The big C

Film producer Laura Ziskin died yesterday of breast cancer. She’s known for the Spider Man movies and Pretty Woman, and a lot of other films besides. Driving home today, I heard her obituary on NPR, and one bit in particular caught my ear. Ms. Ziskin was speaking before an audience, telling them she was “hopping mad about the state of cancer research,” and that 1500 Americans will die every day of the disease.

I sympathize with her. This woman lost her life to breast cancer and she saw it coming and she was pissed. I would be too. Like everyone else here (I imagine), my life has been shaped by the cancers of those close to me, and I dread it as much as anyone. But her “hopping mad” comment implies an understanding which I think is faulty to the core, and I feel compelled to set the thing right, because getting mad is not going to solve the problem. Nor will throwing more money at cancer research (though I doubt that would hurt).

Back when I taught residents and med students, I used to give a talk about cancer that had one purpose only: to impress upon my audience the hugeness of the problem. I’d like to see if I can do the same thing here, in relatively few words, with what I assume is a medically unsophisticated audience (for the most part). Here goes. Follow my logic . . .

1. Cancer is uncontrolled growth: your own cells gone renegade, growing too fast and going places in the body they have no business going, ultimately compromising the function of nearby organs.

2. With respect to cancer, two types of genes regulate cell growth: tumor suppressor genes and oncogenes. Tumor suppressor genes help to down-regulate growth while oncogenes tend to promote uncontrolled growth. If a tumor suppressor gene is destroyed by mutation, the cell harboring that gene has one less check on its growth potential. Yes, the distinction between oncogenes and tumor suppressor genes is a bit artificial. Used to be very clear to me back in the 80s, but as time goes on, I find the dividing line to be less and less clear.

3. Cancers generally form as the end result of a multistep (multi-mutation) process. How a particular cancer behaves (whether this person’s cancer will respond to radiation or chemotherapy, for example) depends on that tumor’s mutation history. If we assign letters of the alphabet to particular oncogenes or tumor suppressor gene mutations, then a ZJVAST cancer might behave very differently than a ZJVASL cancer. Capisce?

4. And so we come to problem #1: there is no single disease “cancer.” Any organ you might name can play host to a range of cancers, some rotten, some evil incarnate. If I learned tomorrow that I had papillary carcinoma of the thyroid, I wouldn’t be happy about it, but I wouldn’t let the news devastate me. If I learned instead that the cancer were an anaplastic carcinoma of the thyroid, I would write my will. Quickly.

Breast cancer is not lung cancer is not brain cancer is not intestinal cancer. Each organ system has its various subtypes of cancers. Each subtype of cancer can be further broken down into whether a particular gene or genes is involved in the pathway leading to cancer.

To give one concrete example: squamous cell carcinoma of the oral cavity has a very different behavior if it is a smoking-related cancer rather than a papillomavirus-related cancer (the latter being the more treatable, and more survivable, of the two).

5. The same type of cancer — oh, let’s pick on another baddy, squamous cell carcinoma of the esophagus — may be very different from one patient to the next. The two cancers will likely have different mutation histories, but it’s worse than that: the two patients have different genomes, too. Host factors, that’s the term we use. And one should never underestimate the importance of host factors.

Thus problem #2: not only is there no single disease “cancer,” the same named cancer is very different from one patient to the next.

And it gets worse.

6. Problem #3: cancer cells are genetically unstable, usually as a result of the mutations which led to their development in the first place. In a population of cancer cells, not all of the cells are identical. They’re not little clones of one another. They are quite literally a population of diverse individuals. You will readily appreciate problem #4: this population evolves (changes) over time, due to this same instability.

What’s bad about a changing population? Try making the whole damn thing go extinct. It’s tough*.

So unlike Ms. Ziskin, I’m not hopping mad about the problem. Despairing is probably a better word to describe how I feel. I’m amazed we do as well as we do in treating cancer patients — and I give a lot of credit to those “host factors” that I mentioned above but gave little attention to (the immune system is only one small part of the story, FYI).

As of 2011, the vast bulk of cancer therapeutic research is aimed at developing and testing particular treatments for particular cancers. That’s the research that will have the fastest impact on today’s cancer patients. I would like to argue, though, that the better approach — or at least, an approach we neglect at our peril — would be to put more effort into basic research. Not just cancer research, or biological research. All basic research. Because who knows when some materials scientist or nanotechnologist might chance upon the Next Big Thing that lets us throw our current treatments out the window, because it’s just that good?

D.

*But hey, we humans are clever that way! We make populations go extinct all the time.