GENOMICS AND THE FUTURE OF CANCER TREATMENT

Centuries ago, when disease was thought to result from a disruption of the body’s four basic “humors” – fluids that collectively governed health – treatments were designed to bring them back into balance. “Therapies,” some of them ghastly by modern standards, were intended to relieve patients of harmful surpluses of certain humors.

Thankfully, medicine has advanced far beyond that era. However, it’s clear that how we understand or conceptualize a disease affects how we treat it. Those who will look back on our efforts decades from now may marvel at the limitations of our knowledge about the true nature of the diseases we sought to conquer.

Consider cancer. For more than a century, cancers have been classified by the organ or tissue where they begin – the breast, lungs, bone marrow, digestive system, and so on – and therapies have been geared to those specific areas. Fortunately, as we’ve learned more about the basic biological processes at work in cancer, a new perspective has emerged. Soon, we may regard the organ-based conceptions as being as outmoded as the “humors.”

Increasingly, we’re able to study cancer not only at the most fundamental, molecular level but also at the level of interacting systems and networks. We have gained crucial insights, for example, into how the immune system fights cancer and why that fight isn’t always successful. We’ve learned how tumors tap into the body’s bloodstream for nourishment and how those supply lines can potentially be shut off. We’ve learned how tumors communicate with healthy, surrounding tissue, and how that neighboring tissue sometimes abets the cancer process.

The best known of these advances in “systems” biology, perhaps, is genomics, which provides a “snapshot” of gene activity within a cell. As our knowledge grows, there has been a shift away from viewing cancer in terms of the organ where a tumor forms, and toward a concern with the genetic instructions that govern both the growth and division of individual tumor cells and the interaction of the tumor with the person who serves as its unwilling host.

To carry this work forward, we need a far more collaborative approach to research, with an emphasis on rapidly converting basic scientific insights into practical treatments that work in patients. By creating “Dream Teams” of scientists and specialists from different disciplines, Stand Up To Cancer is mobilizing precisely this kind of effort. It is one reason why the program holds so much promise for turning the tide against cancer.

The trend toward a genomic approach to cancer is gaining momentum every day. Research has shown, for example, that certain lung cancers have some of the same abnormal, or mutated, genes as some brain cancers. Gene mutations that sometimes show up in breast and ovarian cancers also occasionally appear in prostate cancers. Such similarities may turn out to be far more significant, from a treatment standpoint, than the fact that the tumors arose in different organs. A striking example of this occurred earlier this year. A patient with metastatic melanoma – an often fatal cancer that begins in the skin – came to Dana-Farber Cancer Institute, in Boston, for treatment. Genetic tests showed that her tumors harbored a mutated gene called KIT, which is often found in patients with chronic myelogenous leukemia (CML). Her doctors treated her with the drug Gleevec, which was originally designed for CML patients with mutations in KIT. The result: her cancer went into complete remission – the first time that has ever been accomplished in metastatic melanoma. She and an increasing number of others like her provide another lesson: every person’s tumor is unique. That is why the goal of “personalized medicine” is so compelling.

Cancer has always been known as an illness of many guises. When we talk about cancer today, we’re actually referring to a family of diseases – more than 400 in all – characterized by the uncontrolled growth and spread of abnormal cells. As we begin to identify cancers by their genetic “signatures” – the specific set of mutated genes within their DNA – it may turn out that there are even more types and subtypes than we currently recognize.

The shift from an organ-focused to a gene-focused approach to cancer is already having a profound effect on the way cancer is treated. The impact can be seen particularly clearly in breast cancer. Not too many years ago, breast tumors were categorized and treated primarily by their size, the degree to which they had invaded surrounding tissue or sloughed off cells into the lymph system, and their appearance under a pathologist’s microscope.