通过控制癌前病变拦截癌症

显而易见的是，已经转移或扩散到许多不同器官的癌症是难以治愈的。这些癌症通常包含数千个缺陷基因，此类缺陷基因导致恶性肿瘤并降低治疗效果。这些癌症能否在恶化之前被拦截？

许多最常见的癌症都会先发生癌前病变。癌前细胞虽然不能侵入器官和组织，也不能扩散到全身而危及生命，但与致命的癌细胞有许多共同的特点，如不受控制的生长。癌前细胞也会获得与病变癌症相似的基因缺陷。随着对这些基因缺陷的深入了解，治疗癌前病变可能是拦截癌症的最有希望的策略，即在癌症完全形成之前就进行早期干预，阻止其发生。

到目前为止，大多数成功的癌症预防措施都着力于将癌症发生中可避免的风险降至最低。人群研究已经确定了几种致癌原因，如吸烟、病毒感染、饮食或工作场所中的致癌物等，这使得有效的癌症预防成为可能。对遗传癌症倾向的研究已经发现了利用手术预防癌症的更多方法。例如，从乳房、卵巢和输卵管中切除虽正常但易患癌的组织，可以降低BRCA基因缺陷携带者的患癌风险。

英文原文如下

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.