may be associated with patient outcome.

Many other prognostic markers have been evaluated retrospectively for patients with colon cancer, though most have not been prospectively validated (including allelic loss of chromosome 18q or thymidylate synthase expression). Microsatellite instability, also associated with hereditary nonpolyposis colon cancer (HNPCC), has been associated with improved survival (independent of tumor stage) in a population-based series of 607 patients younger than 50 years of age with colorectal cancer. Treatment decisions generally depend on factors such as physician/patient preferences and the stage of the disease, rather than the age of the patient. Racial differences in overall survival after adjuvant therapy have been observed (although not in disease-free survival), suggesting that comorbid conditions play a role in survival outcome in different patient populations.

Source: National Cancer Institute, 2012
A cancer that begins in the colon is often called colon cancer and a cancer that begins in the rectum is often called rectal cancer, but sometimes the term colorectal cancer is used for a cancer that begins in either place. This year about 132,700 people in the U.S. will be diagnosed with cancer of the colon or rectum. However, nearly 1.1 million remain alive today after having been diagnosed with colorectal cancer.

The colon and rectum are parts of the large intestine. In the colon, which accounts for most of the length of the large intestine, water and nutrients are extracted from partly-digested food before the food is turned into waste. The waste then enters the rectum before being pushed out of the body, leaving via the short anal canal and the anus (cancers also develop in the anus and anal canal, but they aren't classified as colorectal cancers). Most colon cancers and rectal cancers are adenocarcinomas, tumors that begin in gland-like cells lining the colon or rectum. Other types of cancerous tissues account for only 2% to 5% of colorectal cancers.

Colorectal cancer (and other tumors) can spread (metastasize) from the place where it started (the primary tumor) in 3 ways. First, it can invade the normal tissue surrounding it. Second, cancer cells can enter the lymph system and travel through lymph vessels to distant parts of the body. Third, the cancer cells can get into the bloodstream and go to other places in the body. In these distant places, the colon/rectal cancer cells cause secondary tumors to grow. The main sites to which colorectal cancer spreads are the liver, lungs and peritoneum. To find out whether the cancer has entered the lymph system, a surgeon removes all or part of a node near the primary tumor and a pathologist examines it to see if cancer cells are present. Several kinds of imaging also can be performed to determine if the cancer has spread. These include chest x-rays, MRI, CT scans and PET scans.

The FDA has approved several targeted therapies for treatment of patients with metastatic colorectal cancer. These include bevacizumab (Avastin), cetuximab (Erbitux), panitumumab (Vectibix) and ziv-afibercept (Zaltrap).

Despite significant improvements in the treatment of colorectal cancers, novel therapies and treatment strategies are needed.

Source: National Cancer Institute, 2015
The prognosis of patients with colon cancer is clearly related to the degree of tumor penetration through the bowel wall, the presence or absence of nodal involvement, and the presence or absence of distant metastases. These three characteristics form the basis for all staging systems developed for this disease. Bowel obstruction and bowel perforation are indicators of poor prognosis. Elevated pretreatment serum levels of carcinoembryonic antigen (CEA) have a negative prognostic significance. The American Joint Committee on Cancer and a National Cancer Institute-sponsored panel recommended that at least 12 lymph nodes be examined in patients with colon and rectal cancer to confirm the absence of nodal involvement by tumor. This recommendation takes into consideration that the number of lymph nodes examined is a reflection of the aggressiveness of lymphovascular mesenteric dissection at the time of surgical resection and the pathologic identification of nodes in the specimen. Retrospective studies demonstrated that the number of lymph nodes examined in colon and rectal surgery may be associated with patient outcome.

Many other prognostic markers have been evaluated retrospectively for patients with colon cancer, though most have not been prospectively validated (including allelic loss of chromosome 18q or thymidylate synthase expression). Microsatellite instability, also associated with hereditary nonpolyposis colon cancer (HNPCC), has been associated with improved survival (independent of tumor stage) in a population-based series of 607 patients younger than 50 years of age with colorectal cancer. Treatment decisions generally depend on factors such as physician/patient preferences and the stage of the disease, rather than the age of the patient. Racial differences in overall survival after adjuvant therapy have been observed (although not in disease-free survival), suggesting that comorbid conditions play a role in survival outcome in different patient populations.

Source: National Cancer Institute, 2012
Expand Collapse EGFR  - General Description
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The EGFR gene encodes for a cell-surface protein known as the epidermal growth factor receptor, which is found in many normal epithelial tissues such as the skin and hair follicles. When members of the epidermal growth factor family attach to EGFR, they activate several different cell signaling pathways that control various cell functions, including cell growth.

Mutations in EGFR can lead to unregulated activation of the protein. These types of activating mutations are often found in NSCLC (non-small cell lung cancer), glioblastoma and head and neck squamous cell carcinoma. Sometimes, excess EGFR protein is produced due to the presence of too many copies of the EGFR gene, leading to excessive cell division and growth in the presence of epidermal growth factor. Among the human cancers in which EGFR overabundance is present are cancers of the head and neck (squamous cell), colon, rectum, lung (NSCLC), central nervous system (glioblastoma), pancreas and breast (HER2-positive metastatic). Blocking EGFR in tumors may keep cancer cells from growing. The FDA has approved several therapies that target EGFR in one or more cancers.

Tumor mutation profiling performed clinically at the MGH Cancer Center has indicated that EGFR mutations occur primarily in lung cancer (~15%), but also in a minor subset of gastric (2%), brain (1%) and pancreatic (1%) cancers.

Source: Genetics Home Reference
The epidermal growth factor receptor (EGFR) gene encodes for a cell-surface protein that belongs to the ERBB family of receptor tyrosine kinases. Four members of the ERBB family have been identified: EGFR (ERBB1, HER1), ERBB2 (HER2), ERBB3 (HER3) and ERBB4 (HER4). Binding of a ligand induces ERBB receptor homo-/hetero-dimerization and triggers a signaling cascade that drives many cellular responses. These include the activation of PI3K-AKT/mTOR and MAP kinase/ERK pathways, which promote cell survival and proliferation. EGFR mutations have been most frequently associated with non-small cell lung cancer, but have also been described in other malignancies including gliomas, head and neck, prostate and ovarian tumors.

Tumor mutation profiling performed clinically at the MGH Cancer Center has indicated that EGFR mutations occur primarily in lung cancer (~15%), but also in a minor subset of gastric (2%), brain (1%) and pancreatic (1%) cancers.

Source: Genetics Home Reference
PubMed ID's
15864276, 15118073, 15118125, 15329413, 18772890, 15837736, 16720329, 21057220
Expand Collapse G719S (c.2155G>A)  in EGFR
The EGFR G719S mutation arises from the nucleotide change c.2155G>A in exon 18, resulting in an amino acid substitution of the glycine (G) at position 719 by a serine (S).
The EGFR G719S mutation arises from the nucleotide change c.2155G>A in exon 18, resulting in an amino acid substitution of the glycine (G) at position 719 by a serine (S).

The frequency of EGFR mutations in colorectal cancer is extremely low and the prognostic significance of these mutations has yet to be determined.

The therapeutic implications of EGFR mutations in colorectal cancer have not been determined. Therefore, it is unknown whether any particular EGFR gene mutation may confer sensitivity or resistance to EGFR small molecule inhibitors (such as erlotinib and gefitinib), as has been clearly demonstrated in non-small cell lung cancer.

The frequency of EGFR mutations in colorectal cancer is extremely low and the prognostic significance of these mutations has yet to be determined.

The therapeutic implications of EGFR mutations in colorectal cancer have not been determined. Therefore, it is unknown whether any particular EGFR gene mutation may confer sensitivity or resistance to EGFR small molecule inhibitors (such as erlotinib and gefitinib), as has been clearly demonstrated in non-small cell lung cancer.

PubMed ID's
15118125, 15118073, 15863375, 16166444, 15746034, 20184776, 20184776, 15625347, 16012179
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Your Matched Clinical Trials

Trial Matches: (D) - Disease, (G) - Gene, (M) - Mutation
Trial Status: Showing Results: 1-10 of 25 Per Page:
123Next »
Protocol # Title Location Status Match
NCT01953926 An Open-label, Phase 2 Study of Neratinib in Patients With Solid Tumors With Somatic Human Epidermal Growth Factor Receptor (EGFR, HER2, HER3) Mutations or EGFR Gene Amplification An Open-label, Phase 2 Study of Neratinib in Patients With Solid Tumors With Somatic Human Epidermal Growth Factor Receptor (EGFR, HER2, HER3) Mutations or EGFR Gene Amplification MGH Open DGM
NCT02365662 A Study Evaluating Safety and Pharmacokinetics of ABBV-221 in Subjects With Advanced Solid Tumor Types Likely to Exhibit Elevated Levels of Epidermal Growth Factor Receptor A Study Evaluating Safety and Pharmacokinetics of ABBV-221 in Subjects With Advanced Solid Tumor Types Likely to Exhibit Elevated Levels of Epidermal Growth Factor Receptor MGH Open DG
NCT01633970 A Study of Atezolizumab Administered in Combination With Bevacizumab and/or With Chemotherapy in Participants With Locally Advanced or Metastatic Solid Tumors A Study of Atezolizumab Administered in Combination With Bevacizumab and/or With Chemotherapy in Participants With Locally Advanced or Metastatic Solid Tumors MGH Open DG
NCT02279433 A First-in-human Study to Evaluate the Safety, Tolerability and Pharmacokinetics of DS-6051b A First-in-human Study to Evaluate the Safety, Tolerability and Pharmacokinetics of DS-6051b MGH Open D
NCT02099058 A Phase 1/1b Study With ABBV-399, an Antibody Drug Conjugate, in Subjects With Advanced Solid Cancer Tumors A Phase 1/1b Study With ABBV-399, an Antibody Drug Conjugate, in Subjects With Advanced Solid Cancer Tumors 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
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
NCT02467361 A Study of BBI608 Administered in Combination With Immune Checkpoint Inhibitors in Adult Patients With Advanced Cancers A Study of BBI608 Administered in Combination With Immune Checkpoint Inhibitors in Adult Patients With Advanced Cancers MGH Open D
NCT02082210 A Study of LY2875358 in Combination With Ramucirumab (LY3009806) in Participants With Advanced Cancer A Study of LY2875358 in Combination With Ramucirumab (LY3009806) in Participants With Advanced Cancer MGH Open D
Trial Status: Showing Results: 1-10 of 25 Per Page:
123Next »
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