How cancer cells often send the wrong signals

The human body functions in large part due to the billions of chemical signals sent between and within cells. Healthy cells exchange signals to regulate the immune system, help muscles and organs function, and perform an endless list of biological tasks. These signals also determine how cells grow and divide, and when they shut down to make room for new, healthy cells (called apoptosis)—critical processes that determine everything from how the body heals injured knee to how the skin ages and how the brain develops and processes pain.

This constant communication is so critical to the health and development of the body that when cellular signals fail, interference can cause a number of conditions or diseases, such as diabetes or cancer. In fact, researchers have concluded that many cancers form when these signals are interrupted, diverted, or put to other, more harmful uses. This cutting-edge knowledge has become a major focus of research that has led to a new and emerging line of cancer treatments.

As scientists learn more about how cellular signals work and what happens when they mix, they are discovering that intercepting signals from broken cancer cells can help the body fight disease. Some drugs, for example, are designed to block the signals that cancer cells send to evade the immune system. In other cases, cancer cell signaling remains a mystery and a powerful focus of future research. “We have a lot to learn about the intricacies of cell signaling, the avoidance of apoptosis, and other mechanisms of cell growth and regulation,” says Dr. Pamela Creeley, MD, director of the Division of Medical Oncology at Cancer Treatment Centers of America. ^® (CTCA) and chief of the medical oncology department at our Philadelphia Hospital. “At the same time, there have been important advances in the fields of biology, oncology and immunology that can translate scientific findings into treatments.”

Receive the message

The cell receives messages through receptors on its surface. Receptors are like equivalent cellular antennas that receive chemical signals through protein molecules, or ligands, from other cells. When the bond reaches the receptor, it sets off a chain reaction that allows the signal to penetrate the cell surface and reach the thick fluid inside, called the cytoplasm. Once inside the cell, the message is passed from one enzyme to another along the signaling pathway until it reaches its destination: the nucleus, where each cell’s DNA is located. The cell then executes the instructions encoded in the signal.

On any given day, the cells of the body send and receive billions of signals. In some cancer cells, the signals sent to regulate growth or initiate apoptosis are short-circuited, resulting in rapid cell growth that can lead to tumors. For example, the human epidermal growth factor receptor 2 (HER2), which is found on the surface of normal cells, sends signals that help the cells grow. In some breast cancer patients, the cells produce too many HER2 receptors, causing an overload of signals that can lead to uncontrolled growth.

Bypass the main signal

While healthy cells continue to divide and thrive, cancer cells can take control of these signaling pathways and use them in harmful ways, for example, to help them grow and spread. One of the oldest and most important signaling pathways in the body is called the hedgehog. More active before birth and during childhood, the hedgehog’s pathway conveys a variety of instructions that tell the body how to develop and maintain our organs, skin, and bones. As we enter adulthood, the Hedgehog pathway is nearly shut down, unless cancer cells activate it again. Once activated, the signaling pathway that used to help the body mature as we got older can now be used to help the spread of tumors. California scientists have linked reactivation of the Hedgehog pathway to gastrointestinal stromal tumors, while North Carolina researchers conclude that one signal that reactivates the pathway “

Scientists believe that if cellular communication is key to helping some tumors develop, it can also be used to reverse behavior and, in some cases, kill cancer. The development of drugs designed for a specific receptor, ligand, or pathway is the basis of some targeted therapies, which are used to treat different types of cancer. These drugs are designed to disrupt cellular communication by:

• Target the ligand so that it cannot connect to the future. For example, bevacizumab (Avastin®), used to treat non-small colorectal, breast, kidney, and lung cancers, as well as some brain tumors, attempts to block a specific protein from binding to a receptor that triggers growth signals, aborting the communication that helps cancer grow and thrive.
• Go to the receiver. Trastuzumab (Herceptin®), for example, one of the most commonly prescribed drugs for HER2-positive breast cancer, is designed to target defective HER2 protein receptors and block growth signals.
• Targeting the signaling pathway within the cell. When the receptor is activated, it releases an enzyme known as tyrosine kinase, which acts as an on and off switch for many cellular signals. Tyrosine kinase inhibitors such as erlotinib (Tarceva®), which is used to treat some non-small cell lung cancers and pancreatic cancers, are designed to keep this switch off.

The hope, Dr. Creeley says, is that finding new ways to harness those connections and learn more about the intricacies of signaling pathways will help cancer researchers develop new cancer treatments. “Researching the details of signaling pathways could provide scientists with insights into new drug treatments that could have a significant impact,” he says.

In the search for better treatments and prevention strategies, scientists are learning more about how cancer grows and survives, even in the harshest environments. This blog is part of an occasional series called How Does Cancer Do It? Designed to highlight recently discovered cancer-related behaviors that add to our growing understanding.