Monday, August 17, 2009

PRECANCERS: 2 Inducing regression in precancers

Precancers are the lesions from which cancers develop. Precancers can be easily treated, and when we eliminate precancers, we eliminate the cancers that would have developed from the precancers. This is the message of my new book, Precancer: The Beginning and the End of Cancer. In today's blog, I thought I'd provide one example, from the recent cancer research literature, of precancer treatment.

Colon cancer is one of the most common cancers of humans, accounting for about 50,000 deaths in the U.S. in 2009 (data from U.S. National Cancer Institute at:

Almost all colon cancers arise from colon precancers, called colonic adenomas.

If we could eliminate colon adenomas, we could eliminate virtually all deaths from colon cancer. This is the premise behind colonoscopy (excise the adenomas and avoid the cancers).

A team of scientists from MIT, Mass Genl, Harvard and several other institutions have published a recent article in PNAS (Proceedings of the National Academy of Sciences), on the successful treatment of colon precancers, in a mouse model system.

The article is:

Elias Gounaris, Susan E. Erdman, Clifford Restaino, et al. Mast cells are an essential hematopoietic component for polyp development Proc Natl Acad Sci U S A. 2007 December 11; 104(50): 19977-19982.

The full-text article is available as an open access document:

The investigators noticed that the stroma (the supporting connective tissue) in colon adenomas is infiltrated with mast cells (a blood cell involved in the inflammatory process). When the investigators reduced the mast cell population (in the tumor stroma) in precancerous mouse colon adenomas, many of the adenomas quickly regressed. In a related study, chimeric mice with a genetic deficiency of mast cell formation developed fewer colon adenomas than wild-type mice.

Precancers, unlike cancers, often regress spontaneously. It seems self-evident that it would be easier to treat a lesion that is unstable, and prone to die on its own, than to treat a lesion that has grown into a large, invasive mass, that has dissemminated throughout the body. This paper is one example of how easy it is to modify the growth of precancers and to induce a high rate of precancer regression.

Because treatment was aimed at the non-neoplastic cells in the stroma of the precancer, it is likely that the same treatment that was successful against colon adenomas may be successful against any precancer for which there is a population of mast cells that contribute to precancer progression. The authors discussed the observation that mast cells are found in a variety of human cancers, and, in a note attached to their paper, cited recent work indicating that mast cells have an important role in the development of pancreatic cancer and prostatic cancer.

It is important to begin treatment while neoplasms are stil in their precancer stage. AFTER an invasive cancer has emerged from a precancer, agents that target a sensitive step in precancer development will probably NOT be curative.

When we have candidate precancer treatments (and we do), we should start testing them in human clinical trials. When we learn how to eradicate precancers, we will have learned how to conquer cancer.

More on precancers in next post.

-© 2009 Jules J. Berman

related words: precancers, preneoplastic lesions, preneoplasia, ien, intra-epithelial neoplasia, intraepithelial neoplasia, intra-epithelial neoplasm, intraepithelial neoplasm, in situ carcinoma, carcinoma in situ, cis, dcis, din, pin, panin, cin, dysplasia, adenoma, preneoplastic, pre-cancer, pre-cancerous, precancerous
Science is not a collection of facts. Science is what facts teach us; what we can learn about our universe, and ourselves, by deductive thinking. From observations of the night sky, made without the aid of telescopes, we can deduce that the universe is expanding, that the universe is not infinitely old, and why black holes exist. Without resorting to experimentation or mathematical analysis, we can deduce that gravity is a curvature in space-time, that the particles that compose light have no mass, that there is a theoretical limit to the number of different elements in the universe, and that the earth is billions of years old. Likewise, simple observations on animals tell us much about the migration of continents, the evolutionary relationships among classes of animals, why the nuclei of cells contain our genetic material, why certain animals are long-lived, why the gestation period of humans is 9 months, and why some diseases are rare and other diseases are common. In “Armchair Science”, the reader is confronted with 129 scientific mysteries, in cosmology, particle physics, chemistry, biology, and medicine. Beginning with simple observations, step-by-step analyses guide the reader toward solutions that are sometimes startling, and always entertaining. “Armchair Science” is written for general readers who are curious about science, and who want to sharpen their deductive skills.