Bladder Cancer, PTEN, Loss of Function

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Expand Collapse Bladder Cancer  - General Description This year about 74,000 people in the U.S. (76% of them men and half will be over the age of 73 years old) will be told by a doctor that they have cancer of the urinary bladder. With significant improvements in the treatment of this malignancy, about 550,000 of them remain alive today.

Bladder cancer begins in different types of cells found in the inner lining of the bladder, the flexible muscular organ that stores urine. Transitional cells, which stretch or shrink as the bladder fills or empties, account for 90% of bladder cancers in the United States. Less commonly (in 6-8% of U.S. bladder cancers), the cancer begins in squamous cells that may form in response to irritation or infection that has lasted a long time. Adenocarcinoma begins in cells that make mucous and accounts for only about 2% of U.S. bladder cancers. Adenocarcinoma of the bladder is also believed to be a result of long-lasting irritation or inflammation.

If the cancer stays in the lining of the bladder, it is called superficial bladder cancer. Sometimes, though, transitional cell cancer spreads through the lining and breaks into the muscular wall beneath it or spreads to nearby organs and lymph nodes. In this case it is known as invasive bladder cancer.

Bladder 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, bladder 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 blood stream and go to other places in the body. In these distant places, the bladder cancer cells cause secondary (metastatic) tumors to grow, in the bones, for example. To find out whether the cancer has entered the lymph system, a surgeon removes all or part of a lymph node and a pathologist inspects it under a microscope. Several kinds of imaging can also be performed to determine if bladder cancer has spread. These include CT scans, MRI, chest x-rays and bone scans.

Source: National Cancer Institute, 2012
This year about 74,000 people in the U.S. (76% of them men and half will be over the age of 73 years old) will be told by a doctor that they have cancer of the urinary bladder. With significant improvements in the treatment of this malignancy, about 550,000 of them remain alive today.

Bladder cancer begins in different types of cells found in the inner lining of the bladder, the flexible muscular organ that stores urine. Transitional cells, which stretch or shrink as the bladder fills or empties, account for 90% of bladder cancers in the United States. Less commonly (in 6-8% of U.S. bladder cancers), the cancer begins in squamous cells that may form in response to irritation or infection that has lasted a long time. Adenocarcinoma begins in cells that make mucous and accounts for only about 2% of U.S. bladder cancers. Adenocarcinoma of the bladder is also believed to be a result of long-lasting irritation or inflammation.

If the cancer stays in the lining of the bladder, it is called superficial bladder cancer. Sometimes, though, transitional cell cancer spreads through the lining and breaks into the muscular wall beneath it or spreads to nearby organs and lymph nodes. In this case it is known as invasive bladder cancer.

Bladder 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, bladder 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 blood stream and go to other places in the body. In these distant places, the bladder cancer cells cause secondary (metastatic) tumors to grow, in the bones, for example. To find out whether the cancer has entered the lymph system, a surgeon removes all or part of a lymph node and a pathologist inspects it under a microscope. Several kinds of imaging can also be performed to determine if bladder cancer has spread. These include CT scans, MRI, chest x-rays and bone scans.

Source: National Cancer Institute, 2012
This year about 74,000 people in the U.S. (76% of them men and half will be over the age of 73 years old) will be told by a doctor that they have cancer of the urinary bladder. With significant improvements in the treatment of this malignancy, about 550,000 of them remain alive today.

Bladder cancer begins in different types of cells found in the inner lining of the bladder, the flexible muscular organ that stores urine. Transitional cells, which stretch or shrink as the bladder fills or empties, account for 90% of bladder cancers in the United States. Less commonly (in 6-8% of U.S. bladder cancers), the cancer begins in squamous cells that may form in response to irritation or infection that has lasted a long time. Adenocarcinoma begins in cells that make mucous and accounts for only about 2% of U.S. bladder cancers. Adenocarcinoma of the bladder is also believed to be a result of long-lasting irritation or inflammation.

If the cancer stays in the lining of the bladder, it is called superficial bladder cancer. Sometimes, though, transitional cell cancer spreads through the lining and breaks into the muscular wall beneath it or spreads to nearby organs and lymph nodes. In this case it is known as invasive bladder cancer.

Bladder 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, bladder 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 blood stream and go to other places in the body. In these distant places, the bladder cancer cells cause secondary (metastatic) tumors to grow, in the bones, for example. To find out whether the cancer has entered the lymph system, a surgeon removes all or part of a lymph node and a pathologist inspects it under a microscope. Several kinds of imaging can also be performed to determine if bladder cancer has spread. These include CT scans, MRI, chest x-rays and bone scans.

Source: National Cancer Institute, 2012
This year about 74,000 people in the U.S. (76% of them men and half will be over the age of 73 years old) will be told by a doctor that they have cancer of the urinary bladder. With significant improvements in the treatment of this malignancy, about 550,000 of them remain alive today.

Bladder cancer begins in different types of cells found in the inner lining of the bladder, the flexible muscular organ that stores urine. Transitional cells, which stretch or shrink as the bladder fills or empties, account for 90% of bladder cancers in the United States. Less commonly (in 6-8% of U.S. bladder cancers), the cancer begins in squamous cells that may form in response to irritation or infection that has lasted a long time. Adenocarcinoma begins in cells that make mucous and accounts for only about 2% of U.S. bladder cancers. Adenocarcinoma of the bladder is also believed to be a result of long-lasting irritation or inflammation.

If the cancer stays in the lining of the bladder, it is called superficial bladder cancer. Sometimes, though, transitional cell cancer spreads through the lining and breaks into the muscular wall beneath it or spreads to nearby organs and lymph nodes. In this case it is known as invasive bladder cancer.

Bladder 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, bladder 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 blood stream and go to other places in the body. In these distant places, the bladder cancer cells cause secondary (metastatic) tumors to grow, in the bones, for example. To find out whether the cancer has entered the lymph system, a surgeon removes all or part of a lymph node and a pathologist inspects it under a microscope. Several kinds of imaging can also be performed to determine if bladder cancer has spread. These include CT scans, MRI, chest x-rays and bone scans.

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 Loss of Function  in PTEN
The loss of function of a gene such as PTEN can occur through several genetic alteration mechanisms. Sometimes there is a loss of one copy of the gene, resulting in a loss of production of the protein within tumor cells. In other tumors, deletions of portions of the gene have been found that result in an incomplete protein, and without the missing portions of the protein PTEN cannot perform its normal function in the cell. In another subset of cancers, mutations in the sequence of the PTEN gene have been found, which result in an altered amino acid sequence in the protein. All three of these genetic alterations have been found in different tumors, and each results in a PTEN protein that is either missing or altered such that does not perform its normal growth suppression role in cancer cells.
The loss of function of a gene such as PTEN can occur through several genetic alteration mechanisms. Sometimes there is a loss of one copy of the gene, resulting in a loss of production of the protein within tumor cells. In other tumors, deletions of portions of the gene have been found that result in an incomplete protein, and without the missing portions of the protein PTEN cannot perform its normal function in the cell. In another subset of cancers, mutations in the sequence of the PTEN gene have been found, which result in an altered amino acid sequence in the protein. All three of these genetic alterations have been found in different tumors, and each results in a PTEN protein that is either missing or altered such that does not perform its normal growth suppression role in cancer cells.

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Your Matched Clinical Trials

Trial Matches: (D) - Disease, (G) - Gene, (M) - Mutation
Trial Status: Showing Results: 1-10 of 19 Per Page:
12Next »
Protocol # Title Location Status Match
NCT02052778 A Dose Finding Study Followed by a Safety and Efficacy Study in Patients With Advanced Solid Tumors or Multiple Myeloma With FGF/FGFR-Related Abnormalities A Dose Finding Study Followed by a Safety and Efficacy Study in Patients With Advanced Solid Tumors or Multiple Myeloma With FGF/FGFR-Related Abnormalities MGH Open D
NCT02897765 A Personalized Cancer Vaccine (NEO-PV-01) w/ Nivolumab for Patients With Melanoma, Lung Cancer or Bladder Cancer A Personalized Cancer Vaccine (NEO-PV-01) w/ Nivolumab for Patients With Melanoma, Lung Cancer or Bladder Cancer MGH Open D
NCT02450331 A Study of Atezolizumab Versus Observation as Adjuvant Therapy in Participants With High-Risk Muscle-Invasive Urothelial Carcinoma (UC) After Surgical Resection A Study of Atezolizumab Versus Observation as Adjuvant Therapy in Participants With High-Risk Muscle-Invasive Urothelial Carcinoma (UC) After Surgical Resection MGH Open D
NCT02603432 A Study Of Avelumab In Patients With Locally Advanced Or Metastatic Urothelial Cancer (JAVELIN Bladder 100) A Study Of Avelumab In Patients With Locally Advanced Or Metastatic Urothelial Cancer (JAVELIN Bladder 100) MGH Open D
NCT02323191 A Study of Emactuzumab and Atezolimumab Administered in Combination in Participants With Advanced Solid Tumors A Study of Emactuzumab and Atezolimumab Administered in Combination in Participants With Advanced Solid Tumors MGH Open D
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 D
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 D
NCT02989064 MAGE-A10ᶜ⁷⁹⁶T for Urothelial Cancer, Melanoma or Head and Neck Cancers MAGE-A10ᶜ⁷⁹⁶T for Urothelial Cancer, Melanoma or Head and Neck Cancers MGH Open D
NCT02465060 NCI-MATCH: Targeted Therapy Directed by Genetic Testing in Treating Patients With Advanced Refractory Solid Tumors, Lymphomas, or Multiple Myeloma NCI-MATCH: Targeted Therapy Directed by Genetic Testing in Treating Patients With Advanced Refractory Solid Tumors, Lymphomas, or Multiple Myeloma MGH Open D
NCT02655822 Phase 1/1b Study to Evaluate the Safety and Tolerability of CPI-444 Alone and in Combination With Atezolizumab in Advanced Cancers Phase 1/1b Study to Evaluate the Safety and Tolerability of CPI-444 Alone and in Combination With Atezolizumab in Advanced Cancers MGH Open D
Trial Status: Showing Results: 1-10 of 19 Per Page:
12Next »
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