New Hope for Treating Cancer

What explanation can we offer for the steady increase in survival rates among can cer patients? One answer likely is the improve ments scientists have made in cancer detection. These improvements include a variety of new imaging techniques as well as blood and other tests that can help physicians detect and diagnose

cancer early. Although many Americans regularly watch for the early symptoms of cancer, by the time symptoms occur many tumors already have grown quite large and may have metastasized. Likewise, many cancers have no symptoms. Clearly, great effort is needed to educate Americans that cancer screening (checking for cancer in people with no symptoms) is key to early detection.

 

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Another explanation for increased survival is improved treatment. Today, the traditional workhorses of cancer treatment—surgery, radiation, and chemotherapy—are being used in ways that are increasingly specific to the type of cancer involved. In fact, many cases of cancer now are being fully cured.

A key area of interest lies in learning how to exploit the molecular abnormalities of cancer cells to bring about their destruction. For example, understand ing the role of oncogenes in the development of cancer suggests new targets for anticancer therapies. Some drug companies are working on drugs designed to shut down abnormal receptor proteins. Other potential targets are the aberrant proteins within the cytoplasm that transmit stimulatory sig nals even without being stimulated by surface receptors.

 

One bold new research initiative that offers significant promise is the Cancer Genome Anatomy Project (CGAP). The project's goal is to identify all the genes responsible for the establishment and growth of human cancer. The work is based on a simple concept: Although almost every cell in the body contains the full set of human genes, only about one-tenth of them are expressed in any particular type of cell. Thus, different types of cells— for example, muscle cells and skin cells—can be distinguished by their patterns of gene expression.

 Establishing for a particular cell the repertoire of genes expressed, together with the amount of normal or altered gene product produced by each expressed gene, yields a powerful "fingerprint" or "signature" for that cell type. Not unexpectedly, during the transformation of a normal cell to a cancer cell, this signature changes. Some changes are quantitative. That is, gene A may be expressed in both cells, but at greatly different levels, or it may be expressed in one cell but not the other. Other changes are qualitative: Gene B may be expressed at the same level in both cells, but produce an altered product in the cancerous cell.

 

Scientists expect that being able to "read" these signatures—in other words, being able to compare the signatures of cells in their normal and cancerous  states—will change cancer detection, diagnosis, and treatment in many exciting ways. Specifically, studying the exact sequence of molecular changes a cell undergoes during its transformation to a can cerous state will help scientists identify new molecular-level targets for prevention, detection, and treatment. One observation scientists have recently made is that cells surrounding an incipient tumor also may undergo changes that indicate that cancer is present. For example, early tobacco-induced molecular changes in the mouth may predict the risk of developing lung cancer, and cancers of the urinary tract may be signaled by molecularly-altered cells that are shed in the urine. Reading the signatures of these easily accessed cells may enable scientists to develop simple, non-invasive tests that will allow early detection of cancerous or precancerous cells hidden deep within the body.

 Reading such signatures will also enhance the specificity of cancer diagnosis by allowing scientists to differentiate among tumors at the molecular level. By assessing the meaning of individual changes in a cell's signature, scientists will be able to determine which cancers are most likely to progress and which are not—a dilemma that confronts doctors in the treatment of prostate can cer—thereby allowing patients to avoid the harmful consequences of unnecessary treatment.

 

Finally, molecular fingerprinting will allow researchers to develop new treatments specifically targeted at cellular subtypes of different cancers. Often, patients suffering from tumors that by traditional criteria are indistinguishable, nevertheless experience quite different outcomes despite having received the same treatment. Research indicates that these different outcomes sometimes are related to the presence or absence of particular gene products. In the future, such molecular characteristics likely will be used to identify patients who would benefit from one type of treatment as compared with another.