Monday, February 7, 2011

Parable of the soils

One of several things that Dr. C and I discussed at my appointment last week was what’s called the “seed and soil” hypothesis of cancer metastasis. Despite the steady appearance of mets in subcutaneous fat over the past year, they’ve so far not spread to other parts of my body. That’s a mercy, but it strikes me as odd: Why would cancer cells once disseminated throughout the body, as they surely have been, only manifest themselves in this particular tissue? This selectivity is not what you’d expect intuitively from cells with the wildly proliferative behavior of metastatic melanoma.

Sunset at Badwater in Death Valley
When I asked about this, Dr. C patiently explained that just as certain seeds like to grow in certain soils, so malignant melanoma has a propensity to seed in certain tissues. The first time he used this analogy last year I figured it was just a painfully elementary way of explaining some abstruse concept in cellular biology. It seems there’s more to it than that, which I will explain.

It was an English surgeon in the late 19th century named Stephen Paget who first identified the important role played by tissue microenvironments in the formation of metastases. The question he asked was, “What is it that decides what organs shall suffer a case of dissemination of cancer?” His search for answers to this conundrum led him to formulate the seed and soil concept, of which Dr. C provided a respectable reinterpretation. Paget’s insight into the natural history of cancer has stood the test of time, and his hypothesis has been supported and confirmed in recent decades.

The most common sites for metastases in melanoma are the lung, liver, brain, bone—and subcutaneous fat. Dr. C said about 15% to 20% of his patients with stage 4 melanoma present with sub-q’s. This layer of fat lies just under the skin layers and contains blood vessels that supply the skin with oxygen, and nerves. Subcutaneous fat serves as a shock absorber for the skin, and also stores energy that the body uses during periods of strenuous activity. When I’m doing long-distance running, especially marathons, my body draws energy from the same tissue that is now the “soil” in which my melanoma grows. I wish I could be told that if I were to run hard and far enough, I could burn up enough of this fat to starve the melanoma. Believe me, I’d give it a go. I remain convinced that simple, clean living is its own reward, but it’s no cure for cancer.

In an attempt to grasp at straws, I asked Dr. C if he thought I was doing anything right that might account for the melanoma not spreading beyond the skin. He gave a non-answer, which was what I expected. The affinity of my melanoma, with its unique set of genetic mutations, for the fat beneath my skin is inscrutable. It just is. The seeds and soil are a good match for reasons that I probably wouldn’t understand even if they could be explained.

One of the major obstacles to therapy for metastatic cancer of all types is the biologic heterogeneity of tumor cells. My melanoma is truly mine in the sense that the particular set of mutations that distinguish it are unlike anyone else’s. At this point I don’t know what any of those mutations are, but a small number of them are being targeted by drug developers. The best known among them is the so-called B-RAF mutation, which is shared by about half of all patients with stage 4 melanoma. The cancer cells of some melanoma patients have been found to have thousands of mutations. And these cells don’t ever stop mutating, which is just one reason why effective treatments are so elusive. I donated tissue to the tumor registry at OHSU last year, so it’s possible that Dr. C could discover if I have the B-RAF mutation with just a phone call. That knowledge doesn’t serve any immediate purpose, but it’s good to know it's likely available.

For many people, the seed and soil hypothesis brings to mind the parable of the soils that are recorded in the Gospels. As Jesus tells the story, the sower drops seed on the path, on rocky ground, and among the thorns, and none of it survives. Finally, he casts seed on good earth, where it grows and yields abundantly. The profligate growth of cancer in the “good soil” of subcutaneous fat is not good news medically , but as in all parables, there seems to be a lesson buried within it. I continue to puzzle over this and wonder if its meaning might yet be grasped.

1 comment:

Anonymous said...

Perhaps your lack of "soil" is restricting the spread of the cancer. So keep running and no moe CFS. Nice picture.