SnapShot: Breast Cancer - Stemcell Technologies › media › files › wallchart ›...
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TBL1XR1 Key signaling pathways in breast cancer based on somatic mutation data Frequency of breast cancer subtypes USH2A NF1 RAS SRC p53 TBX3 CDK4 Cyclin D1/3 MYC ER a NCOR1 RUNX1 CBFB GATA3 FOXA1 MYB pRB MDM2 AKT p27 Kip1 p16 Ink4A GSK-3 PTEN PI3K mTORC1 mTORC2 MAP3K1 MAP2K4 JNK STMN2 BRAF MEK1/2 ERK1/2 IGF-1R EGFR HER2 FGFR E-cadherin *Preinvasive stage **Estimated overall survival (OS) using HER2-targeted therapies Subtype *DCIS Luminal (non- HER2 + ) **HER2 + Stage 5 year OS (%) 10 year OS (%) 0 99 98 I 98 95 II 91 81 III 72 54 IV 33 17 I 98 95 II 92 86 III 85 75 IV 40 15 TNBC I 93 90 II 76 70 III 45 37 IV 15 11 Mutation frequencies (%) in all tumors, or just within luminal (including HER2 + ) and TNBC subtypes. Colors indicate tumor suppressors (blue), oncogenes (red), or mutant genes with unclear roles (purple), and lighter shading marks pathway components in which somatic mutations have not been identified. Top 21 most commonly mutated genes in breast cancer TP53 35 26 54 PIK3CA 34 44 8 GATA3 9 13 0 MAP3K1 8 11 0 MLL3 6 8 3 CDH1 6 8 2 USH2A 5 4 8 PTEN 3 3 3 RUNX1 3 4 0 MAP2K4 3 4 1 NCOR1 3 3 1 RB1 3 2 5 TBX3 2 3 1 PIK3R1 2 3 2 CTCF 2 2 1 NF1 2 2 1 SF3B1 2 2 0 AKT1 2 2 0 CBFB 1 2 1 FOXA1 1 1 1 CDKN1B 1 1 0 Gene All (%) Luminal TNBC 10 E X C I T I N G C A N C E R R E S E A R C H E X C I T I N G C A N C E R R E S E A R C H S I N C E 2 0 0 2 S I N C E 2 0 0 2 YEARS OF YEARS OF ER HER2 PI3K Pathway (PI3K, AKT, mTOR) Angiogenesis (VEGFR, PDGFR, KIT) Others (Target) a Raloxifene is used for breast cancer prevention, not treatment, b mTOR inhibitor, c dual PI3K/mTOR inhibitor, d AKT inhibitor, e also inhibits VEGFR. Tamoxifen Raloxifene a Fulvestrant Megestrol Toremifene Anastrozole Letrozole Exemestane Estradiol Pertuzumab Trastuzumab T-DM1 Lapatinib Neratinib MM-121 Afatinib Canertinib Dacomitinib IGF, IGF-1R MEDI-573 Figitumumab Linsitinib Ganitumab BMS-754807 Cixutumumab Dalotuzumab Everolimus b BYL719 AZD8055 b BEZ235 c BGT226 BKM120 PX-866 Temsirolimus b GDC-0941 GDC-0032 GDC-0068 d GDC-0980 c XL147 XL765 c PKI-587 c INK128 b MK2206 b PF-04691502 c INK1117 MEDI-575 Nintedanib Olaratumab Sunitinib Sorafenib Brivanib Aflibercept Axitinib Bevacizumab Motesanib Ponatinib Semaxanib Vatalanib Vandetanib Lenvatinib Pazopanib Cabozantinib e , Foretinib e , Onartuzumab (MET) AZD4547, BGJ398, Dovitinib, E-3810 e , HGS1036 (FGFR) AUY922, Retaspimycin, Tanespimycin (HSP90) Ruxolitinib (JAK) Denosumab (RANKL) PARP BMN-673 CEP-9722 E7016 INO-1001 MK4827 Olaparib Rucaparib Veliparib TNBC 10% 20% 70% HER2 + Luminal, non-HER2 + NCOA3 TNBC Triple-negative breast cancers are ER - PR - HER2 - and show significant, but not complete, overlap with the basal-like subtype of breast cancer (which is defined by differentiation state and gene expression profile). HER2 + breast cancers have luminal features and are characterized by ERBB2 gene amplifi- cation and overexpres- sion leading to a de- pendency on HER2 sig- naling. Luminal (non-HER2 + ) tumors are typically estrogen receptor positive, displaying high ERa levels. These tumors are dependent on estrogen for growth and, therefore, respond to endocrine therapy. SnapShot: Breast Cancer Kornelia Polyak and Otto Metzger Filho Dana-Farber Cancer Institute and Harvard Medical School, Boston, MA 02215 USA Culture and evaluate breast cancer precursor cells at various stages along the differentiation continuum using STEMCELL Technologies’ defined and serum-free culture media, dissociation enzymes, antibodies, cell isolation kits and ALDEFLUOR™. MammoCult™ (Catalog #05620) – the most-published, commercially available medium for the culture of mammospheres and tumorspheres from normal and tumor-derived primary human breast tissue, normal breast cell lines, and breast cancer cell lines. Learn more at www.stemcell.com/mammocult. EpiCult™-B (Human; Catalog #05601) – for the culture and evaluation of human bipotent, luminal-restricted and myoepithelial-restricted mammary epithelial progenitors in the mammary colony-forming cell assay. EpiCult™-C (Human; Catalog #05630) – for the short-term culture of human mammary luminal epithelial and myoepithelial cells. ALDEFLUOR™ (Catalog #01700) – for the non-immunological detection and isolation of viable normal stem and progenitor cells, as well as cancer stem cells, based on aldehyde dehydrogenase (ALDH) activity. Please visit www.stemcell.com for additional information on all products and resources available for breast cancer research.
Transcript of SnapShot: Breast Cancer - Stemcell Technologies › media › files › wallchart ›...
TBL1XR1
Key signaling pathways in breast cancer based on somatic mutation data
Frequency of breast cancer subtypes
USH2A
NF1 RAS
SRC
p53
TBX3
CDK4Cyclin D1/3
MYC
ERa
NCOR1 RUNX1CBFB
GATA3
FOXA1
MYB
pRB
MDM2
AKT
p27Kip1
p16Ink4A
GSK-3
PTENPI3K
mTORC1
mTORC2MAP3K1
MAP2K4
JNK
STMN2
BRAF
MEK1/2
ERK1/2
IGF-1R EGFR HER2 FGFR E-cadherin
*Preinvasive stage**Estimated overall survival (OS) using HER2-targeted therapies
Subtype
*DCIS
Luminal(non-
HER2+)
**HER2+
Stage 5 year OS (%) 10 year OS (%)
0 99 98I 98 95II 91 81III 72 54IV 33 17I 98 95II 92 86III 85 75IV 40 15
TNBC
I 93 90II 76 70III 45 37IV 15 11
Mutation frequencies (%) in all tumors, or just within luminal (including HER2+)
and TNBC subtypes.
Colors indicate tumor suppressors (blue), oncogenes (red), or mutant genes with unclear roles (purple),and lighter shading marks pathway components in which somatic mutations have not been identified.
Top 21 most commonly mutatedgenes in breast cancer
TP53 35 26 54PIK3CA 34 44 8GATA3 9 13 0
MAP3K1 8 11 0MLL3 6 8 3CDH1 6 8 2
USH2A 5 4 8PTEN 3 3 3
RUNX1 3 4 0MAP2K4 3 4 1NCOR1 3 3 1
RB1 3 2 5TBX3 2 3 1
PIK3R1 2 3 2CTCF 2 2 1NF1 2 2 1
SF3B1 2 2 0AKT1 2 2 0CBFB 1 2 1FOXA1 1 1 1
CDKN1B 1 1 0
Gene All (%) Luminal TNBC
10EX
CIT
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CA N C E R RE
SE
AR
CH
EX
CIT
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CA N C E R RE
SE
AR
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SIN C E 2 0 02SIN C E 2 0 02
YEARS OFYEARS OF
ER HER2 PI3K Pathway(PI3K, AKT, mTOR)
Angiogenesis (VEGFR, PDGFR, KIT)
Others(Target)
a Raloxifene is used for breast cancer prevention, not treatment, b mTOR inhibitor, c dual PI3K/mTOR inhibitor, d AKT inhibitor, e also inhibits VEGFR.
TamoxifenRaloxifenea
FulvestrantMegestrol
Toremifene
Anastrozole
Letrozole
ExemestaneEstradiol
PertuzumabTrastuzumab
T-DM1
Lapatinib
NeratinibMM-121
AfatinibCanertinib
Dacomitinib
IGF, IGF-1R
MEDI-573
Figitumumab
LinsitinibGanitumab
BMS-754807CixutumumabDalotuzumab
EverolimusbBYL719
AZD8055b
BEZ235c
BGT226BKM120
PX-866Temsirolimusb
GDC-0941
GDC-0032GDC-0068d
GDC-0980c
XL147XL765c
PKI-587c
INK128b
MK2206b
PF-04691502c
INK1117
MEDI-575
Nintedanib
Olaratumab
SunitinibSorafenibBrivanib
AfliberceptAxitinib
Bevacizumab
Motesanib
Ponatinib
Semaxanib
VatalanibVandetanib
Lenvatinib
PazopanibCabozantinibe, Foretinibe,
Onartuzumab (MET)
AZD4547, BGJ398, Dovitinib,E-3810e, HGS1036 (FGFR)
AUY922, Retaspimycin,Tanespimycin (HSP90)
Ruxolitinib (JAK)Denosumab (RANKL)
PARP
BMN-673CEP-9722
E7016INO-1001MK4827Olaparib
RucaparibVeliparib
TNBC10%
20%
70%
HER2+
Luminal, non-HER2+
NCOA3
TNBC Triple-negative breast cancers are ER-PR-HER2- and show significant, but not complete, overlap with the basal-like subtype of breast cancer (which is defined by differentiation state and gene expression profile).
HER2+ breast cancers have luminal features and are characterized by ERBB2 gene amplifi-cation and overexpres-sion leading to a de-pendency on HER2 sig-naling.
Luminal (non-HER2+)tumors are typically estrogen receptor positive, displaying high ERa levels. These tumors are dependent on estrogen for growth and, therefore, respond to endocrine therapy.
SnapShot: Breast CancerKornelia Polyak and Otto Metzger FilhoDana-Farber Cancer Institute and Harvard Medical School, Boston, MA 02215 USA
Culture and evaluate breast cancer precursor cells at various stages along the differentiation continuum using STEMCELL Technologies’ defined and serum-free culture media, dissociation enzymes, antibodies, cell isolation kits and ALDEFLUOR™.
MammoCult™ (Catalog #05620) – the most-published, commercially available medium for the culture of mammospheres and tumorspheres from normal and tumor-derived primary human breast tissue, normal breast cell lines, and breast cancer cell lines. Learn more at www.stemcell.com/mammocult.
EpiCult™-B (Human; Catalog #05601) – for the culture and evaluation of human bipotent, luminal-restricted and myoepithelial-restricted mammary epithelial progenitors in the mammary colony-forming cell assay.
EpiCult™-C (Human; Catalog #05630) – for the short-term culture of human mammary luminal epithelial and myoepithelial cells.
ALDEFLUOR™ (Catalog #01700) – for the non-immunological detection and isolation of viable normal stem and progenitor cells, as well as cancer stem cells, based on aldehyde dehydrogenase (ALDH) activity.
Please visit www.stemcell.com for additional information on all products and resources available for breast cancer research.
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