A More Precise Aim at Cancer

In the 4 decades since the US declared the war on cancer there have been just a few notable discoveries. A new type of therapy that targets one tiny aspect of a cancer cell’s life is taking aim to save the lives of many.

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Ever since the National Cancer Act became law in 1971, the United States has made the war on cancer a priority. We now know that there are many different reasons why some cells grow uncontrollably and take the lives of more than 1500 Americans every day. In the decades since, there have been a few standing ovations. But a new type of treatment is already causing a shift in how doctors treat cancer.

Much of how we look at cancer treatment today has to do with advancements in molecular biology, a branch of science that looks deep within a cell's inner workings. For one thing, technology has become more sophisticated allowing scientists to map a cell's DNA. When DNA gets damaged, the recipes for chemical signals can get sabotaged and that can make cells misbehave, grow out of control and edge out healthy cells.

Honing in on the unique molecular aspects of cancer cells is at the heart of an amazing new concept in cancer treatment, "targeted therapy". And a growing number of cancer specialists believe that this approach is the future of cancer treatment.

 

Taking Aim

Targeted therapies are different from traditional cancer therapies. Chemotherapy kills all rapidly dividing cells, healthy or not. The drugs coarse through the blood stream and kill cells that are actively growing and dividing, a hallmark feature of cancer cells, but also one of some healthy cells too. That is why people who receive chemotherapy experience side effects such as hair loss, nausea and gastrointestinal symptoms because the cells of these systems are constantly turning over and dividing making them susceptible to chemotherapy.

Radiotherapy, while a little more precise, also inadvertently kills healthy cells. And even though the radioactive beam is sighted directly above the tumor cells, the beam doesn’t distinguish healthy cells from cancerous ones.

Targeted therapies however are very specific about where they go. They are designed to zero in on a potentially vulnerable aspect of a cancer cell's life. Researchers study features of cancer cells that either don't exist in a healthy cell or are particularly unique to a specific cancer.

Targeted drug therapy can block proteins, enzymes and receptors that fuel cell growth. They can modify mechanisms that turn cell growth on and off, or cause cancer cells to wither away.  Still other targets mimic the body's own immune system as antibodies that recognize and kill something that doesn't belong.

Molecular Targets

The first molecular target was found on the surface of certain breast cancer cells. A region on the cell's membrane had a particular affinity for estrogen. Estrogen can fuel the growth of some types of breast cancer but when the receptor was blocked, the cells were less likely to grow out of control. Several drugs have been specifically designed to hook into the estrogen receptor's spot, leaving estrogen out of the lurch.

Another well-known molecular target was developed for chronic myeloid leukemia (CML), a rare blood cancer. It was the first cancer to have a drug target intentionally designed to pull the plug on a cancer-fueling enzyme that has great growth-signaling powers. CML is a type of blood cancer caused by too many inefficient white blood cells in the bone marrow and blood, a potentially fatal scenario. But these badly behaving white blood cells have some unique molecular characteristics, making them ideal for targeted therapy.

Somehow, on CML-causing white blood cells, a region on chromosome 22 swaps with a region on chromosome 9, and this new arrangement produces the abnormal chromosome called the Philadelphia chromosome (named for the city where the discoverers lived). This abnormality is the key to the disease. Unfortunately the mutated Philadelphia chromosome makes an enzyme that keeps a cell’s divide signal in the "always on" position. And when the cells containing the Philadelphia chromosome flourish, they crowd out healthy cells, and the incompetent white blood cells grow unchecked.

Since almost all people with CML are Philadelphia positive (Ph+), Dr. Brian Druker, an oncologist at Oregon Health and Sciences University, proposed developing a drug to disable this enzyme. As a result many people with Ph+ CML, who once had few good treatment options, now have a chance at a disease-free life.

Monoclonal Antibodies

Antibodies can also be designed to become targeted therapies by recruiting them to do what they do best; zero in on a specific protein in or on a cell’s surface and mount an attack. If a cancer protein unique to a type of cancer is identified, an antibody can be designed to attack it. Then an exact copy or clone of that antibody can be engineered in a lab to match it (hence the name monoclonal antibody).

Some monoclonal antibodies targets carry a toxic payload along for the ride – a chemical or radioactive agent to increase the power of the attack. This is sometimes called immunotherapy, or radiotherapy if a radioactive agent is attached.

Patients with non-Hodgkin's lymphoma received the first monoclonal antibody developed to treat cancer and targets are either available or in development for almost all types of cancer.

For more information

National Cancer Institute Targeted Therapy Factsheet