Hi. I'm David Kerr, Professor of Cancer Medicine at the University of Oxford. I am responding to the question, "What single thing would I change about our ossified oncology culture that would improve the cancer patient's lot?"
For me, it is drug development. Clearly, as a medical oncologist, the tools of my trade are the drugs that we use to treat cancers of all types and stages. The drug development process is slow. It's overly bureaucratic. But at its heart, there are some scientific flaws. There's a general truism amongst pharmaceutical scientists that the only way to be confident that a protein is suitable for therapeutic intervention is in retrospect, after a successful drug has been created.
All of us have examples of our colleagues in basic and preclinical science who can wax lyrical about target development using RNA knockdown experiments, xenografts, and complicated tissue culture models, trying to recreate human disease, working in human tissue, and so on. It's a fantastically compelling preclinical package of information, only for it to fall flat when the drug enters a clinical trial. If I were a mouse cancer doctor, I would be king, unquestionably. I can cure almost all of mouse cancer with the existing portfolio of drugs available to me.
Where do we go wrong? I think it's target validation. We know that the scientists involved in pharmaceutical research all go to the same meetings, all read the same journals, and all inhabit the same small island of knowledge. Therefore, they compete secretly and independently in a compartmentalized way to try to validate a target with whatever their medicinal chemists come up with. There is a culture in oncology -- in fact, elsewhere in drug culture -- that the first past the post is the winner. It's first in class, not best in class. That creates a culture of secrecy and urgency, and it means that lots of independent science is being done, but by relatively small groups in a rather clandestine and secretive way.
I am a great fan of open-access science. If we look at how the information highway has changed over the past decade with the use of the Internet, patients are now able to come in with huge amounts of information accessed through the Internet -- free, publicly available information. If we could apply that broad philosophy to drug development, we would increase the hit rate. What do I mean by that?
With 2 great friends and colleagues of mine, Aled Edwards and Chas Bountra, who led the Structural Genomics Consortium in Toronto and Oxford, I wrote a small piece[1] in Nature Chemical Biology several years ago saying that if we could improve target validation, we would increase the likelihood of success of cancer drug development.
The Structural Genomics Consortium, probably one of the best crystallography groups in the world, has put their money where their mouth is. They were responsible for structurally characterizing about 50% of the world's new kinases. During that structural characterization, they developed chemicals that can be used as scaffolds to inhibit these kinases -- chemical probes. They made the purified protein -- the structure of the chemical probes -- freely available to any laboratory in the world that wanted to use it. Instead of having 5 or 6 laboratories working in secret, in parallel, in compartments in big pharma, you could potentially have every interested cancer laboratory in the world using these probes, validating the target, and producing a huge wealth of knowledge that is published and made freely available. That would increase the confidence that, indeed, this is a protein target that is worth pursuing into the clinic.
Let's take it a stage further. If we make these chemical probes available, would it be possible through some public/private partnership to develop clinical probes? Now, these would be best-in-class drugs. It would allow me as a clinician to take a chemical that is proven, safe in toxins, and so forth into a clinical setting, looking for proofs of principle to see how I can validate it in real time in a publicly available trial. Of course, we would anonymize and protect patient names, but we would make the data available throughout the phase 1 trial at each dose level, at each toxicity that we encounter, so that the wider community could see what we were doing. Then pharma could come in with their clever medicinal chemists and come up with drugs that are more convenient, easier to give, with different pharmacokinetic profiles, side-effect profiles, and so on. That would still give us a clearer means of quite rapidly and hugely expanding our knowledge about the target and seeing what we could do within the philosophy of public accessibility and open-access format.
How do we take that into the clinic? There will be all sorts of people in the industry and lawyers throwing up their hands worrying about patients. They are clever people who can deal with that. At the moment, 90% of the drugs that we develop fail. This is a huge waste of time, energy, intellect, dollars, and ultimately patients, goodness gracious me. I think we could do better by thinking through open-access cancer drug development and public/private partnerships. This is bound to be controversial. As always, we would be happy to take any comments. Medscapers, ahoy.
Medscape Oncology © 2014 WebMD, LLC
Cite this: Open-Access Science for Better Cancer Drugs - Medscape - Apr 14, 2014.
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