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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 AKT1  - General Description
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AKT1 is a gene that provides the code for making a protein that plays a pivotal role in important signaling pathways. These pathways help control how cells grow and divide (proliferate), survive, become able to perform specific tasks (differentiate), and eventually destroy themselves when they're damaged or no longer needed (apoptosis). AKT1 seems especially important for the normal development and function of the nervous system.

When AKT1 is mutated, it may act as an oncogene causing normal cells to become cancerous. Mutations of the AKT1 gene sometimes are found in breast, ovarian and colorectal cancers. These mutations allow cells to grow without control, resulting in the formation of cancerous tumors. Somatic mutations in AKT are found in some cancers. Somatic mutations are those that instead of coming from a parent and being present in every cell (hereditary), somatic mutations are acquired during the course of a person's life and are found only in cells that become cancerous.

Tumor mutation profiling performed clinically at the MGH Cancer Center has confirmed that AKT1 gene mutations are rare in cancer. The highest incidence of AKT1 mutations were found in a small subset of brain meningiomas (8-13%), endometrial cancer (5%), breast cancer (2%), ovarian cancer (1%) or cancers of the head and neck (1%).

Source: Genetics Home Reference
The AKT family of serine-threonine protein kinases serve as a central signaling cascade downstream of PI3K, regulating a number of processes involved in cell proliferation, survival, metabolism and angiogenesis. The activation of AKT is normally dependent on recruitment to the plasma cell membrane by PI3K activation, where AKT is phosphorylated and activated by PDK1 and mTORC2. The three AKT isoforms AKT1, AKT2 and AKT3 are known to regulate distinct physiological functions. AKT1 induces protein synthesis pathways (e.g. mTOR) and inhibits apoptotic pathways (e.g. BAD). AKT1 E17K is the major somatic gene mutation identified in the AKT family in cancers, leading to PI3K-independent membrane recruitment and deregulation of the isoform AKT1's normal specificity.

Tumor mutation profiling performed clinically at the MGH Cancer Center has confirmed that AKT1 gene mutations are rare in cancers. The highest incidence of AKT1 mutations have been found in a subset of brain meningiomas (8-13%), endometrial cancer (5%), breast cancer (2%), ovarian cancer (1%) or cancers of the head and neck (1%).

Source: Genetics Home Reference
PubMed ID's
17611497, 19372382, 23334667
Expand Collapse E17K (c.49G>A)  in AKT1
The AKT1 E17K mutation arises from a single nucleotide change (c.49G>A) and results in an amino acid substitution of the glutamic acid (E) at position 17 by a lysine (K).
The AKT1 E17K mutation arises from a single nucleotide change (c.49G>A) and results in an amino acid substitution of the glutamic acid (E) at position 17 by a lysine (K).

AKT1 mutations occur in approximately 1% of colorectal cancers and are usually found in tumors that do not carry PIK3CA mutations and that have intact PTEN function.

A single phase II clinical trial that evaluated the treatment of advanced colorectal cancer patients with perifosine (an AKT and PI3K inhibitor), in combination with chemotherapy, showed improved patient outcomes. However, the role of AKT1 mutations (or other PI3K pathway abnormalities) for selecting anti-cancer treatment is unknown at this time. A number of new selective and potent AKT small molecule inhibitors have just entered early phase clinical trials. Future correlative and genotype-directed studies will therefore be required to determine whether the AKT1 E17K mutation may be associated with increased sensitivity to AKT inhibitors.

AKT1 mutations occur in approximately 1% of colorectal cancers and are usually found in tumors that do not carry PIK3CA mutations and that have intact PTEN function.

A single phase II clinical trial that evaluated the treatment of advanced colorectal cancer patients with perifosine (an AKT and PI3K inhibitor), in combination with chemotherapy, showed improved patient outcomes. However, the role of AKT1 mutations (or other PI3K pathway abnormalities) for selecting anti-cancer treatment is unknown at this time. A number of new selective and potent AKT small molecule inhibitors have just entered early phase clinical trials. Future correlative and genotype-directed studies will therefore be required to determine whether the AKT1 E17K mutation may be associated with increased sensitivity to AKT inhibitors.

PubMed ID's
18272025, 17458693, 17278891, 17058289, 16760642, 16528479, 16138006, 16034524, 15569974, 21969495, 17611497
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Your Matched Clinical Trials

Trial Matches: (D) - Disease, (G) - Gene, (M) - Mutation
Trial Status: Showing Results: 1-10 of 27 Per Page:
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Protocol # Title Location Status Match
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
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 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
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 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
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
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
NCT02060188 A Study of Nivolumab and Nivolumab Plus Ipilimumab in Recurrent and Metastatic Colon Cancer (CheckMate 142) A Study of Nivolumab and Nivolumab Plus Ipilimumab in Recurrent and Metastatic Colon Cancer (CheckMate 142) MGH Open D
Trial Status: Showing Results: 1-10 of 27 Per Page:
123Next »
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