"Big Data, Genetics and Translation"

I’ll be following @ewanbirney et al’s foray into drug target validation with great interest: http://t.co/XMpDPCElLC
— Daniel MacArthur (@dgmacarthur) March 27, 2014

http://genomeinformatician.blogspot.co.uk/2014/03/big-data-genetics-and-translation.html

"Drugs act on these targets. Drugs are often small molecules and sometimes proteins, like antibodies, that will change the activity of a biological target. A drug has to be able to enter the body, do what it was designed to do and not mess around doing other things. Pharmaceutical companies are really good at making these.

Clinical trials involve giving a new (or repurposed) drug to a group of consenting people. They are jaw-droppingly expensive. Unfortunately, the vast majority (90%) of drugs ultimately fail to make it through clinical trials. A large proportion of those fail because the information on which they were based, from right at the start – the target protein– was not quite right.

What’s the problem? In short, it is that a billion-dollar phase III clinical trial is a very expensive way to discover that your drug wasn't changing the right target."

How do you make it better?

"Clearly, validating those biological targets is extremely important and it can be done a lot better. What the CTTV is aiming to do is change the landscape for the initial phase of drug discovery by pooling our knowledge and resources to improve target validation.

GSK realised that this is not something that they (or any other commercial organisation) can do easily in house. Wisely, they decided that this work is best carried out pre-competitively, in the public domain. Around a year ago, members of GSK’s senior leadership came to visit the Genome Campus to explore a way forward, and the CTTV concept was born."
(...)
"At what point can one say, definitively, that this protein is a good target for a drug to act on to change the course of a disease?

To resolve this you would ideally create a specific perturbation that changes a specific molecule, verify its safety in humans and give it to people with the disease. In short, develop a drug. But the CTTV aims to get a good handle on target validation without actually making drugs, so what information are we working with, and what are we hoping to deliver?"

 

http://genomeinformatician.blogspot.co.uk/2014/03/big-data-genetics-and-translation.html

"Not to get too geeky, but I’m particularly excited about the CRISPR/Cas9 technology (like most experimentalists) because they make it possible to introduce specific mutations into cell lines. This should be particularly powerful in oncology, where systematic cancer sequencing efforts are giving rise to a number of robust targets. Cancer has been transformed by the ability to more systematically find oncogenes and tumour supressors via sequencing, leading to targeted therapies such as BRAF inhibitors. The question is: which ones in a now established cancer cell do you need to target to slow (or stop) its growth?"

Source.