2012 © Institute for Molecular Medicine Finland FIMM
Novel therapies against breast cancer
Mission
We aim to develop novel therapies against breast cancer through a deeper understanding of breast cancer biology.
Background
Breast cancer is the most common malignancy in women. Roughly 3 out of 10 women will be diagnosed with breast cancer in their lifetime and one of them will die of the disease. About 10% of all breast cancers run in families largely owing to heritable mutations. Surprisingly, almost half of them can be attributed to defects in genes regulating the homologous recombination (HR) pathway of DNA repair: BRCA1, BRCA2, PALB2, and RAD51C. While few therapeutics have been developed that can effectively target primary tumors with mutations in HR genes, such as PARP (Poly-(ADP)-Ribose Polymerase) inhibitors, tumors usually develop resistance. Therefore, new drugs and drug combinations are needed to better treat such patients.
Projects
- We use high throughput screening technologies to identify new therapeutic targets for cancers with mutated BRCA1, BRCA2, or RAD51C, and tumor suppressors contributing to therapy resistance.
- We aim to understand the pathogenesis of RAD51C-mediated tumors using a mouse model developed previously by Kuznetsov and colleagues. We hope to shed light on the underlying causes of the association between homologous recombination and predisposition to breast cancer.
Group Members
| Sergey Kuznetsov | Group leader | sergey.kuznetsov@helsinki.fi |
| Annabrita Schonenberg | Lab technician | annabrita.schoonenberg@helsinki.fi |
| Sonja Koopal | Lab technician | koopal@mappi.helsinki.fi |
| Sharif Igbal | Master student | sharif.iqbal@helsinki.fi |
| Manuela Tumiati | PhD student | manuela.tumiati@helsinki.fi |
| Yuexi Gu | PhD student | yuexi.gu@helsinki.fi |
| Pauliina Munne | Postdoc | pauliina.munne@helsinki.fi |
Contact
You can call us at +358-9-19125749.
Funding
Funding is generously provided by the Sigrid Juselius Foundation, Finnish Medical Foundation, Academy of Finland, Biocenter Finland, Cancer Society of Finland, Helsinki Biomedical Graduate School (HBGS), Helsinki Graduate Program in Biotechnology and Molecular Biology (GPBM), and Finnish Cultural Foundation.
Selected publications |
- Kuznetsov SG, Liu P, Sharan SK. Mouse embryonic stem cell-based functional assay to evaluate mutations in BRCA2. Nat Med. 2008 Aug;14(8):875-81.
- Li L, Biswas K, Habib LA, Kuznetsov SG, Hamel N, Kirchhoff T, Wong N, Armel S, Chong G, Narod SA, Claes K, Offit K, Robson ME, Stauffer S, Sharan SK, Foulkes WD. Functional redundancy of exon 12 of BRCA2 revealed by a comprehensive analysis of the c.6853A>G (p.I2285V) variant. Hum Mutat. 2009 Nov;30(11):1543-50
- Philip S, Swaminathan S, Kuznetsov SG, Kanugula S, Biswas K, Chang S, Loktionova NA, Haines DC, Kaldis P, Pegg AE, Sharan SK. Degradation of BRCA2 in alkyltransferase-mediated DNA repair and its clinical implications.Cancer Res. 2008 Dec 1;68(23):9973-81.
- Kuznetsov S, Pellegrini M, Shuda K, Fernandez-Capetillo O, Liu Y, Martin BK, Burkett S, Southon E, Pati D, Tessarollo L, West SC, Donovan PJ, Nussenzweig A, Sharan SK. RAD51C deficiency in mice results in early prophase I arrest in males and sister chromatid separation at metaphase II in females. J Cell Biol. 2007 Feb 26;176(5):581-92.
- Kuznetsov SG, Haines DC, Martin BK, Sharan SK. Loss of Rad51c leads to embryonic lethality and modulation of Trp53-dependent tumorigenesis in mice. Cancer Res. 2009 Feb 1;69(3):863-72
- Biswas K, Das R, Alter BP, Kuznetsov SG, Stauffer S, North SL, Burkett S, Brody LC, Meyer S, Byrd RA, Sharan SK. A comprehensive functional characterization of BRCA2 variants associated with Fanconi anemia using mouse ES cell-based assay. Blood. 2011 Sep 1;118(9):2430-42