Cancer, while the second leading cause of death in the United States, is not just one disease. It's a condition in which cells break the most fundamental rules of behavior. For any number of reasons, cancer cells fail to repair damaged DNA, they reproduce without restraint, colonize other tissues in the body and ignore signals telling them to self-destruct. The causes and consequences of cancer differ from type to type, and from patient to patient. On a molecular level, rarely are any two cancers exactly the same.

Sanford-Burnham research on cancer

The cells shown here are dividing normally. In cancer, tumors form when cells continue to divide unchecked.

Scientists in each of the Sanford-Burnham Cancer Center’s four programs – Tumor Development, Signal Transduction, Tumor Microenvironment and Apoptosis and Cell Death Research – are interested in the most fundamental questions about cancer: How do tumors arise from normal cells? What happens to cellular communication as cancer develops? How do cancer cells interact with their neighboring tissues? How do cancer cells avoid cell death? Researchers hope to apply the answers to these questions toward the development of targeted technologies that deliver anti-cancer drugs specifically to the tumor – thereby avoiding side-effects – and therapeutics to trick cancer cells into committing suicide by restoring a natural cell death mechanism.

Below are just a few examples of Sanford-Burnham’s multi-pronged approach to understanding and combating cancer at each step in the progression of the disease:

Step 1: Something goes wrong in a cell

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Cancer stem cells are a hot area of focus in the Cancer Center’s Tumor Development Program. Much like other types of stem cells, cancer stem cells can give rise to a variety of cell types. Scientists at Sanford-Burnham and elsewhere are beginning to think that many cancers are caused by a small population of ‘initiator’ stem cells in adult tissue, which gives rise to all other cells in the tumor. This notion has led to the belief that while many traditional treatments (such as chemotherapy or radiation therapy) destroy the majority of the tumor cells, it only takes a few remaining cancer stem cells to re-initiate the tumor. Luckily, these cancer stem cells have certain molecular characteristics that make them distinguishable from other cells.

Researchers in the Tumor Development Program are now finding ways to distinguish cancer stem cells from other tumor cells and are using this information to design treatments that specifically kill them without harming other tissues. One Sanford-Burnham laboratory has discovered that breast cancer stem cells in mice can be forced to differentiate – producing functioning skin and milk-producing cells and halting tumor growth. This unique approach, called ‘differentiation therapy’, provides an alternative to directly killing cancer cells.

To read more, see: Genes and Cancer: Tumor Development

Step 2: Cancer cell growth spins out of control

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Cancer is rarely detected in its early stages. Cancer cells eventually become a large tumor mass, often because cellular signals that are supposed to regulate growth don’t work properly. Cells are supposed to receive information from their surroundings through receptors on the cell surface. The signal then passes inside the cells, triggering events that control and regulate cell growth. Cancer cells, however, ignore these environmental signals and keep growing, even while the body tries to control the growth. Sanford-Burnham’s Signal Transduction Program studies how these regulatory mechanisms go wrong in cancer. Here, two groups are studying EphA2, a cell signaling receptor found on the surface of cancer cells but not in most normal cells. In one approach, researchers are now working with pharmaceutical companies to look for drugs that inhibit EphA2, which is an enzyme that affects cellular function by adding phosphate groups to other proteins. In another approach, they are also using the knowledge that EphA2 is only expressed in cancer cells to team up cell-destroying drugs with molecules that specifically bind to the receptor, killing cancer cells while leaving normal cells untouched.

To read more, see: Communications Breakdown: Signal Transduction

Step 3: Tumors metastasize

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In aggressive forms of cancer, tumors are no longer isolated clusters of cells. Rather, they direct the creation of new blood vessels that bring fresh oxygen and nutrients to the growing mass – a process known as angiogenesis. These new roadways also connect the tumor to the body’s circulatory system, providing cancer cells with a means of escape. In Sanford-Burnham’s Tumor Microenvironment Program, scientists are trying to determine what mechanisms allow some cancer cells to metastasize. Scientists are looking for ways to choke off the blood supply and block their escape. What’s more, some researchers at Sanford-Burnham are also targeting cells that have already left the nest. One group is developing short proteins called CendR that specifically home in on both cancer cells and the blood vessels that feed them. CendR and similar technologies are being coupled with known anti-cancer drugs, such as Herceptin® (currently prescribed to treat certain kinds of metastatic breast cancer), to dramatically increase their potency and minimize side effects.

To read more, see: Rebuilding Cancer’s Neighborhood: Tumor Microenvironment

Step 4: Cancer cells refuse to die

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Regardless of how well anti-cancer drugs work at the beginning, there are almost always some cancers that manage to keep coming back. Cancer cells can learn to resist death imposed by radiation, chemotherapy or other drugs by changing their genes or altering expression of proteins on the cell surface. But the main reason some cells are able to resist treatment is because they can prevent activation of the programmed cell death pathway, called apoptosis. Most cancer drugs work by inducing stress in the cell, which results in molecules leaking out of the mitochondria (the part of the cell that generates energy) and activating enzymes known as caspases. Activation of caspases leads to irreversible cell damage and apoptosis. Since cancer cells survive by activating caspase inhibitors called IAP proteins, Sanford-Burnham scientists in the Apoptosis and Cell Death Research Program are trying to trick cancer cells into committing suicide by taking IAPs away and allowing apoptosis to proceed.

Some groups are also tackling Bcl-2 proteins, a family of mitochondrial proteins that antagonize one another to drive either cellular survival or death. Cancer cells have more pro-survival Bcl-2 proteins than normal cells do. Sanford-Burnham scientists have already developed drugs that shift the balance of pro-death and pro-survival Bcl-2 members to wipe out cancer cells and are continuing to improve them.

To read more, see: Unlocking the Secrets of Cell Death: Apoptosis and Cell Death Research

For more information

Sanford-Burnham does not provide clinical care for cancer or for other diseases. However, there are many organizations that do, nationwide and in California and Florida. If you are looking for a medical doctor or clinical trial, please visit this list.

National Cancer Institute (NCI), part of the National Institutes of Health (NIH)
http://www.cancer.gov/

American Cancer Society
http://www.cancer.org/

American Association for Cancer Research
http://www.aacr.org/

Susan G. Komen for the Cure
http://ww5.komen.org/

Stand Up To Cancer
http://su2c.standup2cancer.org/

Research - Cancer - Your Health: SBMRI's Work
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Genes and Cancer: Tumor Development
Communications Breakdown: Signal Transduction
Rebuilding Cancer’s Neighborhood: Tumor Microenvironment
Unlocking the Secrets of Cell Death: Apoptosis and Cell Death Research
Breast Cancer