Intercepting Cancer by Tackling Precancer

Guest Post by William G. Nelson, MD, PhD
Editor-in-Chief, Cancer Today

Clearly, cancers that have metastasized, or spread, to many different organ sites are difficult to cure. These cancers typically contain thousands of defective genes that drive malignancy and undermine attempts at treatment. Can these cancers be intercepted before they progress to a malignant state?

Many of the most common cancers are heralded by premalignant conditions. Precancerous cells, though unable to invade organs and tissues or spread throughout the body to threaten life, nonetheless share many features with cells in life-threatening cancers, including uncontrolled growth. The premalignant cells also acquire gene defects similar to those seen in full-blown cancers. As these gene defects are better understood, treating premalignancy may prove to be the most promising tactic for cancer interception—intervening early to stop cancers before they fully develop.

Most successful cancer prevention thus far has focused on minimizing avoidable risks for cancer development. Population research has identified several cancer causes—such as cigarette smoking, viral infections, and carcinogens in the diet or workplace—and this has enabled effective cancer prevention. Studies of inherited predispositions to cancers have identified further opportunities for cancer prevention using prophylactic surgery. As an example, removal of otherwise healthy but nonetheless cancer-prone tissues from the breasts, ovaries, and fallopian tubes can reduce cancer risk for carriers of defective BRCA genes.

Cancer interception, via the systematic targeting of premalignancy, offers a chance to confront an even greater range of cancer types. Already, treatment of premalignant conditions has proven effective in reducing the risk of developing many full-blown cancers. Drugs that treat precancerous conditions of blood-forming cells can limit progression to leukemia or multiple myeloma. At solid organ sites, precancerous lesions tend to resemble cancers in many ways. Although they are incapable of growing invasively, these lesions can give rise to invasive cancers. For this reason, if they can be removed, the risk for life-threatening cancer is often reduced. Removal of polyps from the colon to prevent colorectal cancer is an example of this approach.

To best tackle premalignancy, research on the gene defects acquired by precancerous cells must be intensified. Just as cataloguing gene defects in established cancers has led to precision treatments guided by the specific gene alterations present in individual cancer cases, taking inventory of gene alterations in premalignant lesions could lead to similar benefits. In addition, the spectacular responses of some metastatic cancers to immunotherapy highlight the need for deeper studies of how the immune system recognizes and responds to premalignancy. Perhaps new immunotherapy approaches could reduce or eliminate precancerous lesions and other precancerous conditions.

Ramping up research on premalignancy offers the best response to a challenge issued almost a decade ago by Elizabeth Blackburn, PhD, a Nobel laureate and Past President of the American Association for Cancer Research, which publishes Cancer Today: “Although treating or even curing cancer is often, understandably, at the forefront of people’s minds, cancer will never be brought under control unless the other side of the equation is addressed: intercepting, or preventing, it.”

William G. Nelson, MD, PhD, is the editor-in-chief of Cancer Today, the quarterly magazine for cancer patients, survivors, and caregivers published by the American Association for Cancer Research. Nelson is the Marion I. Knott professor of oncology and director of the Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins in Baltimore. You can read his complete column in the winter 2020/2021 issue of Cancer Today.