The key to eradicating cancer lies in developing strategies to prevent premalignant diseases from actually becoming cancer in the first place, according to a recent perspective piece published in Proceedings of the National Academy of Sciences (PNAS).

The perspective, “Leveraging premalignant biology for immune-based cancer prevention,” was written by cancer researchers from institutions including the University of California San Diego School of Medicine and Moores Cancer Center.

“Science has devoted tremendous amounts of energy and resources to the treatment of cancer, and in recent years, there has been significant progress. The cancer death rate has steadily declined for more than two decades,” Dr. Scott M. Lippman, director of Moores Cancer Center and co-senior author of the PNAS paper, said in a press release. “But cancer still kills more than half a million Americans each year and afflicts many millions more. If we’re ever to eradicate this scourge, we must work to prevent it from occurring altogether.”

With the development of new research tools, researchers have explained some of the genetic processes underlying the transformation of premalignant lesions into malignant and deadly tumors.

“Oncogenic transformation is a series of steps,” said Dr. Elizabeth M. Jaffee, co-senior author, co-chair of the Cancer Moonshot Blue Ribbon Panel and deputy director of the Kimmel Center at Johns Hopkins University School of Medicine. “The body’s immune system is capable of intercepting pre-malignancies and preventing cancer. It does so countless times every day in all of us. That natural ability is what we want to leverage. Building upon our innate defenses against cancer is the foundation of new immunotherapies, which have shown great promise in a very short time.”

But the authors, whose expertise encompasses immunology, biochemistry, microbiology, genomics, epigenomics, vaccines and medical genetics, as well as computational biology, say much more must be done. Initiatives like The Cancer Genome Atlas (TCGA) and genome-wide association studies (GWAS) that study large groups of patients to identify genetic variants associated with cancer have led to significant therapeutic advances. But the authors claim that the studies should be expanded to identify potential preventive targets that lead to better prevention therapies.

The researchers believe new cancer vaccines will be critical to prevent cancer before it has a chance to start. A good example is the human papilloma virus (HPV) vaccine. It provides almost 100 percent protection against HPV strains that are linked to many cancers including cervical cancer and oropharyngeal (throat) cancers.

The perspective piece mentions several cancers to which preventative premalignant efforts could be launched immediately: Lynch syndrome, an inherited condition, increases risk for gynecologic and digestive tract cancers; clonal hematopoiesis, an age-related disorder, can lead to leukemia; and cervical intraepithelial neoplasia, caused by an HPV infection, can progress to cervical cancer.

The authors insist that today’s research in immune oncology and precision therapy should be expanded to include cancer prevention.

“Prevention research has made strides, but progress has been anecdotal and isolated,” said Lippman. “If the goal is eradication of cancer, we need a radically new focus, investment and approach to premalignant diseases and cancer prevention, one that is supported and sustained by broad, deep efforts like the Cancer Moonshot and Human Vaccines Project.”