Dr Joan Massagué, Sloan-Kettering Institute
Kat - Probably the biggest issue in cancer and one that causes around 9 out of 10 cancer deaths is the fact that cancer spreads around the body, forming other tumours elsewhere. This is a process that scientists call metastasis. Now we’re joined here at the NCRI Cancer Conference by Dr. Joan Masague from the Memorial Sloan-Kettering Cancer Centre in the New York and he’s working on trying to understand how cancers spread and how we can tackle it. So, hello, good evening, Joan.
Joan - Hello.
Kat - So, let’s start by going back to basics. What do we mean by a cancer spreading? What's going on here?
Joan - Cancer as we know is an abnormal growth that is generated, initiated by just a few cells in a human tissue. It could be the breast. It could be the prostate, intestine, anywhere. A few cells that have accumulated mutations and these mutations allow these cells to begin to break the rules that keep the healthy normal growth of tissues. These rules include not only growing and proliferating correctly, but also staying put. The cancer cells have the ability to move away, to walk away, and as the tumour grows and the blood vessels are attracted to feed the growth of this tumour, cancer cells find their way into the circulation. Circulation carries them away. In distant organs these cells may, by virtue of their ability to walk, to infiltrate, to invade, come out of the circulation again, enter the distant tissue that could be the liver, the lung, the bone marrow, the brain, and try and resume cancer growth there. This whole process is what we call metastasis.
Kat - So, we’ve got these naughty cells, not knowing that they should stay in one place and spreading, and forming new tumours, why is this such a big problem in cancer? Why is this? Why does this make cancer so hard to treat?
Joan - Of course, with the spread of cancer, we have not one tumour only that is localised and can be removed in the operating room, we now have other tumours in many other places. Not only that, but these tumours are created by the nastiest of the nasty. Those cells that were able to leave the primary tumour, the origin tumour, find their way to distant places, resist having invaded an organ, a tissue that they're not accustomed to, and so forth. So, the cells that undergo this process are more aggressive and are going to be even more resistant than the original tumour to any therapy that we try.
Kat - These are really evil, nasty cancer cells then. So, I remember reading about a guy over 100 years ago – Paget I think his name was – who had the idea of the seed and the soil. So the cancer cells that spread are like the seed and they go around the body looking for soil they like to grow in. What do we know about the types of places that cancer cells spread? Is it the same places like a cancer will always go to, the brain or the lung, or is it different?
Joan - Well, we know from patients who have cancer that every type of cancer has a different predilection for metastases to different organs. And so, the question is why? The way we now think about these, based on the results of research is that of course, when cells leave a tumour, they go everywhere. The circulation takes them everywhere. What we mean by growing in one place is that they die everywhere, but they die less. They have more chance in a given organ than another because they are somehow primed to thrive there with more probability than in another distant organ.
Kat - So I guess this is a bit like a dandelion or something, sending all of these seeds out and most of them will never ever grow, but just a few of them do. What do we know now about why some of these cancer cells do manage to grow in some places? What's going on?
Joan - We know the about the molecules and genes, and processes that allow these cells to go through a series of bottlenecks that they face in order to invade a given organ. First, they have to come out from the circulation into that organ. The blood vessels are different organs, so the cancer cells in the circulation to begin with, they need different skills to get into an organ or another. Second, they have to resist the shock of entering an organ that they have never seen before. And so, that immediately selects for cells that were prepared to deal with that new environment and finally, to overtake. Not just to resist, but actually, to take over that organ. That too, needs a different set of skills. So, we’ve identified genes and molecules that allow the cancer cells in any given organ to go through each one of these bottle necks.
Kat - And of course, it’s great to identify all these factors, the molecular factors, the genes, and the molecules. How are we trying to turn this knowledge into new ways of treating cancer that has spread because it still does claim so many lives?
Joan - Yes, and 90% of lives claimed by cancer is through this process of metastasis. We are learning a lot about the biology and about these different molecules, and the steps that I was talking about. What we want at the end is the common nexus, those molecules and genes that allow the majority of cancer cells to be metastatic to many different places. These are ones that have the highest clinical value and then with this knowledge, developing drugs that interfere with the ability of cancer cells to set shop anywhere or in as many places as possible to have the most effective drugs. The drugs with the widest spectrum of possible benefit.
Kat - And just to end really briefly, we’ve spent so many years, so many decades researching cancer. How close do you think we are to actually really making breakthroughs in treating a cancer that has spread?
Joan - I think we are already making great success because many cancers, 50% or more are cured. Metastasis however is the last bastion and is the most difficult segment of the disease and this is what a large community now has engaged itself in conquering. So, we are going to be seeing, I'm sure over the next years and decades, progressive resolution of this problem.