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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 PTEN  - General Description
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PTEN is a gene that provides the code for making a protein called phosphatase and tensin homolog (PTEN). Found in almost all tissues in the body, this protein acts as a tumor suppressor. That is, it keeps cells from growing and dividing too fast or in an uncontrolled way. The PTEN protein is part of a signaling pathway that tells cells to stop dividing and triggers their self-destruction (apoptosis). It also may help control how cells move (migration), stick to other cells (adhesion) and protect their genetic information.

Somatic mutations in PTEN are among the most common genetic changes found in human cancers. 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. PTEN may be the most frequently mutated gene in prostate cancer and endometrial cancer. These mutations usually result in a defective protein that has lost its ability to be a tumor suppressor. Such mutations also are found in certain brain tumors (glioblastomas and astrocytomas) and melanoma of the skin. Loss of PTEN expression is also a common way by which PTEN activity can be reduced and the PI3K pathway can be activated.

Several related conditions caused by inherited mutations in PTEN are grouped together as PTEN hamartoma tumor syndrome. One of these conditions is Cowden syndrome, which is characterized by the growth of many hamartomas and an increased risk of developing breast, thyroid or endometrial cancer. Mutations that cause Cowden syndrome lead to production of a defective PTEN protein that cannot stop cell division or trigger apoptosis, which contributes to the development of hamartomas and cancerous tumors.

Source: Genetics Home Reference
The PTEN gene encodes a lipid phosphatase that antagonizes oncogenic PI3K/AKT signaling via dephosphorylation of phosphatidylinositol (3,4,5)-trisphosphate (PIP3) at the cell membrane. Cancer-associated genomic alterations in PTEN result in PTEN inactivation and thus increased activity of the PI3K/AKT pathway. Somatic mutations of PTEN occur in multiple malignancies, including gliomas, melanoma, prostate, endometrial, breast, ovarian, renal and lung cancers. Germline PTEN mutations are associated with inherited hamartoma syndromes, including Cowden syndrome. Loss of PTEN expression is also a common way by which PTEN activity can be reduced and the PI3K pathway can be activated.

Source: Genetics Home Reference
Expand Collapse PTEN  in Colorectal Cancer
An association between PTEN abnormalities and resistance to anti-EGFR treatments (such as cetuximab or panitumumab) has been indicated but not clearly established in colorectal cancer.

Recent data suggest that the P110 beta catalytic subunit of PI3K drives the growth of tumors when PTEN function is lost, but evidence in colorectal cancer is lacking. The role of PTEN mutations in predicting response to PI3K (including selective P110 beta), AKT and mTOR inhibitors is currently being explored in multiple clinical trials.

The prognostic impact of PTEN mutations in colorectal cancer has not been extensively studied, but most studies suggest that PTEN loss is a marker of poor clinical outcome.

An association between PTEN abnormalities and resistance to anti-EGFR treatments (such as cetuximab or panitumumab) has been indicated but not clearly established in colorectal cancer.

Recent data suggest that the P110 beta catalytic subunit of PI3K drives the growth of tumors when PTEN function is lost, but evidence in colorectal cancer is lacking. The role of PTEN mutations in predicting response to PI3K (including selective P110 beta), AKT and mTOR inhibitors is currently being explored in multiple clinical trials.

The prognostic impact of PTEN mutations in colorectal cancer has not been extensively studied, but most studies suggest that PTEN loss is a marker of poor clinical outcome.

PubMed ID's
20102402, 19724853, 19036165, 18755892, 18669866, 19117997, 18606717, 19401449
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 Results: 1-10 of 27 Per Page:
123Next »
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
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
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
Trial Status: Showing Results: 1-10 of 27 Per Page:
123Next »
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