Following on from the success of Senectus Therapeutics Ltd, where the company has just progressed to a second round of funding to identify targets inducing senescence for cancer therapy, a second CR-UK funded consortium around the identification and validation of cancer stem cell specific drug discovery targets established by CRT has recently been awarded seed funding. Now CRT has begun investigating areas of “hot” cancer science to identify other potential areas where the ground breaking research being undertaken by CR-UK scientists can lead novel drug discovery efforts in industry and we are currently seeking industrial collaborators and partners
Epigenetics: A broad portfolio of research funded by CR-UK at a number of UK Institutes
CR-UK funds over £23m worth of science in the area of epigenetics, from basic understanding of how the process of histone and DNA modification affects cancer cells, through to a number of hit-to-lead programmes on inhibitors of epigenetic targets. This work is helping us to understand how this promising group of targets can better be exploited in the clinic through improved understanding of the disease linkages as well as defining which combinations of agents would work to improve outcome. As well as this, a number of more novel targets are being identified and validated by some of the world’s leading scientists in this field in order to support drug discovery efforts around CR-UK.
What’s unfolding in the ER stress area?
In the field of unfolded protein response and ER stress, CR-UK is fortunate to have a drug discovery group with a proven track record. Paul Workman’s Cancer Therapeutics Unit at the Institute for Cancer Research were pivotal in the discovery of HSP90 inhibitors which are now in phase II trials as well as having a number of partnered and unpartnered programmes earlier in the discovery cycle. To add to this, CR-UK fund a significant amount of basic research in the area which is identifying and validating targets that could be fed into an alliance in the field. These targets include novel ER stress and unfolded protein response targets as well as targets in the related fields of autophagy and protein degradation.
Tumour Microenvironment: It’s getting hot in here
The tumour microenvironment is attracting renewed interest with groups around the world attempting to understand how the tumour subverts the stromal cells of the host to aid in its survival and growth. Cytokines are a key modulator in this and CR-UK’s Fran Balkwill is a world leader in this field. CRT is pulling together a number of researchers around the UK. CR-UK invests heavily in this area of research and have, together with Professor Balkwill, defined a smaller group who would be ideal to study the interaction between the tumour and stromal cells, the role of cytokines in this and the therapeutic targets and key interactions with approved drugs. CRT has also identified a group to study the other key area of interest within the tumour microenvironment; namely the possibility of converting the adaptive immune system infiltrate within the tumour from a permissive to a suppressive state.
UPS under the spotlight
Ubiquitin Proteasome System (UPS) and ubiquitin-like modification is rapidly being understood to signal to more than just the proteolytic degradation of a tagged protein. The major barrier to drug discovery in this exciting area of science is two-fold; the identification and validation of specific cancer-associated targets and the development of specific tools for prosecuting a drug discovery cascade analogous to those developed for phosphorylation. CRT has been able to tap into the work of CR-UK funding of over £12m to identify the key leaders in this field and has a portfolio of targets at various stages of the validation pathway. This programme would aim to complete the validation of these targets in combination with the production of the ubiquitin focussed tools, allowing high throughput screening, generation of tool compounds and proof of concept in vitro.
Leading the way in DNA damage response
CR-UK is a world leader in the field of DNA damage response, with the London Research Institute boasting researchers such as Sir Tim Hunt, Steve West and Neil McDonald who are key opinion leaders in the understanding how DNA damage repair occurs. This basic research is supplemented by a significant CR-UK project spend around the country, including groups such as Laurence Pearl and Antony Carr at Sussex and Ricky Sharma et al in Oxford. In addition to this, CR-UK support the work of the drug discovery group based at the Northern Institute of Cancer Research under the leadership of Herbie Newell, who have prosecuted a number of DNA repair targets to date, including inhibitors of PARP, currently in phase II trials, and collaborations around DNA-PK and ATM. This group are closely associated with the Experimental Cancer Medicine Centre in Newcastle where both Ruth Plummer and Hilary Calvert have been involved in numerous DNA damage response first-in-man trials.
Partnering to create a shared future
Building on our highly successful alliance with AstraZeneca in cancer metabolism and academic consortia such as Senectus, which we seed funded, CRT is exploring new ways to bring together the complementary strengths of academia and industry to discover and develop innovative cancer drugs and diagnostics.
For further information please contact Dr Phil L'Huillier at firstname.lastname@example.org.