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Targeted Therapies in Cancer Care

By David Grossman, MD, Hematologist/Oncologist
The Chester County Hospital

Published: October 6, 2008

Since the beginning of medical treatment, the care of patients with cancer has depended on three cornerstone therapies. In the early days, radical surgery was the only modality of therapy available. This led to the line of thinking that aggressive surgery was the best way to treat patients with cancer. Radiation therapy was introduced in the early part of the 20th century, and in the 1940s, the first modern linear accelerator was developed adding another modality to cancer therapies. Finally, the introduction of chemotherapy made a systemic, as opposed to local, therapy available to treat disease in a variety of places simultaneously. The mark of all of these therapies was the need to destroy normal tissue along with the malignant cells in order to prolong the life of a patient or to cure them. Through the 1970s, more treatment and aggressive surgery were felt to be more likely to cure patients.

In the mid-to-late 1970s, there was a movement to look at the extent of surgery for women with breast cancer and this marked the advent of attempts at less radical surgery with combined radiation/chemotherapy as a multimodality therapy to reduce the morbidity (damage) from therapy and maintain effectiveness/cure rates. This approach has been echoed in Hodgkin's Disease and Germ Cell Cancers as these patients are frequently cured and live long enough to suffer the long-term side effects of treatment including leukemia, second malignancies, premature heart disease, etc. The goal of therapy changed to find the least amount of treatment needed to maintain the effectiveness of therapy at the same time trying to limit the damage to normal tissue.

In the mid-1990s, an antibody was developed against the HER2/neu receptor on breast cancer cells. Herceptin directly targets this growth receptor and leads to prolonged life in patients whose disease spread outside the primary cancer, and increased cure for women with localized disease. It has a low toxicity profile compared to chemotherapy.

In the late 1990s, a compound was discovered that changed how Oncologists viewed the treatment of cancer. Chronic Myelogenous Leukemia (CML) had long been known to have a characteristic chromosome mutation (or oncogene) known as the Philadelphia Chromosome. (Named as such since it was discovered in the lab of Dr. Peter Nowell at the famed Wistar Institute of the University of Pennsylvania in the 1960s.) When the product of the Philadelphia Chromosome was found to be the promoter of the malignant change in the leukemia cells, the search was on for an agent to block that function. This was the beginning of "rational drug development" where the target was known and the blocking agent was sought. Discovered in the late 1990s, Gleevec immediately leapt to the forefront of the line of therapies for CML. This was a disease that had been uniformly fatal in a median of two years for any patient over the age of 40 who could not have bone marrow transplantation. The life-prolonging therapies needed before Gleevec included drugs that required injections several times weekly and made patients feel terrible. Gleevec is a pill taken once daily with relatively few side effects, that is a curative therapy in the vast majority of patients. There is no overstating the impact that Gleevec has had on the practice of Oncology, being the forerunner of change in how we search for new therapies to treat cancer.

In addition to Gleevec, we now have several drugs that bind to and inhibit a key growth factor in a variety of cancers called the epidermal growth factor and its receptor. We also have drugs that target the cancer cell's ability to make new blood vessels needed for survival and spread. More therapies are in the pipeline. The hallmark of all of these new therapies is a targeting of a specific process in the malignant cell that is generally unique to that malignancy and not present on normal cells.

So-called "targeted therapy" has the potential to change the face of cancer treatment in the years to come. There is now the potential, in our lifetime, for us to be able to look back on how cancer was treated before the new millennium and shake our heads in disbelief that we had to do it that way, just as today we look at the pre-antibiotic and pre-anesthesia days of long ago.

This article was published as part of the Daily Local News Medical Column series which appears every Monday. It has been reprinted by permission of the Daily Local News.

Last Updated: 7/27/2009