Basic Introduction To The Role Of Genetics In Breast Cancer Development And Treatment
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Basic Introduction To The Role Of Genetics In Breast Cancer Development And Treatment
- 1. The role of genetics in the development and treatment of breast cancer? Judith Offman Cancer Prevention Trials Unit WolfsonInstitute of Preventive Medicine Barts and The London School of Medicine and Dentistry
- 2. DNA and mutations Types of Mutations Gene X Gene Gene Gene Gene Adopted from http://teampub.wordpress.com/2008/04/08/dna-chromosomes-and-genes-%E2%80%93-an-overview/
- 3. Genetic factors associated with breast cancer
- 4. Genes associated with breast cancer
- 5. BRCA1 and BRCA2 cancer susceptibility genes
- 6. Founder effect Adopted from ‘Understanding Cancer Genomics’ by National Cancer Institute
- 9. Tumours start with one mutated cell Adopted from ‘Understanding Cancer Genomics’ by National Cancer Institute
- 10. Why are BRCA 1 and 2 important? Why do mutations result in tumours?
- 11. Genes make protein Adopted from illustrations by the ‘Human Genome Program’ of the U.S. Department of Energy
- 12. DNA damage and repair Cell death or tumour development 10,000 events per cell/day DNA repair Mutations
- 13. BRCA1 and 2 function Repair breaks in DNA Cell nucleus BRCA1 BRCA2 gH2AX foci in untreated S-phase cells Mirzoeva and Petrini 2003
- 14. Karyotype Human cells contain 23 pairs of chromosomes
- 15. Karyotype of BRCA- breast cancer HCC1937 cells (BRCA1-) adopted from Grigorova M., et al.. Cytogenet Genome Res. 2004
- 16. Novel treatments and prevention
- 17. New cancer treatments for BRCA patients: PARP inhibitors
- 18. PARP Inhibitor in Cells BRCA BRCA BRCA BRCA No effect PARP PARP PARP PARP Breast cancer cell: BRCA-/- Non-cancer cell: BRCA+/- X No effect X No effect X X Cell death
- 19. In tumours X X X X X X X X X X X X X X X X X X PARP inhibitor
- 20. Clinical trials – monotherapy Trials of PARP inhibitors mainly in BRCA1/2 patients
- 21. Olaparib in a BRCA1/2 mutation carrier enriched study population
- 22. Tumour response to Olaparib in BRCA1/2 mutation carriers 19 BRCA mutation carriers evaluated for tumour response. Fong et al. N Engl J Med 2009; 361:123-134
- 23. Combination with conventional chemotherapy for sporadic tumours