THE MOSS REPORTS

What is cancer? Is it one disease, or many? It may surprise you to know that scientists are far from clear on these most fundamental questions.

Last week I reported on a 2004 experiment at the University of Massachusetts Medical School (UMSS), showing that some stomach cancers are caused by microbes and actually originate in bone marrow derived stem cells (BMDCs). I conclude the article this week.

The model of cancer causation that emerges from this work could change our understanding of cancer on a fundamental level and has wide-ranging implications for the future of cancer research as a whole.

For thirty years I have been monitoring the field of cancer research and treatment, chronicling the advances and setbacks, the small triumphs and the many frustrations of the war on cancer.

The fruit of my long involvement in this field is The Moss Reports, a comprehensive library of more than two hundred individual reports on specific cancer diagnoses. For cancer patients, a Moss Report represents an invaluable guide and handbook for the journey ahead.

If you would like to order a Moss Report for yourself or someone you love, you can do so from our website, www.cancerdecisions.com, or by calling Diane at 1-800-980-1234 (814-238-3367 from outside the US).

We look forward to helping you.

A NEW VIEW OF CANCER'S ORIGINS – PART II

Unitarian Theory?

Conventional thinking states that cancer is a group of 200 or so different diseases, each of which has its own distinctive features and causes. In this widely accepted model, lung cancer arises from normal bodily (or somatic) cells of the lung, those of the liver from normal liver, and so forth.

In this UMMS experiment, however, Dr. Houghton and her colleagues clearly demonstrated that the cancer developing in the stomachs of the experimental animals - despite every appearance to the contrary - is not really stomach cancer at all. It is caused by the transformation of bone marrow-derived stem cells, which come rushing to the scene in order to help, but are then themselves overwhelmed.

Why then do they look so much like malignant stomach cancer cells that they could fool almost any pathologist who looked at them under the microscope? Probably because these cells develop within the distinctive hormonal "microenvironment" of the organ.

To repeat, these "stomach cancer" cells are masquerading, making themselves appear to be gastric in origin. But their true nature has now been unmasked: they are in reality stem cells that have been transformed under the influence of local infection and inflammation.

It may also turn out that other kinds of carcinoma come about in the same way. In fact, it is possible that this will develop into a model for cancer in general, and that in the future we will no longer be able to talk meaningfully about "stomach," "liver," "breast," or other kinds of carcinoma, but all cancers will be found to have a common origin.

Is cancer then many diseases or one disease with many manifestations? This is one of the oldest debates in oncology. There have been advocates of the single origin (or 'unitarian') theory of cancer, even in conventional medicine. My old boss at Memorial Sloan-Kettering, Lewis Thomas, MD, believed that cancer would eventually be proven to be a single disease. But for a long time, it has been the CAM movement that has provided a refuge for such single-etiology theories.

The classic example of a single, or unitarian, worldview is the trophoblastic theory of cancer. This was essentially propounded in 1902 by the Scottish embryologist John Beard, DSc, and then revived more than half a century ago by Ernst T. Krebs, Jr., and two colleagues. They proposed that all cancer was identical in nature, and that its origin was in generally distributed primordial 'diploid totipotent cells,' which are similar to what are now called stem cells.

Here is what Krebs wrote at mid-century:

"It is veritably impossible to find, among the hundreds of valid experimental contributions to our knowledge of cancer made during the past half century, an experimentally established datum that would controvert the thesis of the basic biological uniformity characterizing all exhibitions of cancer." (Krebs 1950)

This seemed overblown at the time, but more recent work on stem cells at the University of Michigan has shown that it is indeed stem cells, not ordinary somatic cells, that cause breast cancer in another experimental system. Only a tiny minority of cells in these human tumors (growing in immune-deficient mice) are capable of inducing new cancers; the rest are relatively harmless.

"These tumor-inducing cells have many of the properties of stem cells," said Michael F. Clarke, MD, the Michigan professor of internal medicine who directed a 2003 study. "They make copies of themselves - a process called self-renewal – and produce all the other kinds of cells in the original tumor." These really malignant cells have a unique configuration of surface markers: all express a protein marker called CD44, in addition to having either very low levels, or no levels, of another marker called CD24.

It will certainly be interesting to see if there is a relationship between Dr. Houghton's BMDCs and Dr. Clarke's malignant stem cells. One tell-tale sign would be the presence of these CD44+/CD24- cells. Another would be the expression of chorionic gonadotropin, the characteristic hormone of pregnancy.

These are truly exciting times for cancer research. Investigations of stem cells in many laboratories is homing in on their connection to the origin of cancer. If such modern discoveries could be combined with the rich history and practical experience of the CAM movement, this could lead to a scientifically valid theory of cancer.

Could a cure for cancer be far behind?

--Ralph W. Moss, Ph.D.

Anderson DJ, Gage FH, Weissman IL. Can stem cells cross lineage boundaries? Nat Med. 2001;7:393-5.

Balkwill F, Mantovani A. Inflammation and cancer: back to Virchow? Lancet. 2001;357:539-45.

Couzin J. Medicine. Tracing the steps of metastasis, cancer's menacing ballet. Science. 2003;299:1002-6.

Houghton J, Stoicov C, Nomura S, et al. Gastric cancer originating from bone marrow-derived cells. Science. 2004;306:1568-71.

Krebs, ET, Jr., Krebs ET, Beard HH. The unitarian or trophoblastic thesis of cancer. Medical Record 1950;163:149-174.

Normile D. Cell proliferation. Common control for cancer, stem cells. Science. 2002;298:1869.

UMMS Public Affairs. Bone marrow-derived stem cells linked to gastric cancers. New thinking on the source of gastric cancer. Nov, 25, 2004. Accessed Feb. 16, 2005. Available at:
http://www.umassmed.edu/pap/news/2004/11_25_04.cfm

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The news and other items in this newsletter are intended for informational purposes only. Nothing in this newsletter is intended to be a substitute for professional medical advice.

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