Stopping Cancer Before It Starts by Understanding the Biology of Precancerous Lesions

Cancer remains one of modern medicine's greatest challenges. Many researchers and doctors now seek ways to stop the disease before it progresses rather than treating established cancer. One area of research focuses on the importance of the stage called "precancer", particularly in common cancers such as breast cancer. Precancer refers to a precancerous period when cells have not yet become cancerous but have begun growing abnormally. Understanding and targeting this stage could revolutionize future cancer treatment.

This article draws on groundbreaking work by Dr. Christina Curtis and her Stanford University team investigating the biology of precancer in breast cancer. On May 31, 2024, Science published the research, which focuses on understanding cancer's genetic foundations and discovering ways to stop it before it begins.

Breast Cancer: The Genetic Foundations of Divergence

We know that certain breast cancer types recur more often than others. Yet why some are more aggressive has remained incompletely understood for many years. Dr. Christina Curtis and her Stanford team made important discoveries while seeking an answer.

Questioning cancer's origins, Dr. Curtis asks, “They are all breast cancer, all estrogen receptor-positive. But these groups are different. When did they diverge, and how was that determined?” The findings show how inherited genetic differences influence the immune system and thereby shape breast cancer type and aggressiveness. Curtis's work reveals that inherited DNA, known as the "germline genome", shapes tumor evolution.

The Precancerous Stage: A Revolution in Treatment Strategies

This research is part of a growing effort to understand precancer biology. Understanding the biological properties of precancerous cells could open the way to treatments that stop cancer before it begins. Researchers hope to design therapies targeting this critical stage. While biotechnology startups develop new tests to detect cancer early, Dr. Curtis and her team aim to prevent its onset.

The number of biologically based preventive treatment approaches is expected to grow over time.

Using the Immune System to Stop Cancer

Stanford researchers aim to find ways to stop cancer using the immune system. Their work focuses on DNA changes known as "somatic aberrations" or "single nucleotide polymorphisms" (SNPs). For example, HER2 may contain SNPs, and these changes can affect how the HER2 protein regulates breast cell growth and division.

Dr. Curtis and colleagues showed that these genetic changes, which can have important effects on the immune system, may occur in particular epitopes (protein features capable of triggering an immune response). Their work introduces a concept important in cancer treatment called "germline epitope burden".

Immune Surveillance: Treating Cancer Through the Immune System

Research shows that the immune system can recognize certain epitopes and eliminate cancer.

Sometimes, however, cancer cells overcome this high epitope burden and tumors become more aggressive. Cancer develops at this point. Dr. Curtis describes this as "a critical junction between preinvasive and invasive disease" and emphasizes that it may be the ideal time to intervene.

The Future of Precancer Research

Stanford's findings add to previously known biomarkers and may enable detection of "malignant tumors" with a simple blood test. According to Dr. Curtis, "This could also contribute to discovering new epitopes that affect the immune system and developing future vaccines."

Many laboratories are working to understand precancer biology and develop potential vaccines. For example, the University of Washington's Cancer Vaccine Institute is developing a vaccine for a precancerous lesion associated with many ovarian cancers.

At the University of Pennsylvania, Dr. Domchek is investigating whether breast cancers caused by BRCA 1 and 2 mutations can be stopped early. Her team is testing a vaccine in healthy people with these mutations that targets telomerase, an enzyme overexpressed in 95% of cancers. The hope is that this experimental vaccine could reduce cancer risk.

Dr. Ming Yu of Fred Hutchinson Cancer Center studies the effects of senescent cells on the immune system. Having discovered that senescent cells accumulate and create a microenvironment that promotes tumor formation, Yu is testing an anti-aging drug called rapamycin in mice to eliminate these "zombie cells." Dr. Yu expects to determine within a few months whether this "cleanup" prevents cancer.

Conclusion: Early Intervention as a Future Treatment

All this work could open a new era in cancer treatment. Dr. Domchek highlights the importance of early intervention, saying, “Most drug development begins with advanced cancer patients and moves toward earlier stages. But perhaps we have been thinking about it the wrong way from the start, and what we really need is to understand the distinctive biology of early lesions,” emphasizing the value of intervening early.

These groundbreaking studies suggest that stopping cancer at the precancerous stage may be possible. In the future, their findings could lead to strategies that prevent cancer before it starts and save millions of lives.