Much of the progress in cancer survival over the past few decades can be credited to life-saving and life-extending drugs.
But what goes on behind the scenes in the lab? How do scientists discover new drugs, and how can these be ‘designed’ to home in on cancer? What makes a good medicine, and what are the challenges we face?
In our latest Google Hangout, we were joined by two experts in this field – Professor Raj Chopra from The Institute of Cancer Research in London, and Dr Allan Jordan from our Drug Discovery Unit at the Cancer Research UK Manchester Institute to explore these questions.
World leaders in their fields, they began by discussing how the idea for a new drug can come from many different avenues – from researching the biology causing cancer, and from studying published research carried out by other scientists around the world.
Jordan is keen to point out the advantages of working at a university or charity-funded research institute such as the Cancer Research UK Manchester Institute. “It puts you a couple of years ahead of the game. You see research as it’s emerging from the laboratoriesrather than waiting for it to be published in a journal,” he said ”But the downside is that no one else has done the experiments, so it’s high risk.”
The first big step is choosing a molecule to design a new drug to act upon – known as ‘target selection’. Jordan explains more: ”Every process that happens in the body is controlled by an on and off switch somewhere. You can visualise it as lots of locks and keys, and by locking or unlocking them we can control those processes.”
Drugs can be designed in exquisite detail to make them fit a specific ‘lock’. The ideal drug shuts off processes that are vital for cancer cells to survive, but doesn’t affect healthy cells in the body – the cause of side effects.
Once a target has been chosen, that hard work begins. The target first has to be ‘validated’. And plenty of drugs fall at this first big hurdle.
Cancer cells are very complicated, and sometimes research only reveals part of the picture. ”Doing things in different ways might give different results, and you need to do experiments many times to be sure,” says Jordan.
“But we have to be very clear that the targets we go for are true drivers of cancer and that there’s good quality pre-clinical research supporting it,” says Chopra.
Just making sure the chosen target is vital to cancer’s survival can take between seven and eight years.
Even after researchers have chosen and validated a target, it’s not all plain sailing. The next step is working out how to hit the target with something that can be given to people as a medicine.
“You need a drug that’s going to be easily absorbed, and will circulate around the body in the blood and get to the tumour,” Chopra explains. ”You also want to make sure it’s not broken down rapidly by the liver or kidneys.”
Furthermore, cancer patients often take more than one drug at a time, so potential interactions with other medicines need to be considered at this point too.
The chemistry can be really tricky to get right, and there are many challenges to refining and adapting a drug to reach a point where it will reach the tumour in levels high enough to kill cancer cells.
”Computers help us design them but it’s still often down to trial and error,” says Jordan. “We might try a drug design but a key bit breaks off, so we have to refine it to make sure that doesn’t happen. Sometimes the chemistry just means the drug simply won’t work, and it’s back to the drawing board, which is frustrating, but that’s drug discovery for you.”
And of course there is the final challenge of improving what is already available to cancer patients. According to Chopra there’s no point in making a medicine unless it’s different and can add value over and above existing therapies.
You can watch it in full on YouTube. And keep your eyes peeled for the second part – our next Google Hangout will focus on testing new drugs in patients, and will be broadcast in the next few weeks.
If you have any feedback about our Hangouts or would like to suggest a topic for a future discussion, please leave us a comment below.