How cancer hijacks healthy cell functions

What’s actually going on inside the body when a cancer forms? What is driving the disease, how does it subvert our normal healthy systems, and how does it begin in the first place? Chris Smith went to see Cancer Research UK Cambridge Institute’s Giulia Biffi…

Giulia - Cells in a normal tissue maintain the structure and function of the tissue by either expanding through a process called cell proliferation or by reducing in size through a process called cell death. Cancer hijacks these two processes leading to increased proliferation or impairment of cell death.

Chris - Why does that happen in the first place, though? What changes to make the cells begin to behave like that?

Giulia - One mechanism that leads to cancerous growth is through mutations in genes that are components of the DNA, which is the blueprint of a cell that tells a cell, you are a lung cell, or a liver cell, or a skin cell. Typically, mutations occur in two different types of these genes. One set of genes, for example, has as a function suppressing the growth of the cancer and has a role in cell death. Those are called tumour suppressor genes. Then, the other set of genes are called oncogenes. Those genes acquire mutations that lead to hyperactivation of signalling downstream. So the cancer would grow, but also the cancer can reprogramme cells of the normal organ and reprogramme them in a way that would support its growth and also spread it to other organs. It's a crosstalk relationship between these two different components.

Chris - That's intriguing. So the cancer cells can get non-cancerous cells to start to help them. It's almost like in a war you persuade the local population who are not in theory on your side to start helping the enemy?

Giulia - Yeah. The cancer cell can either prevent some cells from doing their function in fighting the cancer or can encourage other cells, other normal cells, to help further proliferate or disseminate to other sites.

Chris - Do they do that by 'talking' to the cell next door by reaching out and touching it? Or is that because they send chemical signals? Or both?

Giulia - It's actually both. There can be communication via cells through secreted factors, or there can be communication via cell-cell interactions that would lead a cell to, for example, migrate or invade a blood vessel and then colonise a different organ.

Chris - And presumably, if this is going on, it can also frustrate our efforts to treat the tumour because it could limit access of drugs to the cells you want to kill or other things that would normally control cell growth can be prevented?

Giulia - Yeah, so access to drugs can be a problem also because cells that are not the cancer cells could uptake those drugs and this would reduce the concentration of the drug and wouldn't affect the cancer as well as if those cells weren't around.

Chris - What about when the cancer spreads to a distant site, though, in the body? Because I remember being really struck by a paper published in one of the big science journals a few years ago showing that before a cancer spreads to, say, the lung, you can see that the cells in the lung start to change their behaviour and even bring in other cells from other bits of the body that are not cancerous and then the cancer spreads. It's like a bird making a nest remotely that it then moves into?

Giulia - If you can imagine a cancer growing in a particular organ, it will affect the function of that organ. But also that will affect systemically the whole host, the whole person. Other organs may also be reprogrammed from a distance by the cancer in a different organ. The cancer would benefit from these changes and be better able to grow in that different organ.

Chris - So we've got local effects where the tumours are growing, they're expanding, putting pressure on tissue and that can do harm. They're subverting local tissue into changing its behaviour, which can do harm and also stop drugs doing their job. They can also do that at remote sites in the body by understanding that malignant process. Does that give us clues as to how we might have an 'in' to try and tackle cancer?

Giulia - Intrinsically, some cancers are more dangerous than others but, broadly speaking, cancers are more dangerous when they are at a late stage of development: they have already spread to other organs. You can imagine that if you have a cancer that's localised to one organ, it could be more easily treatable. For example, it could be surgically resected, removed. But if the cancer is in multiple organs it's much more difficult to target. If we are, for example, to identify this cancer at earlier stages with early detection strategies, then we already have a better window in which we can intervene with the patient and help them.

Chris - Are there any clues that are emerging from research like yours, though, that tell us new ways that we might be able to combat cancers.

Giulia - Therapeutically, well, by better understanding how these cancer cells are talking to the normal tissue and reprogramming it to support its growth and spread into other sites, then we will be able to target those interactions and more effectively design treatments that are targeting multiple tumour promoting effects.

Chris - When a person gets cancer, by the time they're diagnosed with, say, a pancreatic cancer like you work on, how long have they probably had that disease for before it takes off and becomes clinically manifest and they're off to the doctor?

Giulia - Cancers may have different windows from when they start arising until they are diagnosed, but typically it's years. I think there is a really big window of opportunity if we were to identify ways to detect it earlier. In addition to early detection, methods that are preventative are also good strategies. For example, colonoscopies, endoscopy procedures that would identify precancerous lesions that can be removed, those are effective, even more effective than early detection strategies. For example, here in Cambridge, Professor Rebecca Fitzgerald has designed and implemented the cytosponge that allows us to identify our oesophagus, which we can treat and intervene on, and then these patients wouldn't then progress to oesophageal cancer.