Cancer. People speak about this extraordinarily diverse and complex group of diseases as if they were one illness and ask us impatiently when we are going to “cure” it.
The reality is that many researchers, myself included, don’t believe we will ever cure cancer. For a start, trying to develop a single “cure for cancer” would be like trying to develop a single cure for Aids, depression, the flu or a broken leg. We’re making progress in designing treatments for specific cancers, but they adapt quickly, with many of them evolving in such a way that they can resist being killed by drugs.
This presents an enormous challenge. Some of the best treatments will only work for a limited time before resistance kicks in. But understanding resistance will help us to defeat it.
One of the ways we investigate resistance is by studying cell lines. These are cancer cells that were taken from patients and then kept alive in the lab. These cells, which are fed with a sugar solution and grown in plastic flasks, are a long way from a human with the disease. But they let us quickly and easily get to know how a cancer works, and how its behaviour can be changed by a gene or protein change, or a drug.
Some cell lines are grown in the constant presence of a particular drug. Most of the cells grown this way will die, but a few survive, and in time, these resistant cells will take over. It’s like bands of resistance fighters regrouping after their army has been destroyed.
Cell lines that have been conditioned to become resistant over time in this way are very valuable because they mimic what happens in patients who stop responding to therapy. They help us find out how cancer cells changed when they became resistant, and test whether new drugs will work in resistant as well as sensitive patients.
But the most valuable research we can do is when patients opt to donate their tumour to research after surgery, which means we can look at how cancers from “responders” are different from cancers that were taken from people for whom the drugs had stopped working.
Some cancers become resistant by switching on special survival proteins when they sense danger. One such protein is PI3K, which is activated when cancer cells are attacked by a drug. PI3K, once activated, goes on to activate other proteins that have other effects that help cells survive under stressful conditions. One will trigger cells to reproduce more, another will hack into the body’s healthy blood supply to hijack nutrients, and another will block the signals that tell a cell to commit suicide when it gets old.
Drugs are being designed to block this kind of chain reaction. For example, last year a clinical trial showed that a drug called Afinitor could potentially thwart resistance caused by the PI3K pathway in some cancers, by blocking the action of one of the chemicals in this pathway.
Another way cancers avoid being killed by drugs is by using “pump proteins” that eject the drug from the cell. One such protein is called P-gp, and it evolved as a way to protect us against infection. Its normal function is to push pathogens such as bacteria out of our cells before they have a chance to make us ill.
Scientists have been trying to block the action of the P-gp pump for decades, but it has turned out to be difficult to interfere with it without harming the patient. However, every study that hasn’t quite worked has brought us one step closer to a solution. Last month, an article was published in the journal BMC Cancer reporting that a new drug may be able to reverse chemotherapy resistance caused by P-gp. More tests will be needed before we know if this drug can be given to patients, but the research is encouraging.
I said at the start of this article that I don’t believe cancer will be cured. Some cancers will always find a way to develop resistance. But I do believe there will come a time when we know these resistance mechanisms so well that there will always be a new therapy, and cancer will become a long-term illness, treated with one drug until that drug stops working, at which point the patient will be switched to a different drug.
We have made dazzling progress in the past few decades with the invention of targeted drugs that don’t have the side-effects of chemotherapy, and this improved quality of life for patients will only get better with time. The future is full of challenges, but also full of hope.
Naomi Elster is a writer and scientist researching for a PhD in cancer medicine at the Royal College of Surgeons, Ireland, supported by the Irish Cancer Society
Barbara Jacoby is an award winning blogger that has contributed her writings to multiple online publications that have touched readers worldwide.