History of Cancer Treatments: Targeted Therapy

Until the late 1990s nearly all drugs used in cancer treatment (with the exception of hormone treatments) worked by killing cells that were in the process of replicating their DNA and dividing to form 2 new cells. These chemotherapy drugs also killed some normal cells but had a greater effect on cancer cells.

Targeted therapies work by influencing the processes that control growth, division, and spread of cancer cells, as well as the signals that cause cancer cells to die naturally (the way normal cells do when they are damaged or old). Targeted therapies work in several ways.

Growth signal inhibitors

Growth factors are hormone-like substances that help tell cells when to grow and divide. Their role in fetal growth and repair of injured tissue was first recognized in the 1960s. Later it was realized that abnormal forms of growth factors or abnormally high levels of growth factors contribute to the growth and spread of cancer cells. Researchers have also started to understand how cells recognize and respond to these factors, and how that can lead to signals inside the cells that cause the abnormal features found in cancer cells. Changes in these signal pathways have also been identified as a cause of the abnormal behavior of cancer cells.

During the 1980s, scientists found that many of the growth factors and other substances responsible for recognizing and responding to growth factors are actually products of oncogenes. Among the earliest targeted therapies that block growth signals are trastuzumab (Herceptin), gefitinib (Iressa), imatinib (Gleevec), and cetuximab (Erbitux). Many others are available today.

Angiogenesis inhibitors

Angiogenesis is the creation of new blood vessels. The term comes from 2 Greek words: angio, meaning “blood vessel,” and genesis, meaning “beginning.” Normally, this is a healthy process. New blood vessels, for instance, help the body heal wounds and repair damaged tissues. But in a person with cancer, this same process creates new, very small blood vessels that give a tumor its own blood supply and allow it to grow.

Anti-angiogenesis agents are types of targeted therapy that use drugs or other substances to stop tumors from making the new blood vessels they need to keep growing. This concept was first proposed by Judah Folkman in the early 1970s, but it wasn’t until 2004 that the first angiogenesis inhibitor, bevacizumab (Avastin), was approved. Currently used to treat advanced colorectal, kidney, and lung cancers, bevacizumab is being studied as treatment for many other types of cancer, too. And many new drugs that block angiogenesis have become available since 2004.

Apoptosis-inducing drugs

Apoptosis is a natural process through which cells with DNA too damaged to repair – such as cancer cells – can be forced to die. Many anti-cancer treatments (including radiation and chemo) cause cell changes that eventually lead to apoptosis. But targeted drugs in this group are different, because they are aimed specifically at the cell substances that control cell survival and death.

The future of targeted therapies

As more is learned about the molecular biology of cancer, researchers will have more targets for their new drugs. Along with more monoclonal antibodies and small signaling pathway inhibitors, researchers are developing new classes of molecules such as antisense oligodeoxynucleotides and small interfering RNA (siRNA). Research is being done to develop targeted drugs that are aimed at proteins produced by specific gene mutations in cancer cells, too.

Researchers are looking for gene mutations that cause some patients to respond better to certain drugs.