According to Greek mythology, Cancer was the crab that the goddess Juno immortalized in the night sky after the lowly creature sacrificed himself in a fabled battle between Hercules and the nine-headed Hydra.  Since Juno was stingy with the number of stars she allotted to the crab’s constellation, the amateur astronomer often looks in vain for a body with claws. Nevertheless, first century physicians, searching for picturesque language to describe their patients’ ailments, found in the crab constellation a name for hard masses covered with tortuous veins – particularly those that seemed to burrow deeply into the body.  And so we came to know cancer, the disease that inspires today’s most sophisticated research in cell biology, by a name that has no scientific meaning whatsoever.

The biggest risk factor: age

Cancer is a problem of birth, growth and death of cells, and occurs because our bodies are in a constant state of renovation, from development as tiny embryos until death many decades later. At first we grow and change shape. Then shape becomes fixed but body maintenance requires cell replacement on a regular, repetitive timetable. The master plans laying out instructions for regular destruction and reconstruction of cells lie in the DNA coiled into chromosomes.  Just as job-site blueprints get smudged, torn and stained, DNA accumulates damage over time. External agents such solar, cosmic and X- radiation, toxic chemicals, some hormone use, and some viruses add to the innate wear and tear.  In some people DNA code errors are built in from birth, handed down from one generation to the next.  Errors in the blueprint lead to the imperfect cells which give rise to cancer.

Errors in cell reproduction are visible everywhere. We call them signs of aging. Crinkles around the eyes, sagging skin, “liver” spots, bunions and so on – all are external, visible reminders that internally, similar changes are underway. It is no coincidence that tobacco smoking, single-handedly responsible for most cancer deaths, also produces conspicuous, premature aging.  The most remarkable thing about cancer is that it occurs so infrequently despite billions of cycles of error-producing cell reproduction in each person.  Fortunately for us, DNA also contains numerous safeguards for getting rid of error-ridden rogue cells before they get out of control.

What makes a cancer diagnosis

While cancer cells are identified under microscopes by changes in their appearance, looks alone do not make a cancer diagnosis. Until abnormal cells acquire the ability to grow unchecked, and to travel to other parts of the body (to metastasize), they are precancerous.  In many cases, pre-cancerous cells never make the transition to cancer, but we are unable to predict with 100% accuracy which ones will and which ones won’t.  A large number of breast abnormalities detected on mammograms will not go on to run wild, but few women will comfortably forgo treatment without 100% accurate prediction of the growth potential of their abnormal cells.

Difficulties in prediction

In addition to the breast, the prostate gland in men and the colon in both sexes are the sites of cell growth abnormalities that can, but do not always, result in cancer. Prostates enlarge with age and develop nodules of cell growth called adenomas. Colons develop polyps – enlargements of the lining protruding into the colon on flat or narrow stalks, with or without adenomas on their surfaces. Intuitively, it seems as if detecting these abnormalities and removing them before they have a chance to become cancerous is a good idea. This thinking drives the screening studies aimed at early treatment of cancer. But many of these common cancers are very slow and indolent in their growth and epidemiologic studies do not bear out the intuitive bias.  Unless a patient is young at the onset of a slow growing cancer, treatment does not necessarily lengthen life. Routine prostate cancer screening has fallen out of fashion because, while removing a cancerous prostate may prevent death from prostate cancer, treated patients do not outlive untreated ones.  Decisions about treatment have to be weighed carefully, with attention paid to age and the potential for harm and diminished quality of life that can go along with cancer treatment.

While all cancers begin slowly, some escape the body’s control mechanisms more easily and become aggressive and difficult to treat.  Primary brain, liver, pancreatic and ovarian cancer fall in this category. Toxic external factors that alter DNA may render cancer cells more resistant to the body’s methods of keeping slower growing cancers in check. Lung cancer from smoking, blood cancers secondary to radiation and some viruses, ovarian cancers stimulated by hormone use, and asbestos-induced lung tumors  gallop along compared to the slow movers like prostate and colon cancer.

Treatment

Currently cancer treatment consists of removing cancers surgically and/or intervening with drugs or radiation to kill the abnormal cells. Both approaches leave something to be desired. Surgery removes a tumor already developed, but not the underlying biology that produced the tumor. Chemotherapy that seems effective at first is often followed by a relapse in which the cancer is less responsive – not surprising since the cells surviving the first rounds of treatment are resistant to the drug’s actions. Radiation induces cell damage in all exposed tissues and accounts for cancer development years later in people who have survived the first bout.

The new paradigm for thinking of cancer is as an age and genetics related derangement of cell growth that is also influenced by environmental factors.  Effective, tolerable treatments require understanding of the individual biology of each person’s cancer.  As the interior of living cells give up their secrets to researchers, we are beginning to see some real successes with drugs such as Gleevec (used for chronic myelogenous leukemia) – drugs aimed at specific pathways in the life of microscopic cancer cells – and also with immunotherapy in melanoma.  Perhaps we will eventually  be able to retire the image of the crab to his home in the sky.

Factors in cancer development