Sunday, March 11, 2012
........................................
http://www.nature.com/nrclinonc/journal/v3/n11/full/ncponc0636.html
mesenchymal (BEZ235, abl/src inhibitor)
proliferative(anthracycline, docetaxel, paclitaxel, cisplatin)
Search GEO for "Anthracycline"
GSE25055, GSE25066
http://en.wikipedia.org/wiki/Taxane
http://en.wikipedia.org/wiki/Anthracycline
http://www.medscape.com/viewarticle/547360_3
Mutations in p53 and BRCA1(both somatic and germ-line) are more common in basal-like breast cancers than in other subtypes, and these cancers are also more sensitive to anthracyclines. Laboratory studies suggest that normal p53 function is necessary for initiation of cell death in BRCA1 wild-type cell lines, whereas cell death is p53-independent in BRCA1-mutated cell lines.[57] Based on these in vitro observations, one could hypothesize that p53 mutations predict resistance in luminal cancers, whereas such an association might not be present in basal-like cancers. Indeed, several reports showed that mutated p53 correlated with resistance to anthracyclines;[58] however, another study suggested that mutated p53 correlated closely with the efficacy of anthracycline-based chemotherapy.[59] One possible explanation for the discrepant results is that the first study mostly included luminal cancers (in which p53 correlates with resistance) and the second study inadvertently included more basal-like cancers and, therefore, p53 mutation status simply served as a surrogate to identify the generally chemotherapy-sensitive molecular subtype. Remarkably, comparison of the patient populations of the two studies showed substantial differences-72% of the patients included in the Geisler et al. study[58] had low-grade or intermediate-grade tumors, whereas in the Bertheau et al. study[59] most patients were ER-negative and high-grade. These observations suggest that testing single bio-markers in predefined molecular subsets of breast cancer or applying supervised outcome prediction methods to specific subsets could identify molecular-class-specific predictive signatures.
metabolic(5-fu, methotrexate)
mesenchymal (BEZ235, abl/src inhibitor)
proliferative(anthracycline, docetaxel, paclitaxel, cisplatin)
Search GEO for "Anthracycline"
GSE25055, GSE25066
http://en.wikipedia.org/wiki/Taxane
http://en.wikipedia.org/wiki/Anthracycline
http://www.medscape.com/viewarticle/547360_3
Mutations in p53 and BRCA1(both somatic and germ-line) are more common in basal-like breast cancers than in other subtypes, and these cancers are also more sensitive to anthracyclines. Laboratory studies suggest that normal p53 function is necessary for initiation of cell death in BRCA1 wild-type cell lines, whereas cell death is p53-independent in BRCA1-mutated cell lines.[57] Based on these in vitro observations, one could hypothesize that p53 mutations predict resistance in luminal cancers, whereas such an association might not be present in basal-like cancers. Indeed, several reports showed that mutated p53 correlated with resistance to anthracyclines;[58] however, another study suggested that mutated p53 correlated closely with the efficacy of anthracycline-based chemotherapy.[59] One possible explanation for the discrepant results is that the first study mostly included luminal cancers (in which p53 correlates with resistance) and the second study inadvertently included more basal-like cancers and, therefore, p53 mutation status simply served as a surrogate to identify the generally chemotherapy-sensitive molecular subtype. Remarkably, comparison of the patient populations of the two studies showed substantial differences-72% of the patients included in the Geisler et al. study[58] had low-grade or intermediate-grade tumors, whereas in the Bertheau et al. study[59] most patients were ER-negative and high-grade. These observations suggest that testing single bio-markers in predefined molecular subsets of breast cancer or applying supervised outcome prediction methods to specific subsets could identify molecular-class-specific predictive signatures.
metabolic(5-fu, methotrexate)
Saturday, March 10, 2012
Tamoxifen
D subtype == LumA response to Tamoxifen
Definition of Clinically Distinct Molecular Subtypes in
Estrogen Receptor–Positive Breast Carcinomas Through
Genomic Grade
http://www.biomedcentral.com/1755-8794/2/37
Sherene Loi, from the Peter MacCallum Cancer Centre, Melbourne, worked with a team of Australian and Belgian researchers to investigate the differences between those estrogen receptor positive (ER+) cancers that respond well to tamoxifen (luminal-A) and those that do not (luminal-B). She said, “This is the first study specifically investigating the biology of the luminal-B, ER+ breast cancer subtype. We propose that activation of GF signaling contributes to this highly proliferative, relatively tamoxifen-insensitive, phenotype and that this exists independently of HER2 overexpression. Targeting this pathway and its upstream mediators could prove to be a useful therapeutic strategy
http://www.sciencedaily.com/releases/2009/06/090623215852.htm
and
http://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE2990
Definition of Clinically Distinct Molecular Subtypes in
Estrogen Receptor–Positive Breast Carcinomas Through
Genomic Grade
http://www.biomedcentral.com/1755-8794/2/37
Gene expression profiling identifies activated growth factor signaling in poor prognosis (Luminal-B) estrogen receptor positive breast cancer
http://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE6532Sherene Loi, from the Peter MacCallum Cancer Centre, Melbourne, worked with a team of Australian and Belgian researchers to investigate the differences between those estrogen receptor positive (ER+) cancers that respond well to tamoxifen (luminal-A) and those that do not (luminal-B). She said, “This is the first study specifically investigating the biology of the luminal-B, ER+ breast cancer subtype. We propose that activation of GF signaling contributes to this highly proliferative, relatively tamoxifen-insensitive, phenotype and that this exists independently of HER2 overexpression. Targeting this pathway and its upstream mediators could prove to be a useful therapeutic strategy
http://www.sciencedaily.com/releases/2009/06/090623215852.htm
and
http://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE2990
Friday, March 9, 2012
Grading
The neoplastic grading is a measure of cell anaplasia (lack of differentiation) in the sampled tumor and is based on the resemblance of the tumor to the tissue of origin.
Anaplasia refers to a reversion of differentiation in cells and is characteristic of malignant neoplasms (tumors). Sometimes, the term also includes an increased capacity for multiplication.[1] Lack of differentiation is considered a hallmark of aggressive malignancies. The term anaplasia literally means "to form backward". It implies dedifferentiation, or loss of structural and functional differentiation of normal cells. It is now known, however, that at least some cancers arise from stem cells in tissues; in these tumors failure of differentiation, rather than dedifferentiation of specialized cells, account for undifferentiated tumors.
Anaplasia refers to a reversion of differentiation in cells and is characteristic of malignant neoplasms (tumors). Sometimes, the term also includes an increased capacity for multiplication.[1] Lack of differentiation is considered a hallmark of aggressive malignancies. The term anaplasia literally means "to form backward". It implies dedifferentiation, or loss of structural and functional differentiation of normal cells. It is now known, however, that at least some cancers arise from stem cells in tissues; in these tumors failure of differentiation, rather than dedifferentiation of specialized cells, account for undifferentiated tumors.
Thursday, March 8, 2012
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