Cancer prevention is a critical component of our effort to reduce the burden of cancer in the United States and globally. As a measure of its importance, cancer prevention has the potential, in the long run, to save even more lives than treatment. Effective prevention will also reduce cancer incidence and morbidity, meaning fewer people will have to face the physical, financial, social, and psychological harms of a cancer diagnosis and treatment.
One approach to cancer prevention is reducing or eliminating exposures to cancer-causing substances in the environment, such as asbestos, tobacco smoke, and radon gas. Another approach is to protect the body against such exposures or reduce their effect. For example, using sun screen to protect the skin against ultraviolet radiation and getting vaccinated against cancer-causing viruses, including certain types of human papillomavirus (HPV) that cause cervical and several other types of cancer, can protect against processes that can eventually lead to cancer. In addition, some cancer screening tests, such as the Pap smear for cervical cancer and colonoscopy for colorectal cancer, can aid in cancer prevention. These tests detect premalignant lesions that can be removed or destroyed before they progress to cancer.
Reasearch in the field of cancer prevention is often not feasible in the private sector due to the many economic, logistical, and scientific challenges that must be overcome. Therefore, NCI’s commitment to cancer prevention research is particularly important. In addition to supporting basic and translational prevention research, NCI supports cancer prevention clinical trials through programs such as the NCI Community Oncology Research Program (NCORP), a national network that brings prevention trials to communities across the United States. The return on NCI’s investments in cancer prevention can be seen in the declining incidence and mortality of several types of cancer, most notably lung, colorectal, and cervical cancer.
Although we have made tremendous progress in cancer prevention, many opportunities lie before us to make even greater progress. Just as we are increasingly able to identify the best treatments for a person’s cancer based on the genetic abnormalities of their tumor, fully characterizing a person’s genetic makeup and understanding their environmental exposures over time should enable us to tailor personalized measures to screen for and prevent cancer. This is what we refer to as “precision prevention.”
Progress in Preventing Cancer
NCI funding has supported major advances in cancer prevention, including the development of a hepatitis B virus vaccine to prevent liver cancer; demonstration that the drugs tamoxifen and raloxifene can reduce the risk of breast cancer in women at increased risk of the disease; and development of HPV vaccines to prevent the majority of cervical, vaginal, vulvar, anal, rectal, oropharyngeal (throat), and penile cancers. Recent NCI-funded research accomplishments are highlighted below.
Screening for Barrett Esophagus to Prevent Esophageal Cancer
The incidence of esophageal adenocarcinoma (EAC), the most common form of esophageal cancer in the United States, has been increasing for the past four decades, particularly among white men. Most patients diagnosed with EAC have a poor prognosis, with a 5-year relative survival rate of 17%. The only established precursor for EAC is Barrett esophagus (BE), a condition that affects an estimated 1%–5% of the general population and is typically diagnosed in individuals with chronic acid reflux symptoms. However, a prior history of BE has been documented in only a minority of patients who develop EAC. The progression of BE to EAC occurs at a rate of less than 1% per year; therefore, most people with BE require only infrequent endoscopic monitoring to check for disease progression.
In 2018, NCI-funded researchers reported that, among individuals whose BE progressed to EAC, most had high levels of genomic abnormalities detected in their BE lesions 4 years before the development of cancer. This finding could provide doctors an opportunity to intervene to destroy these lesions and prevent EAC. In 2018, another NCI-supported research team led by investigators at Case Western Reserve University in Ohio used an experimental, swallowable, balloon-like sampling device to check esophageal tissue for modification (i.e., methylation) of the DNA in two genes, CCNA1 and VIM, each of which is a biomarker for BE. The researchers proposed that this approach could be a cost-effective, sensitive, and well-tolerated way of screening for BE in at-risk individuals.
Preventing Lung Cancer with a Vaccine
Lung cancer, the leading cause of cancer death worldwide, currently accounts for about 25% of all cancer deaths in the United States. Up to 30% of human lung cancers are driven by mutations in the KRAS gene, almost all of which cause a change in amino acid 12 or 13 of the KRAS protein sequence.
In 2017, NCI-funded researchers at the Medical College of Wisconsin and the NCI intramural research program reported the development of an experimental vaccine that targets KRAS protein bearing one of these mutations; specifically, at position 12 of the protein sequence, the amino acid glycine is replaced by the amino acid aspartate. This mutant protein is called KRAS G12D. In a mouse model in which the mutant protein can be activated, administering the vaccine before activating the mutant protein reduced both the number of lung tumors that formed and tumor size by more than 80% without adverse effects.
Although preliminary, these findings suggest that a vaccine to prevent KRAS G12D-driven lung cancers or to prevent their recurrence may be feasible. In addition, such a vaccine may prove useful in preventing the development or recurrence of the approximately 15% of colorectal cancers that are also driven by KRAS G12D. The results should also encourage the development of additional vaccines that target this and other mutant KRAS proteins.
Preventing Polyp Formation in Familial Adenomatous Polyposis
Familial adenomatous polyposis (FAP) is a hereditary condition that predisposes individuals to the development of numerous polyps in the gastrointestinal tract and increases their lifetime risk of several cancer types, including a 100% risk of colorectal cancer and a 5%–12% risk of cancer of the duodenum (i.e., the upper part of the small intestine).
In 2016 and 2018, the results of an NCI-funded phase 2 clinical trial conducted by researchers at the Huntsman Cancer Institute at the University of Utah showed that treating patients for 6 months with sulindac, a nonsteroidal anti-inflammatory drug (NSAID), and erlotinib (Tarceva), a targeted therapy that blocks the activity of a protein called epidermal growth factor receptor (EGFR), reduced the burden of polyps in the small intestine, colon, and rectum by about 70% compared with patients who were given a placebo. Read how Gregg from Utah benefited from the combination treatment tested in the NCI-funded clinical trial.
Previous NCI-supported research had shown that EGFR plays an important role in colon tumor formation and progression and that blocking the activity of this protein might be useful in preventing colorectal cancer in people at increased risk of the disease. Additional research is needed to determine whether the malignant potential of the polyps that were prevented with sulindac and erlotinib is similar to that of the polyps that were not prevented.
NCI is supporting research to address this question and to further investigate this and other chemopreventive approaches aimed at reducing the risk of gastrointestinal cancers in people at increased risk, including individuals with FAP.
Preventing All HPV-Associated Cancers
Although three effective human papillomavirus (HPV) vaccines have been approved by the Food and Drug Administration to date, none provides protection against all 13 identified high-risk (i.e., cancer-causing) HPV types. To provide greater protection, an international team of researchers with NCI support recently developed a vaccine called RG1-VLP (also known as RGVax) that consists of virus-like particles (VLPs) made from proteins that form the outer shell of HPV type 16 (HPV16).
Specifically, the VLPs are composed of the protein HPV16 L1 into which a segment of the protein HPV16 L2 has been inserted. In preclinical studies, the vaccine protected against infection by more than 20 types of HPV, including all 13 high-risk types. A second-generation vaccine, which also has the potential to prevent all HPV-associated cancers, will be tested in clinical trials in early 2019.
Opportunities for Greater Progress
Thanks to basic research, our understanding of how cancers develop continues to grow. This increasing knowledge, together with the availability of powerful new technologies, is affording new opportunities to improve and expand our ability to prevent cancer. In addition to developing new methods of cancer prevention, we must overcome the barriers to implementing established approaches, such as the use of approved cervical and colorectal cancer screening tests and preventive vaccines, particularly in populations where they historically have been underutilized. Areas of opportunity for additional progress are described below.
Increasing knowledge, together with the availability of powerful new technologies, is affording new opportunities to prevent cancer.
Understanding the Biology of Precancerous Lesions and their Progression to Cancer
Fully understanding the events that underlie the development of precancerous tissue changes and drive the transition to malignant disease will provide new opportunities for cancer prevention. This knowledge will also lead to the identification of molecular markers that will be useful in cancer risk assessment and early detection.
Toward this end, NCI has announced its intention to fund Pre-Cancer Atlas Research Centers as part of the Human Tumor Atlas Network, which was established under the Cancer Moonshot℠. These research centers will systematically collect, catalogue, and comprehensively analyze large numbers of precancerous lesions and early cancers, including their microenvironments, that have developed at specific organ sites.
Identifying Risk Factors for Cancer
Identifying genetic and environmental risk factors for cancer and understanding how genes and the environment interact to influence cancer risk will enable the development of new approaches to prevent cancer. This knowledge will also lead to more precise assessments of cancer risk, allowing people at increased risk of cancer to receive the most appropriate medical care to manage their risk.
More research in this area is needed, and several NCI programs support and pursue this type of research, which includes the development and validation of tools that can be used to assess risk at various stages of a person’s life, within population subgroups, and across the general population.
Developing New Approaches to Cancer Prevention
It has been estimated that 30%–50% of cancers that occur today could be prevented by not smoking cigarettes, maintaining a healthy body weight, reducing exposures to environmental risk factors, and receiving recommended screenings and vaccinations. To reduce the incidence of these cancers, we must find innovative ways to help people change their behaviors and make healthy lifestyle choices.
An estimated 30%–50% of cancers that occur today could be prevented.
Additional research is also needed to address the 50%–70% of cancers that are not currently preventable. NCI supports a broad portfolio of research to increase our understanding of their underlying biology, develop new drugs or repurpose existing drugs for cancer chemoprevention, and develop new cancer prevention vaccines.