Professor Johann de Bono is developing new molecular targeted therapies to improve the treatment of advanced cancer patients, specialising in drugs for advanced prostate cancer patients. He has a specific interest in biomarker-driven early clinical trials and the parallel development of biomarkers and molecularly targeted drugs.
He has also focused on the development and utilisation of circulating biomarkers, including circulating tumour cells and circulating plasma nucleic acids. These biomarkers are envisioned to be crucial to the optimal clinical development of molecularly targeted drugs, allowing initially patient enrichment and then patient selection to maximise patient benefit and accelerate anticancer drug development.
Inherent to the development of such rationally designed drugs is the concept of personalized medicine, or molecular stratification, to try and give the right patient the right treatment based on molecular data.
Molecular targeted therapies differ from traditional treatments such as chemotherapy in that they are designed to act on only cancer cells and minimise damage to healthy cells. This is the ‘Holy Grail’ of cancer medicine, killing the tumour cell while sparing the cells of the patient’s normal tissue.
Professor de Bono has published a number of papers describing this approach including recent reviews in Nature (de Bono JS and Ashworth A, Nature, 2010) and Nature Reviews Cancer (Yap T, Sandhu S, Workman P and de Bono JS, Nature Reviews Cancer, 2010), and the specific synthetic lethal strategies behind the development of the poly-ADP-ribose polymerase (PARP) inhibitor olaparib in BRCA carrier patients suffering from cancer (Fong et al, NEJM, 2009; Yap et al, The Cancer Journal, 2011).
He was the chief investigator for the first adaptive clinical trial to demonstrate that olaparib has antitumor activity in BRCA mutation carrier patients with ovarian, breast and prostate cancer and that platinum sensitivity parallels to some extent PARP inhibitor sensitivity.
Professor de Bono has been involved in developing more than 100 potential new drugs over the past decade, several of which are now available to patients, and is currently evaluating more than 20 drugs in early clinical trials.
One of these drugs is abiraterone, which was designed and first synthesized by chemists at The Institute of Cancer Research (Jarman M, Potter G, Barrie E). Trials of abiraterone have not only shown that this drug imparts an overall survival benefit to patients with castration resistant prostate cancer, but has also helped clinically qualify circulating tumour cells, demonstrate that ERG rearranged prostate cancer patients have a higher likelihood of benefit and refute the misnomer ‘hormone refractory’ for describing this disease (Attard G et al, Cancer Research 2009; Attard, Cooper & de Bono, Cancer cell, 2009).
Professor de Bono led on the development of both abiraterone acetate and cabazitaxel, taking them from Phase I first-in-man trials to the successful completion of Phase III pivotal trials (de Bono JS et al, NEJM, 2011; de Bono JS et al, The Lancet 2010).
These two drugs are changing our understanding and treatment of advanced prostate cancer, with both of these Phase III trials demonstrating an overall survival benefit to advanced, castration resistant, prostate cancer patients. Both drugs have now been approved in the US and Europe for men with metastatic advanced prostate cancer, and abiraterone became available on the NHS in 2012.
Professor de Bono also recently led a Phase III trial for the drug enzalutamide, which also showed a survival advantage in men with advanced prostate cancer compared to a placebo.