Notes

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Outline

1	Cancer Strategy: Women’s Cancer, Prostate Cancer Novel Targets for Cancer Therapy: Focus on Resistance RCCoombes Head, Dept Oncology Director, CRUK Laboratories, Theme Leader, Cancer, Imperial College London c.coombes@ic.ac.uk.
2	IES : Sequential Use of Endocrine Therapy
3	Cumulative Hazard Rate - OS
4	Estrogen Receptor-a Phosphorylation Sites
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6	[¹¹C]choline CH3 CH3---N⁺---CH2---CH2---OH ¹¹ CH3 [11C]choline [11C]-phosphocholine [¹¹C] betaine (liver, kidneys)
7	[11C]choline-PET image of breast cancer
8	Choline activity normalised to proliferation (Ki_cho/AUC_FLT)
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10	ERα Serine 118 Phosphorylation in Breast Cancer Mediated by MAPKinase, Cdk7, ?GSK3β Mutation markedly impairs function Correlates with p-MAPK, p-p90RSK Increased in some patients becoming resistant to tamoxifen Reduced by inhibition of EGFR in the some, but not all, responders
11	Phosphorylation of Serine 118 is Mediated by MAPK and Cdk7
12	Cyclin-dependent kinase Cdk7 Stimulates ERa Activity
13	Is Cdk7 responsible for ER Phosphorylation via the residual estrogen following AI’s?
14	Collaboration with Chemistry Imperial Collge Medicinal chemistry PhD programme Small molecule programme grant CADD facility Structural programme and bio-informatics Probe programme for PET
15	Inhibitors in CDK7
16	BS181 Characteristics CDK7 CDK2
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20	FoxM Regulates G1-S and G2M transition Cytoplasmic during G1-S Activated by MAPKinase phosphorylation and this results in nuclear translocation during G2M
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22	"FoxM1 is a physiological regulator..."
23	Hypothesis Tamoxifen resistance accompanied by increased MAPKinase
24	Gamma Secretase as a Potential Mediator of Resistance
25	-GS Activity Increases with Inhibition of MapKinase-
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31	Target Identification in Prostate, Ovarian, Lung cancer
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34	Drug development to reverse platinum resistance: Ovarian Cancer
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37	"Thanks to"