FEATURE ARTICLE
Fighting Cancer Through the Study of Sarcomas
Although rare, cancers of the muscle, bone or fat carry the same molecular errors as other tumors, making them ideal subjects for the discovery of new therapies
Igor Matushansky, Robert Maki
Divide and Conquer
In the United States in 2005, almost two and a half million people will be diagnosed with some form of cancer, and about 570,000 people are expected to die of this disease. Indeed, cancer passed heart disease this year as the top killer of people under age 85. Although these survival statistics would be even grimmer without modern medicine, the best efforts remain inadequate.
The three pillars of treatment for cancer are surgery, radiation and chemotherapy. Of these three, chemotherapy is the least discriminating. Whereas surgical excision and radiation therapy are site-specific, standard chemotherapy kills dividing cells everywhere in the body. The rationale for administering such poison is that the cells that split frequently—usually cancer cells—should suffer the most. Although the strategy works well in some instances, say for treating leukemias, other types of cancer do not grow rapidly and are resistant to chemotherapy. Furthermore, normal cells that divide often—those in hair follicles and the lining of the gut, for example—are destroyed too, causing hair loss and diarrhea. Additional medications can alleviate some of these side effects but do not solve the fundamental problem, which is a lack of specificity.
Although new therapies based on advances in molecular biology have begun to enter clinical practice, the "holy grail" of oncology—a treatment that is both effective and completely specific to cancer cells—remains unknown. In fact, a single cure now seems more elusive than ever as physicians continue to learn about the many physiological changes that distinguish different forms of cancer from one another and from normal cells.
This heterogeneity among cancers is reflected in a relatively rare, highly diverse class of tumors called sarcomas. Thus, sarcomas are good (and popular) subjects for the study of therapies that physicians can use on other types of malignancies: More than a dozen medical centers and hospitals around the country specialize in sarcoma research and treatment.
The word "σαρκωμα"appears in the writings of the physician-philosopher Galen, who lived during the latter part of the second century A.D. In its original Greek, the term sarcoma describes a fleshy growth. Doctors use the word today to describe cancers derived from connective tissues such as bone, muscle, fat or cartilage. Each year in the United States, clinicians diagnose approximately 10,000 new sarcoma cases, encompassing 50 different types of cancer, each with its own distinctive biology.
Because relatively few people are afflicted with each sarcoma subtype, the disease doesn't lend itself to studies that require many patients, such as large-scale searches for susceptibility genes or big, randomized trials. Instead, most investigators look at pathological mechanisms using small-scale studies that are carried out on the cellular level. Consequently, scientists now know more about how sarcomas work than their scarcity might suggest, and clinical trials for sarcoma treatments are likely to reflect specific molecular data from experiments in a laboratory.
Our own research at Memorial Sloan-Kettering Cancer Center in New York strives to understand how sarcomas arise and to exploit that knowledge in the development of new treatments. Our work and the work of our fellow physician-scientists has led to several therapies for individual sarcomas, some of which are also proving useful in the fight against common types of tumors, such as those found in some lung cancers. This review highlights some of these advances.
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