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How Solid Tumors Differ from One Another

Solid tumors are the tumors that usually come to mind when someone hears the word cancer. They arise in tissues other than the blood-related tissues. Solid tumors also have gene changes, but they tend to be different and more extensive than those seen in leukemias and lymphomas. For example, while leukemia can sometimes result from a single cytogenetic abnormality like the 9;22 translocation, the development of solid tumors usually involves a smorgasbord of genetic changes. These include the activation of one or more oncogenes together with the inactivation of one or more tumor suppressor genes.

Oncogenes are normal genes that are involved in regulating cell division. These normal genes become oncogenes when mutations cause the genes to run when they shouldn't be or run faster than they should.

Tumor suppressor genes are genes that block or prevent inappropriate cell division. This can include the drastic step of triggering the cell to self-destruct when the cell's DNA is badly damaged by mutations. This process of self-destruction is known as programmed cell death, or apoptosis. When mutations disable tumor suppressor genes themselves, these safeguards are lost, enabling a cell to divide when it shouldn't or live longer than it should. Both are important characteristics of cancer cells.




A third group of genes that play an important role in cancer are those that produce DNA repair enzymes. DNA repair enzymes cut out and replace sections of DNA—of a gene—damaged by cancer-causing chemicals, oxygen radicals, or ultraviolet light (in skin cells), or that were duplicated improperly prior to cell division. When mutations disable these genes, damaged DNA isn't repaired as effectively, allowing mutations to accumulate more quickly.

Mutations occur daily in cells for a variety of reasons, and the laws of statistics tell us that eventually some will occur that are cancer-related. If repair enzymes are not working, that damage won't get corrected, and we're off to the races. (Some people are born with faulty genes for DNA repair enzymes, resulting in a higher incidence of certain cancers in these individuals. This is the basis for some hereditary cancers.)

Once a mutation occurs in a cell, it not only weakens the cell's ability to control its growth, but it allows other damage to follow more easily. One hit makes the cell sensitive to subsequent hits. That's why one cell progresses to cancer while the other ones around it don't.

Solid tumors arise because mutations in oncogenes, tumor suppressor genes, and genes for DNA repair enzymes accumulate over time, often a decade or more. By the time the cell becomes malignant, the cytogenetics are bizarre. Instead of something like a single 8;21 translocation that we can see in a fraction of leukemia cases that we know will be sensitive to standard therapy, solid-tumor cells may undergo a multitude of cytogenetic or genetic changes, some of which may resist almost any standard therapy.

That may be why some solid tumors are especially difficult to treat. The likelihood of any one treatment being effective for tumors with such a host of diverse genetic changes is probably not very high. More research in human cancer genetics should help us better sort things out at the genetic level, and will likely improve treatments and ultimately survival.

Some solid tumors stand apart from others in still another way: some tumors of the breast, uterus, and prostate grow faster in the presence of certain hormones. Hormone-dependent prostate tumors are sensitive to male hormones known as androgens; hormone-dependent breast tumors are sensitive to the hormone estrogen; and hormone-dependent uterine tumors are sensitive to estrogens and progestrone.

The growth of hormone-dependent breast-cancer cells is stimulated by the interaction of estrogen with molecules called estrogen receptors, which are found in the nucleus of those cells. When estrogen is added to a culture of breast tumor cells that have estrogen receptors, the cells grow; when the same cells are cultured without estrogen, they may almost stop growing.

Some breast tumors are composed of cells that lack estrogen receptors. Such hormone-independent breast tumors tend to grow faster than hormone-dependent tumors even in the presence of estrogen. When grown in the laboratory, hormone-dependent breast cancer cells double in number over several days. Hormone-independent cells, on the other hand, double in number in a day or two (for comparison, some lung or liver cancer cell have doubling times of 6 or 10 hours).

The presence of estrogen receptors in tumor cells provides an important therapeutic target. We can use the drug tamoxifen to block the receptors so that estrogen cannot bind to them and slow the growth of the tumor. Consequently, breast tumors are now routinely tested to determine if estrogen receptors are present (the tumor is then said to be ER positive) or absent (ER negative).

Hormone-dependent tumor cells are thought to retain some aspects of hormonal growth regulation seen in healthy breast cells. It may be that with the passage of time, mutations in ER-positive tumors cause the malignant cells to lose their sensitivity to estrogen and become hormone independent. This may represent a later stage in the progression of these malignancies.

This article originally appeared in Frontiers (Autumn 1998) a chronicle of cancer programs at The Ohio State University and was adapted for use on NetWellness with permission, 2004.

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Last Reviewed: Feb 21, 2005

Darrell E Ward, MS Darrell E Ward, MS
Associate Director
Cancer Communications
Wexner Medical Center
The Ohio State University

Robert W Brueggemeier, PhD Robert W Brueggemeier, PhD
Dean/Professor, Pharmacy Central Business Office
College of Pharmacy
The Ohio State University

Michael A Caligiuri, MD Michael A Caligiuri, MD
Professor of Hematology
Professor of Molecular Virology, Immunology, & Medical Genetics
College of Medicine
The Ohio State University

Reinhard A Gahbauer, MD Reinhard A Gahbauer, MD
Former Professor
The James
The Ohio State University

Eric H Kraut, MD Eric H Kraut, MD
Professor of Hematology
College of Medicine
The Ohio State University