Achievements
Chief Executive, Professor Alan Ashworth
The ICR’s record of achievement in understanding the genetic basis of cancer is second to none, and our scientists continue to make significant progress.
Achievements in 2009/10 include:
- We performed the first Phase I trial of an oral PARP inhibitor, Olaparib, in patients with cancer. We demonstrated that this treatment is safe and well tolerated, and in a focussed expansion we were the first to show significant activity for this treatment in patients with recurrent BRCA associated ovarian cancer. These trials are the first successful examples of personalised medicine using a synthetic lethality approach that targets a patient’s tumour specific molecular defect.
- Genome-wide association studies identified three genetic variants that increase the risk of developing acute lymphoblastic leukaemia (ALL), the most common cancer in children. These results are the first evidence that genetic makeup plays a major role in the risk of ALL and will provide insight into how the disease develops.
- Genome-wide association studies have provided insight into the development of brain tumours identifying five genetic variants that can increase the risk of developing Glioma, the most common form of brain cancer.
- We have described how Rho GTPases, a key group of proteins, involved in the spread of tumours, are activated. Three-dimensional structural analysis revealed the mechanism through which members of the DOCK family activate Rho GTPases. The results provide a basis for the development of drugs that can target DOCK proteins and block metastasis.
- By applying innovative computer modelling to studies of cell movement, ICR researchers have for the first time been able to investigate the timing and duration of key cell-to-cell signalling processes. This approach will be important in understanding how different cell populations communicate with each other during cancer development and progression.
- Studies on drugs used to treat Melanoma showed that targeting the BRAF protein should only be undertaken in patients with a faulty version of BRAF. These results underline the importance of personalising treatment to those who are likely to best benefit from BRAF selective inhibitors.
- We have discovered that having too many copies of the FGFR1 gene can cause resistance to the widely used drug Tamoxifen and other hormone-based therapy in breast cancer. By identifying the importance of the FGFR1 gene, these findings have revealed a new drug target for treating breast cancer in patients who would otherwise have a poor outcome.
- The CR-UK Cancer Therapeutics Unit has developed GDC-0941 – a new drug which inhibits the PI3 kinase pathway – that reduces the most common form of brain tumour by 98% in laboratory tests. As a result, Phase I clinical trials are now being conducted in the UK and USA.
- We have found that in bowel cancer cells carrying the inherited mutation of either MLH1 or MSH2 genes (which prevent cells from repairing damaged DNA), blocking the action of another type of DNA repair protein stops the cells repairing DNA damage. Targeting cells already carrying one of these mutations with a drug that blocks this second part of DNA repair could be an effective personalised treatment for bowel cancers caused by these mutations.
- Results from clinical trials in early breast cancer have found that the effectiveness and patient-reported chronic side-effects of radiotherapy, are not any worse when given as
a lower total dose, delivered in fewer, larger treatments compared with the standard of a higher total dose delivered over a longer time. As a result, radiotherapy treatments
can be changed so that women spend less time in hospital and the cost to the NHS is reduced.
For further information on the ICR’s achievements see:
