Prevention and Treatment of Breast Cancer
Abstract
Rationale: From the earliest collection of breast cancer incidence data, it has been noted that women who had given birth were at lower risk for breast cancer than women who never gave birth. While there may be many factors during the complex process of pregnancy that contribute to the decrease in breast cancer incidence later in life, it is clear that the major factor is a pregnancy-associated protein called alpha-fetoprotein or AFP. Epidemiological studies and direct measurements clearly demonstrate that pregnancy-associated protection from breast cancer is proportional to the concentration of AFP crossing from fetal into maternal serum to which the mammary gland is exposed and that AFP acts in an endocrine manner to extinguish premalignant cells in the breast that, much later in life, would have gone on to develop into cancer. We have invented a molecule called AFPep that is the active site of AFP and that has all the anti-cancer activity of the full protein. AFPep is safe and non-toxic because it is a piece of a naturally occurring protein. A game-changer aspect of this proposal is that AFPep is safe enough to use as a preventive and effective enough to be used as a therapeutic. Objective: Impressively, AFPep has been shown to prevent carcinogen-induced breast cancer in rats, but women are not often exposed to high doses of potent carcinogens. We need to document that AFPep can prevent the estrogen-promoted kind of breast cancer that women frequently experience. Additionally, we believe that AFPep will stop the progression of cancer (from normal tissue --> benign lumps --> precancerous lumps --> cancer) at any stage, and we will test this concept using an innovative model in rats. AFPep also stops the growth of human tumors growing as xenografts in rodents, but we need to demonstrate that AFPep will stop growth of spontaneous, heterogeneous tumors growing in higher mammals, so we plan to use AFPep to stop the growth of breast cancers in veterinary patients (dogs). Overarching Challenge: This is a low-risk, high-reward proposal that will meaningfully address the Overarching Challenges of primary prevention of breast cancer and replacement of drugs that exhibit toxicities with a safe, effective, and durable intervention. Clinical Applications, Benefits, and Risk: The outcome of this research effort will be a pill (much like a vitamin) that can be taken by all women with the intention of preventing breast cancer (obtaining protection similar to that offered by multiple pregnancies) without fear of side effects. Still, not all women will take advantage of this preventive agent, so for women who experience a diagnosis of "dense breast," or who may have family members with breast cancer or have other risk factors, the awkward, uncomfortable experience of "watchful waiting" could be replaced by safe, effective intervention with oral AFPep. And for women who develop overt breast cancer, existing drugs could be supplemented with or replaced by AFPep. Indeed, AFPep continues to be effective after tumors have developed resistance to tamoxifen. To date, all evidence indicates that AFPep is extremely well-tolerated, so the risks of this intervention are minimal. The benefits are substantial, either for women who experience breast cancer or for those who hope never to encounter that diagnosis. Time to Patient-Related Outcome: This research project was developed over the past several years with Congressionally Directed Medical Research Programs (CDMRP) support (Concept, Idea, and other awards). We are very close to a major breakthrough, but we need to document efficacy in higher mammals and in realistic prevention models. After completion of this study, the next steps in translation to clinical utility of AFPep would entail acquiring an Investigational New Drug (IND) license from the Food and Drug Administration based on thorough preclinical toxicity assessment (which would take 1 year), leading to Phase I
Document Details
- Document Type
- DoD Grant Award
- Publication Date
- Mar 29, 2016
- Source ID
- W81XWH1510242
Entities
People
- Thomas Andersen
Organizations
- Albany Medical College
- United States Army