CellCentric has pioneered in the area of epigenetics, to find new ways to treat cancer. We have validated p300/CBP as two key twin proteins that when inhibited, can stop disease progression. We have developed CCS1477, a small molecule inhibitor that stops the function of the two proteins. The drug, taken as an oral capsule, is now in clinical trials for endocrine resistant prostate cancer, haematological malignancies (multiple myeloma, AML, lymphomas), as well as tumours with specific molecular drivers.
A summary of the translational work, from lab to prostate cancer patients, has published this week in the high impact journal, Cancer Discovery:
The paper outlines how targeting p300/CBP impacts key signalling pathways involved in prostate cancer. It gives details of the drug that has been developed by CellCentric, that binds into the conserved bromodomain of both p300 and CBP to inhibit their activity. The data presented goes on to show how results from the lab translate into effects seen in patients, with a focus in this paper on men with prostate cancer.
The collaborators and co-authors of the paper are from the Institute of Cancer Research, London and the Sidney Kimmel Cancer Centre (TJU), Philadelphia. Researchers from multiple specialist contract research organisations (CROs) are also included. It takes a mighty team effort to go from scientific concept to early data in patients; academic researchers, consultants, advisors, CROs, service providers, hospitals and funders. CCS1477’s current clinical evaluation involves over 200 people.
Co-lead author, Professor Johann de Bono, Professor of Experimental Cancer Medicine at The Institute of Cancer Research, London, and Consultant Medical Oncologist at The Royal Marsden NHS Foundation Trust, said:
“Our study offers a potentially exciting new approach to treating prostate cancer. For the first time, we have shown that blocking two proteins known as p300 and CBP with a new targeted drug can disrupt signals that help fuel the growth of prostate cancers.”
Study author Dr Adam Sharp, Team Leader in Translational Therapeutics at The Institute of Cancer Research, London, and Consultant Medical Oncologist at The Royal Marsden NHS Foundation Trust, said:
“We have shown that a new targeted drug can block androgen receptor signalling – which plays a key role in prostate cancer – as well as its treatment-resistant altered forms and another important cancer gene known as c-Myc.
“Being able to target both androgen receptor signalling and its adaptions is an important step forward, as it helps us tackle the huge challenge posed by cancer’s ability to evolve resistance to modern hormone treatments.”
Professor Paul Workman, Chief Executive of The Institute of Cancer Research, London, said:
“These early clinical findings are very encouraging. It is exciting to have validated a major new drug target in prostate cancer through collaborations with industry and to already have a promising, mechanistically innovative, ‘first-in-class’ drug agent undergoing clinical trials.”
Dr Jonathan W. Simons, Prostate Cancer Foundation President and CEO, said:
"This marks another great leap ahead in precision medicine to help men with advanced prostate cancer. PCF is proud to have funded this research that has launched this promising therapeutic into clinical trials, bringing us closer to our mission to eliminate death and suffering from prostate cancer."
Dr Will West, CEO of CellCentric, added:
‘From our foundation in epigenetic research, to publishing translational research for our first of its kind drug, it has been an incredible team effort. It has been great to work so closely and openly with The Institute of Cancer Research and The Royal Marsden, but also to the many other researchers and clinical centres now testing our drug across the UK.’
Prostate Cancer Foundation