At the April 2019 American Association of Cancer Research (AACR) meeting, promising vaccines and chemopreventive strategies were presented. The chair of the Molecular and Cellular Mechanisms in Cancer Prevention Research Session, Dr. Zvi Livneh, defined the term “cancer prevention,” which in a classic sense, refers to the prevention of disease in a healthy person prior to the onset of any symptoms (primary prevention).

It is important to note that natural anti-cancer mechanisms operate remarkably well to maintain the integrity of complex tissues and organs. For example, noxious carcinogens can be detoxified before they can damage DNA, and repair mechanisms fix any damaged DNA to maintain the integrity of the cell. Responses such as cell suicide and senescence are activated by oncogenic signaling pathways. Antigen-specific immunity recognizes and eliminates cancer/precancerous cells. Collectively, these naturally existing tumor‑suppressive mechanisms can be deployed to develop viable and applicable cancer preventive strategies.

Dr. Martha Gay presented data on the efficacy of the agent, proglumide, in the prevention of nonalcoholic steatohepatitis. The drug, an orally available cholecystokinin (CCK)-receptor antagonist, has been used in the past for the treatment of stomach ulcers and has a good safety profile. This drug was found to prevent fibrosis and steatosis in C57BL/6 mice fed the choline-deficient, ethionine-supplemented (CDE) diet. Interestingly, endogenous CCK has also been implicated in pancreatic cancer, and proglumide was found to also reduce fibrosis in the pancreatic tumor microenvironment. Future studies may identify a potential application of this drug in chemoprevention of liver and/or pancreatic cancer.

Apalutamide (ARN509) is a next generation androgen receptor antagonist discovered in the laboratories of Drs. Michael Jung (UCLA) and Charles Sawyers (MSKCC) and approved by the FDA in February 2018 for the treatment of non-metastatic castration-resistant prostate cancer. Dr. David McCormick and colleagues used either intermittent or continuous dosing of ARN509, which demonstrated potent cancer prevention efficacy in the Bosland mouse model of prostate carcinogenesis. Having a desirable safety profile, ARN509 merits consideration for evaluation in human prostate cancer prevention trials.

A frameshift neoantigen vaccine that could potentially prevent Lynch syndrome (LS) was developed by Dr. Steve Lipkin from the Weill Cornell Medical College in New York City, in collaboration with the German Cancer Research Center in Heidelberg, Germany. LS is an autosomal-dominant cancer predisposition syndrome caused by germline mutations in the DNA mismatch repair (MMR) genes, resulting in a defect in DNA MMR, conferring a 70–80% lifetime risk of developing colorectal cancer (CRC) and comprising 2–5% of all CRC cases. Using a dMMR (deficientMMR) mouse intestinal tumor model, the investigators developed a peptide vaccine targeting four frameshift peptide neoantigens. The FSP vaccine adjuvanted with CpG ODN in combination with naproxen significantly improved overall survival for mice with LS vs. vaccination alone. The promising results will hopefully translate to a vaccination strategy that can be tested in individuals with LS. Interestingly, Dr. Marcia Cruz-Correa, who talked about the importance of prevention, early detection, and interception at the conference wrap-up session, highlighted the FSP vaccine and apalutamide as promising preventive agents.

Advances in cancer therapeutics are creating unprecedented options for treating cancer patients, particularly in developed nations. However, given the meteoric rise in cancer worldwide, the economic cost of treating cancer, not to mention the pain and suffering of patients with disease, effective preventive strategies may be key to cancer control. As Bill Gates rightly said, “Treatment without prevention is simply unsustainable.”

%d bloggers like this: