loading...| Preferred Name |
Breast Cancer |
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| Synonyms |
PMID: 22082486 PathwayType: signaling Description: One of the more aggressive types of breast cancer is basal breast cancer (BBC). Pathway is built manually using published studies. CellType: cancer cell Notes: Headnote: Breast cancer (BC) is the most commonly diagnosed cancer in women (excluding skin cancer) and the second leading cause of cancer death in women. Men may also develop BC, but this accounts for less than 1% of all BCs. One of the major molecular subtypes of BC is basal breast cancer (BBC). Signaling description: BBC has cells with features similar to those of the outer (basal) cells lining the mammary ducts. Most BBCs are triple-negative breast cancers (TNBC). However, not all TNBCs are basal-like and not all BBCs are triple-negative. TNBC/BBC has estrogen receptor negative, progesterone receptor negative, human epidermal growth factor receptor 2 (HER2/neu) negative (ER-, PR-, ERBB2-) status. These are high-grade cancers that tend to grow quickly and have a poor prognosis. TNBC/BBC demonstrates overexpression of EGFR (epidermal growth factor receptor), VEGFRs (vascular endothelial growth factor receptors) including VEGFR1 (FLT1), VEGFR2 (KDR), and VEGFR3 (FLT4), LRP6 (low-density lipoprotein receptor-related protein 6), FZD7, KIT (c-kit receptor tyrosine kinase), TNFRSF10A (tumor necrosis factor receptor superfamily, member 10a), TGFBR1 (receptor 1 of transforming growth factor beta), and NOTCH1. In addition, there may be mutations in TP53, PTEN (antagonist of PIK3CA and suppressor of AKT1-mediated signaling pathways), and in DNA repair genes such as BRCA1, BRCA2, PALB2, RAD51, NBN, BRIP1, PARP1, and MLH1. This type of BC is more common among women with BRCA1 gene mutations. Hormone therapy is not effective against TNBC/BBC. This cancer is generally resistant to standard therapy, although chemotherapy may be helpful. MTOR inhibitors (Everolimus and Temsirolimus), inhibitor of SRC (Dasatinib), inhibitors of EGFR (Iressa (Gefitinib), Lapatinib and Cetuximab), inhibitors of KDR (Bevacizumab and Sutent (Sunitinib)), inhibitor of VEGFA (Bevacizumab), and inhibitors of KIT (Dasatinib and Imatinib) are used for the treatment of BC. The crucial pathogenic processes involved in TNBC/BBC are cell proliferation, block of apoptosis, cell invasion, chromatin remodeling, dysfunction of DNA repair, and loss of cell differentiation. Outcome effects: The overexpression of EGFR and VEGFRs causes constitutive activation of AKT1 and mitogen-activated protein kinase (MAPK) signaling cascades that result in block of apoptosis, loss of differentiation, proliferation, and migration of mammary epithelial cells. The overexpression of KIT and TGFBR1 triggers the activation of Janus kinases 1/2 (JAK1/2) and SMAD family members 2/3/4 (SMAD2/3/4) complexes, respectively which are involved in cell proliferation. The constitutive activation of NOTCH signaling leads to loss of differentiation and hyperplastic growth of mammary epithelial cells. The overexpression of FZD7 and LRP6 causes the constitutive activation of WNT/CTNNB1 signaling pathway resulting in loss of differentiation, redundant cell proliferation, and migration. The overexpression of TNFRSF10A over-activates NF-kB which participates in blocking apoptosis. Normally, BRCA1 and BRCA2 play a central role in DNA repair, response to DNA damage, prevention of chromosome breaks, and genomic stability. BRCA1 interacts with DNA mismatch repair protein complex MLH1/MSH2/MSH3/MSH6 and genes that participate in homologous recombination and double-strand break repair such as BRCA2, RAD51, BRIP1, PALB2, MRN complex (RAD50/MRE11A/NBN), and PARP1/2 via NBN. Mutations in these genes lead to block of DNA repair and dysfunction in response to DNA damage. Highlighted proteins: Proteins with increased expression or activity are highlighted in red. Mutated genes: Mutated genes are shown in white-out style. Link: https://mammal-profservices.pathwaystudio.com/app/sd?urn=urn:agi-pathway:uuid-d46f99a0-e29c-4dcf-8a31-4a8ec99b0a4b Tissue: epithelium CellType: mammary epithelial cell PMID: 19729680 PMID: 18779615 NodeType: Pathway PMID: 21076464 Organ_System: integumentary system Organ: breast Pathway_Author: M. Zharkova ORCID:0000-0001-8706-9411 Source: Diseases |
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urn:agi-pathway:uuid-d46f99a0-e29c-4dcf-8a31-4a8ec99b0a4b |
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| database_cross_reference |
PS:PathwayType PS:Description PS:Tissue PS:Pathway_Author PS:Link PS:CellType PS:Organ_System PS:PMID PS:NodeType PS:Notes PS:Organ PS:Source |
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| has_exact_synonym |
PMID: 22082486 PathwayType: signaling Description: One of the more aggressive types of breast cancer is basal breast cancer (BBC). Pathway is built manually using published studies. CellType: cancer cell Notes: Headnote: Breast cancer (BC) is the most commonly diagnosed cancer in women (excluding skin cancer) and the second leading cause of cancer death in women. Men may also develop BC, but this accounts for less than 1% of all BCs. One of the major molecular subtypes of BC is basal breast cancer (BBC). Signaling description: BBC has cells with features similar to those of the outer (basal) cells lining the mammary ducts. Most BBCs are triple-negative breast cancers (TNBC). However, not all TNBCs are basal-like and not all BBCs are triple-negative. TNBC/BBC has estrogen receptor negative, progesterone receptor negative, human epidermal growth factor receptor 2 (HER2/neu) negative (ER-, PR-, ERBB2-) status. These are high-grade cancers that tend to grow quickly and have a poor prognosis. TNBC/BBC demonstrates overexpression of EGFR (epidermal growth factor receptor), VEGFRs (vascular endothelial growth factor receptors) including VEGFR1 (FLT1), VEGFR2 (KDR), and VEGFR3 (FLT4), LRP6 (low-density lipoprotein receptor-related protein 6), FZD7, KIT (c-kit receptor tyrosine kinase), TNFRSF10A (tumor necrosis factor receptor superfamily, member 10a), TGFBR1 (receptor 1 of transforming growth factor beta), and NOTCH1. In addition, there may be mutations in TP53, PTEN (antagonist of PIK3CA and suppressor of AKT1-mediated signaling pathways), and in DNA repair genes such as BRCA1, BRCA2, PALB2, RAD51, NBN, BRIP1, PARP1, and MLH1. This type of BC is more common among women with BRCA1 gene mutations. Hormone therapy is not effective against TNBC/BBC. This cancer is generally resistant to standard therapy, although chemotherapy may be helpful. MTOR inhibitors (Everolimus and Temsirolimus), inhibitor of SRC (Dasatinib), inhibitors of EGFR (Iressa (Gefitinib), Lapatinib and Cetuximab), inhibitors of KDR (Bevacizumab and Sutent (Sunitinib)), inhibitor of VEGFA (Bevacizumab), and inhibitors of KIT (Dasatinib and Imatinib) are used for the treatment of BC. The crucial pathogenic processes involved in TNBC/BBC are cell proliferation, block of apoptosis, cell invasion, chromatin remodeling, dysfunction of DNA repair, and loss of cell differentiation. Outcome effects: The overexpression of EGFR and VEGFRs causes constitutive activation of AKT1 and mitogen-activated protein kinase (MAPK) signaling cascades that result in block of apoptosis, loss of differentiation, proliferation, and migration of mammary epithelial cells. The overexpression of KIT and TGFBR1 triggers the activation of Janus kinases 1/2 (JAK1/2) and SMAD family members 2/3/4 (SMAD2/3/4) complexes, respectively which are involved in cell proliferation. The constitutive activation of NOTCH signaling leads to loss of differentiation and hyperplastic growth of mammary epithelial cells. The overexpression of FZD7 and LRP6 causes the constitutive activation of WNT/CTNNB1 signaling pathway resulting in loss of differentiation, redundant cell proliferation, and migration. The overexpression of TNFRSF10A over-activates NF-kB which participates in blocking apoptosis. Normally, BRCA1 and BRCA2 play a central role in DNA repair, response to DNA damage, prevention of chromosome breaks, and genomic stability. BRCA1 interacts with DNA mismatch repair protein complex MLH1/MSH2/MSH3/MSH6 and genes that participate in homologous recombination and double-strand break repair such as BRCA2, RAD51, BRIP1, PALB2, MRN complex (RAD50/MRE11A/NBN), and PARP1/2 via NBN. Mutations in these genes lead to block of DNA repair and dysfunction in response to DNA damage. Highlighted proteins: Proteins with increased expression or activity are highlighted in red. Mutated genes: Mutated genes are shown in white-out style. Tissue: epithelium CellType: mammary epithelial cell PMID: 19729680 PMID: 18779615 NodeType: Pathway PMID: 21076464 Organ_System: integumentary system Organ: breast Pathway_Author: M. Zharkova ORCID:0000-0001-8706-9411 Source: Diseases |
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| id |
urn:agi-pathway:uuid-d46f99a0-e29c-4dcf-8a31-4a8ec99b0a4b |
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| label |
Breast Cancer |
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| notation |
uuid-d46f99a0-e29c-4dcf-8a31-4a8ec99b0a4b |
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| prefLabel |
Breast Cancer |
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| treeView |
urn:agi-folder:b urn:agi-folder:breast_cancer urn:agi-folder:epithelium urn:agi-folder:integumentary_system |
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| subClassOf |
urn:agi-folder:b urn:agi-folder:breast_cancer urn:agi-folder:epithelium urn:agi-folder:integumentary_system |