Frontline Cancer: It is time to better understand pre-cancer

FRONTLINE CANCER:

Although the war is far from won, modern medicine knows a lot more these days about how to fight cancer. Our weapons are more numerous and more precise, from laser surgeries to proton beam radiation to new drugs like checkpoint inhibitors that boost the immune system's own remarkable powers.

Over the past two decades, the overall cancer death rate has steadily declined.

Much of this progress, of course, is based upon research and treatment of patients already diagnosed with cancer. But the best way to conquer cancer is to prevent it from happening in the first place. And here, medical science lags.

A major limitation to the early detection and prevention of cancer is the lack of comprehensive knowledge about the molecular alterations that drive cancer development and progression at its earliest stages. In other words, what is happening at the most fundamental levels to turn normal, healthy cells and tissues malignant?

Before there is cancer, there are often premalignant lesions — regions of abnormal tissue that precede the development of invasive cancer. These lesions are found during diagnostic biopsies in patients suspected of cancer and in screening samples of patients at increased risk of cancer. They are red flags. Many of these lesions will not change. They might even regress. But others will transform into cancer.

While doctors and scientists well-recognize the characteristics of many types of pre-cancerous lesions — they know, for example, the difference between melanoma and an atypical mole, and a polyp versus colorectal cancer — understanding of the microenvironment, molecular and genomic alterations that convert a pre-cancerous lesion to cancerous are not well-defined.

In recent years, efforts like The Cancer Genome Atlas or TCGA, a decade-long project to catalogue genetic mutations responsible for cancer, and the Cancer Cell Map Initiative, a similar endeavor involving Moores Cancer Center scientists to understand in full the pathology of cancer cells, have significantly advanced basic research in immune oncology and precision therapy — the idea that every cancer treatment should be unique to a patient and his or her own cancer.

It is time to do something similar for premalignant lesions. We need to better understand the enemy before the enemy is even really the enemy, ready to attack. The recent passage of the 21st Century Cures Act includes significant funding to support the Cancer Moonshot Initiative, an ambitious, long-term effort to dramatically accelerate research and treatments.

In an article published earlier this year in the Proceedings of the National Academy of Sciences or PNAS, colleagues from Moores and other top institutions such as Johns Hopkins and Harvard and I called upon the cancer research and treatment community and its supporters to devote greater attention and resources to prevention.

Part of this effort should be cancer vaccines, which offer undeniable appeal and potential. The human papilloma vaccine, for example, confers almost 100 percent protection against the strains of the virus linked to cancers like cervical, anal and oropharyngeal (parts of the throat, mouth and tongue).

The Human Vaccines Project, a global public-private partnership of academic research centers, industry, non-profits and government agencies launched earlier this year to speed development of next-generation vaccines and immunotherapies for infectious diseases and just recently expanded to cancer. UC San Diego, along with local collaborators like The Scripps Research Institute, J. Craig Venter Institute and La Jolla Institute for Allergy and Immunology will serve as a research hub.

Some cancers are particularly ripe for immediate prevention, such as those caused by Lynch syndrome, a relatively common inherited condition that increases the risk of many cancers, including those of the digestive and gynecologic tracts that respond very well to immune checkpoint therapy and are now a major target for vaccine immune prevention.

Vaccines are also being researched for clonal hematopoiesis, an age-related precursor to leukemia, and even pancreatic cancer, including in premalignant cysts and hereditary causes. Fifteen percent of pancreatic cancer is associated with major inherited mutations, most commonly by far BRCA1/2 in Ashkenazi Jews.

Craig Venter, Steve Schoenberger, Ezra Cohen, Aaron Miller, myself and colleagues in other centers are working together to make personalized prevention vaccines for pancreas cancer, the most deadly cancer with very limited treatment or prevention options.

A premalignant cancer genome atlas (PCGA) should be part of this effort. Already, I and a colleague from Boston were asked by the National Cancer Institute (NCI) to co-chair one of the few Cancer Moonshot Demonstration projects focused on the PCGA, and peers from NCI-designated cancer centers will gather in think tanks and brainstorming sessions to best plot a course forward. This was also a major topic of the recent Biocom/ACS Moonshot Summit event led by Joe Panetta and P. Kay Coleman from Biocom and the American Cancer Society.

In the days and months ahead, when you read about new programs and goals fueled by the cancer moonshot project and 21st Century Cures Act, look to see if there is a prevention element. Someday, we might cure cancer, but it's far better to avoid it altogether.

 

— Scott M. Lippman, MD, is director of UC San Diego Moores Cancer Center. His column on medical advances from the front lines of cancer research and care appears in La Jolla Light the fourth Thursday of each month. You can reach Dr. Lippman by e-mail: mcc-dir-lippman@ucsd.edu

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