VIDEO

Chaos to Cure: Bringing Basic Research to Patients

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Cancer Grows by Organized Chaos

Sharon had little use for doctors. She was in her seventies and had always been healthy. Most members of her family lived into their nineties, and she expected to do the same. She saw her family doctor only for problems and declined recommended cancer-screening tests.

For several weeks Sharon experienced stomach bloating and diarrhea. She began to feel weak and was losing weight. Sensing that something was wrong, she saw her doctor, who performed a fecal blood test, which, if positive, could indicate the presence of colon cancer. The test showed blood in her stool. Sharon was referred to a gastroenterologist for a colonoscopy. Midway through the test, the snakelike “scope” could no longer be advanced because a tumor was blocking it. The biopsy showed cancer; the tumor would have to be removed.

The surgeon removed part of Sharon’s colon, including the tumor and many nearby lymph nodes, receptacles for cells draining from the cancer.

The pathologist noted that the tumor was an invasive colon cancer (adenocarcinoma) that had spread to several lymph nodes. The main tumor also contained remnants of a benign polyp, called an adenoma.

This meant that the invasive cancer developed out of the benign polyp (it also indicated that cancer might have been averted had she undergone a screening colonoscopy). In the final analysis, Sharon had stage III colon cancer, and chemotherapy was recommended in an attempt to prevent her cancer from returning and being a greater threat to her life.

If we could have magically implanted a camera into Sharon’s colon twenty years earlier and followed the development of her cancer, what would we have seen? We would have witnessed the gradual advance of a small, benign growth into a large cancer through an organized process called “the polyp cancer sequence”. The polyp cancer sequence is akin to a great tree rising from a small sprout. (A small percentage of colon cancers do not form polyps first but instead form flatter growths, called “flat adenomas,” which gastroenterologists can detect during colonoscopy.)

With that magical camera, we would have seen a cell that normally lines the colon wall becoming activated to duplicate itself many times over and grow into a small heap the shape of a broccoli stalk: the polyp.

In the beginning, a polyp is small, about the size of a pea. At this early stage, it rarely contains cancer. As the polyp grows, the chances increase that it will harbor cancer, as indicated below:

The Risk of Cancer in a Colon Polyp

Polyp size – Similar to – Chance of harboring cancer

Less than 1 cm – pea – less than 1 percent

1–2 cm – grape – 5 percent

More than 2 cm – peach pit or bigger – 10–20 percent

If large polyps are not removed, a substantial number will pass from the first to the second phase of cancer growth and develop into a malignancy. Once cancer is established inside a polyp, it can grow in two ways: (1) it can expand inside the colon to form a large tumor that interferes with bowel movements and causes symptoms, such as those Sharon experienced; and (2) it can spread to other areas of the body (metastasize), first to nearby lymph nodes and then to such distant organs as the liver.

If we are to find a cure for cancer, then we need specific answers to the following questions:

• What causes the first cell to initiate the polyp sequence?

• What moves it along to enlarge the polyp at each step?

• What ultimately transitions the polyp into cancer?

• What makes the fully formed cancer spread and become a threat to life? These questions are more commonly phrased in regard to any cancer:

• Why did the cancer start?

• What makes it grow?

• Why do some cancers metastasize?

The answer to all these questions revolves around DNA. The inception, growth, and spread of cancer are interconnected by a common thread, their shared ancestry, their shared DNA.