Breast Cancer, PTEN, Loss of Function

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Expand Collapse Breast Cancer  - General Description Breast cancer is the most common non-cutaneous cancer among women in the United States. This year about 252,710 women in the U.S. will be told by a doctor that they have breast cancer. Half of these people will be at least 62 years old. However, an estimated 3,327,552 women are living with female breast cancer in the United States following treatment.

Germline mutations in either the BRCA1 or BRCA2 gene confer an increased risk of breast and/or ovarian cancer. In addition, mutation carriers may be at increased risk of other primary cancers. Genetic testing is available to detect mutations in members of high-risk families. Such individuals should first be referred for counseling. Breast cancer is commonly treated by various combinations of surgery, radiation therapy, chemotherapy and hormone therapy.

Over the past years, significant major strides in understanding the biology of breast cancer have translated into actionable targeted therapies. For metastatic hormone receptor positive breast cancer, FDA approved therapies include tamoxifen, a selective estrogen modulator, aromatase inhibitors including exemestane, letrozole, and anastrozole, fulvestrant, a selective estrogen receptor blocker, and more recently everoliumus, a mTOR inhibitor, in combination with exemestane.

Despite significant improvements in the treatment of breast tumors, novel therapies and treatment strategies are needed. There are a number of novel therapies in development tailored to specific somatic mutations in the tumor.

Source: National Cancer Institute, 2017
Breast cancer is the most common non-cutaneous cancer among women in the United States. This year about 252,710 women in the U.S. will be told by a doctor that they have breast cancer. Half of these people will be at least 62 years old. However, an estimated 3,327,552 women are living with female breast cancer in the United States following treatment.

Germline mutations in either the BRCA1 or BRCA2 gene confer an increased risk of breast and/or ovarian cancer. In addition, mutation carriers may be at increased risk of other primary cancers. Genetic testing is available to detect mutations in members of high-risk families. Such individuals should first be referred for counseling. Breast cancer is commonly treated by various combinations of surgery, radiation therapy, chemotherapy and hormone therapy.

Over the past years, significant major strides in understanding the biology of breast cancer have translated into actionable targeted therapies. For metastatic hormone receptor positive breast cancer, FDA approved therapies include tamoxifen, a selective estrogen modulator, aromatase inhibitors including exemestane, letrozole, and anastrozole, fulvestrant, a selective estrogen receptor blocker, and more recently everoliumus, a mTOR inhibitor, in combination with exemestane.

Despite significant improvements in the treatment of breast tumors, novel therapies and treatment strategies are needed. There are a number of novel therapies in development tailored to specific somatic mutations in the tumor.

Source: National Cancer Institute, 2017
Breast cancer is the most common non-cutaneous cancer among women in the United States. This year about 252,710 women in the U.S. will be told by a doctor that they have breast cancer. Half of these people will be at least 62 years old. However, an estimated 3,327,552 women are living with female breast cancer in the United States following treatment.

Germline mutations in either the BRCA1 or BRCA2 gene confer an increased risk of breast and/or ovarian cancer. In addition, mutation carriers may be at increased risk of other primary cancers. Genetic testing is available to detect mutations in members of high-risk families. Such individuals should first be referred for counseling. Breast cancer is commonly treated by various combinations of surgery, radiation therapy, chemotherapy and hormone therapy.

Over the past years, significant major strides in understanding the biology of breast cancer have translated into actionable targeted therapies. For metastatic hormone receptor positive breast cancer, FDA approved therapies include tamoxifen, a selective estrogen modulator, aromatase inhibitors including exemestane, letrozole, and anastrozole, fulvestrant, a selective estrogen receptor blocker, and more recently everoliumus, a mTOR inhibitor, in combination with exemestane.

Despite significant improvements in the treatment of breast tumors, novel therapies and treatment strategies are needed. There are a number of novel therapies in development tailored to specific somatic mutations in the tumor.

Source: National Cancer Institute, 2017
Breast cancer is the most common non-cutaneous cancer among women in the United States. This year about 252,710 women in the U.S. will be told by a doctor that they have breast cancer. Half of these people will be at least 62 years old. However, an estimated 3,327,552 women are living with female breast cancer in the United States following treatment.

Germline mutations in either the BRCA1 or BRCA2 gene confer an increased risk of breast and/or ovarian cancer. In addition, mutation carriers may be at increased risk of other primary cancers. Genetic testing is available to detect mutations in members of high-risk families. Such individuals should first be referred for counseling. Breast cancer is commonly treated by various combinations of surgery, radiation therapy, chemotherapy and hormone therapy.

Over the past years, significant major strides in understanding the biology of breast cancer have translated into actionable targeted therapies. For metastatic hormone receptor positive breast cancer, FDA approved therapies include tamoxifen, a selective estrogen modulator, aromatase inhibitors including exemestane, letrozole, and anastrozole, fulvestrant, a selective estrogen receptor blocker, and more recently everoliumus, a mTOR inhibitor, in combination with exemestane.

Despite significant improvements in the treatment of breast tumors, novel therapies and treatment strategies are needed. There are a number of novel therapies in development tailored to specific somatic mutations in the tumor.

Source: National Cancer Institute, 2017
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 parts 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; and 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 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 parts 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; and 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 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 parts 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; and 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 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 parts 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; and 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 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 44 Per Page:
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Protocol # Title Location Status Match
NCT02684032 A Study To Assess The Tolerability And Clinical Activity Of Gedatolisib In Combination With Palbociclib/Letrozole Or Palbociclib/Fulvestrant In Women With Metastatic Breast Cancer A Study To Assess The Tolerability And Clinical Activity Of Gedatolisib In Combination With Palbociclib/Letrozole Or Palbociclib/Fulvestrant In Women With Metastatic Breast Cancer MGH Open DGM
NCT01971515 First-in-Human Dose Escalation Trial in Subjects With Advanced Malignancies First-in-Human Dose Escalation Trial in Subjects With Advanced Malignancies MGH Open DGM
NCT02732119 Study of Ribociclib With Everolimus + Exemestane in HR+ HER2- Locally Advanced/Metastatic Breast Cancer Post Progression on CDK 4/6 Inhibitor. Study of Ribociclib With Everolimus + Exemestane in HR+ HER2- Locally Advanced/Metastatic Breast Cancer Post Progression on CDK 4/6 Inhibitor. MGH Open DGM
NCT01296555 A Dose Escalation Study Evaluating the Safety and Tolerability of GDC-0032 in Participants With Locally Advanced or Metastatic Solid Tumors or Non-Hodgkin's Lymphoma (NHL) and in Combination With Endocrine Therapy in Locally Advanced or Metastatic Hormone Receptor-Positive Breast Cancer A Dose Escalation Study Evaluating the Safety and Tolerability of GDC-0032 in Participants With Locally Advanced or Metastatic Solid Tumors or Non-Hodgkin's Lymphoma (NHL) and in Combination With Endocrine Therapy in Locally Advanced or Metastatic Hormone Receptor-Positive Breast Cancer MGH Open D
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
NCT02580448 A Open-Label Study to Evaluate the Safety, Tolerability, Pharmacokinetics, Pharmacodynamics and Efficacy of VT-464 in Patients With Advanced Breast Cancer A Open-Label Study to Evaluate the Safety, Tolerability, Pharmacokinetics, Pharmacodynamics and Efficacy of VT-464 in Patients With Advanced Breast Cancer 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
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
NCT02338349 A Phase I, Multicenter, Open-Label, Two-Part, Dose-escalation Study of RAD1901 in Postmenopausal Women With Advanced Estrogen Receptor Positive and HER2-Negative Breast Cancer A Phase I, Multicenter, Open-Label, Two-Part, Dose-escalation Study of RAD1901 in Postmenopausal Women With Advanced Estrogen Receptor Positive and HER2-Negative Breast Cancer MGH Open D
NCT01525589 A Phase II Clinical Trial of PM01183 in BRCA 1/2-Associated or Unselected Metastatic Breast Cancer A Phase II Clinical Trial of PM01183 in BRCA 1/2-Associated or Unselected Metastatic Breast Cancer MGH Open D
Trial Status: Showing Results: 1-10 of 44 Per Page:
12345Next »
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