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Targeted Therapies

The Future of Cancer Care

by Jeff Boyd, PhD

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Today, breast cancer, colon cancer, ovarian cancer, and brain cancer all receive the same standardized therapies, despite the fact that no two tumors, even from the same organ, are truly alike. But this “one size fits all” approach to treatment is about to change.

We are now at an inflection point in cancer medicine. Increasingly over the coming years, genetic profiles of an individual’s tumor will guide targeted therapies that will be both safer and more effective than currently available treatments. In fact, a handful of these new therapies are already available and proving the importance of this new approach to treating cancer.

Cytotoxic Therapies – The Mainstay of Cancer Treatment
The first use of chemotherapy to treat cancer in an adult was accomplished in 1960 using a drug called methotrexate against a tumor of the placenta. Despite initial resistance by the cancer research establishment to what was then considered a radical approach to cancer treatment, the use of cytotoxic chemicals – agents that kill cells – has become the mainstay of cancer therapy over the past 50 years. Many cancers are also treated with cytotoxic radiation therapy, often combined with chemotherapy, to achieve the most effective cancer control.

Rather than just one disease, cancer is an extraordinarily complex set of genetic diseases.

Author of Article photo

Dr. Jeff Boyd

Uncontrolled cell division is the hallmark of cancer, and chemotherapy and radiation are designed to interfere with the cancer cell’s ability to divide. Current treatment strategies for nearly all cancers, except early-stage tumors that may be cured by surgery alone, involve the use of cellular poisons – chemicals, radiation, or both – that act indiscriminately on dividing cells. By causing DNA damage, these agents induce cancer cells to undergo a “programmed” death, or simply cease to divide. The untoward side effects of many cancer treatments (for example, hair loss and gastrointestinal distress) occur because the treatments affect most of the dividing cells in the body, not just the cancer cells.

Targeted Therapy – A New Revolution in Cancer Care
Rather than just one disease, cancer is an extraordinarily complex set of genetic diseases. It takes multiple, acquired genetic alterations to convert a normal cell into a tumor cell, and these changes differ between and among tumor types. There are approximately 22,000 genes in the human genome, all of which are subject to mutation or altered expression levels. Amazingly, thousands of genetic mutations may be involved in the development of a specific cancer. The key to successful cancer treatment is to identify these mutations and understand which are most amenable to therapy.

The revolution leading to the possibility of targeted therapy as a mainstay of cancer treatment has been made possible by major advances in two areas: information and technology. Information has come from the deciphering of the human genome. By determining the exact sequence of all 3.3 billion base pairs of DNA that encode the 22,000 genes in our 23 pairs of chromosomes, it has become theoretically possible to determine every genetic change that has occurred in the transformation of a normal cell into a cancer cell. This is due to technological advances that allow DNA sequencing machines to determine the genetic architecture of an individual cancer.

In order to avoid killing healthy cells along with the cancer cells, we must figure out which genetic alterations and molecular aberrations are present in a specific tumor, and which of these may be susceptible to a particular therapy. Targeted therapeutic agents take aim at a specific genetic or molecular defect known to exist in a given tumor. Typically, these agents are composed of synthetic molecules or natural antibodies that do not have wide-ranging toxic effects on normal cells. They attack the “Achilles’ heel” of the tumor, generating a specific response to the therapy.

Well-established examples include the drug trastuzumab (Herceptin®), which targets an overexpressed gene present in some breast cancers, and imatinib (Gleevec®), which targets an abnormally altered gene in chronic myelogenous leukemia. These therapeutic agents have produced impressive clinical responses with relatively few side effects, compared to standard therapies for these cancers.

Looking to the Future
In the future, cancers will be classified and treated based on their genetic and molecular makeup rather than where they originate in the body. This targeted approach to cancer therapy will result in less toxicity, fewer side effects, and most importantly, more durable remissions for advanced cancers of many types.

While curing cancer is obviously still the long-term goal of the biomedical research community, it is entirely reasonable to expect that in the near future, transforming advanced cancer into a chronic, rather than fatal, disease is possible for many tumor types. It is safe to say that targeted therapy is the most important and promising breakthrough in cancer treatment in the past 50 years.

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Dr. Jeff Boyd is the senior vice president of Molecular Medicine and the executive director of the Cancer Genome Institute at Fox Chase Cancer Center in Philadelphia, PA.

This article was published in Coping® with Cancer magazine, November/December 2011.