Has there been anything recent on Dr. Gillison's trial on the PDl-1 pathways and antibody able to inhibit tumors' ability to shield itself from our immune system? Brian mentioned this some time ago noting that an article would be published on this in a few months.

The first of the drugs related to this are already through the FDA and available. Opdivo was the first to hit the market and exploit this opportunity. My guess is that it will be used in combination with other, in process, monoclonal antibodies as none of these are a win all by themselves in everyone. The science paper on the second trial should be out soon, (that OCF helped support). But the FDA didn't wait to fast track this as it had good clinical results with minimum side effects. It had efficacy in people who had failed primary treatment including radiation and platinum chemo, or who were in recurrence, often with lung mets.

The trend in cancer treatment and in cancer research right now is to get away from the big hammer treatments like radiation and systemic chemotherapy that are the current mainstay ideas. We are looking at a cancer cell and finding mechanisms to mess with just one part of what it does to stay alive and cause havoc. In our world, Erbitux was the first of these to hit the market. It was a drug that inhibited EGFR or episomal growth factor receptor. This essentially plugged at receptor site on the outside of a cell where a messenger protein carrying the message "replicate" plugged in. No message, not so much activity. Now we can open up a signaling pathway; programed cell death ligand -one, that allow the immune system to see something that was hidden before, this is an immune checkpoint inhibitor.

None of these by themselves will do the whole thing in everyone. But the pipeline of these kinds of drugs in the future is rich and full, and we are going to see more things, in the near future, like angiogenesis inhibitors, which will likely not be far behind this. These will prevent the tumor from attracting new capillaries to it to sustain itself. In a few years we will have many more ways of interfering with a malignant cells ability to function, or even exist. Most of these have low side effects, which makes them quite attractive.

A really simple analogy would be what does it take for someone to keep a car from making it to the next city? You could plug up just the gas tank filler. Wouldn't destroy the car, but it wouldn't go very far once it ran dry and couldn't have more gas put into it. You could take out the spark plugs. All the gas in the world won't help you if you can't ignite it.... and so on. You keep interfering with the car in so many ways that it is eventually worthless. This is the kind of treatment approach that would make cancer less of a killer disease and more of a manageable one that you could live with at some level, just as AIDS has become with retroviral drugs today.

The earliest example of a commercial drug built around this idea was designed for lung cancer and called Iressa. It was amazing, but at the time thought to be a commercial failure. 10% of the people that got it had a 100% NED status after getting it. So it wasn't the magic bullet. And initially they didn't know why it worked in those people and not others. But a few years after it got approved they started looking at the genome of those that it worked in (Now we had mapped the human genome and looking at a single individual had gotten to a place that was moderately affordable) and found some similarities. Now you get your genome mapped and before they decide to do something else they see if you match the profile of someone that this drug worked in. This is the future of targeted therapies. No big hammers, but lots of small wrenches being thrown into a cancer cell's ability to exist.

This is great news! And so very encouraging. Thanks, Brian!

Just a few minutes ago, I saw a great commercial on Opdivo! Wow! the research that OCF helped support has really moved fast!