Periodic Fasting-Mimicking Diet as a Strategy to Increase the Effectiveness of Hormone Therapies in Estrogen Receptor-Positive Breast Cancer
Abstract
Studies from our laboratories show that courses of fasting or of a fasting-mimicking diet (FMD) increase the ability of chemotherapy to control the growth of breast cancer (BC) while at the same time protecting healthy tissues from the toxicity of these drugs. We have now obtained new, compelling data showing that fasting also makes hormone therapies that are commonly used in BC, such as tamoxifen and fulvestrant, much more active, with tumors that either completely regress in response to these agents combined with fasting (tumor cure) or fail to restart growing after these treatments have been stopped (long-term disease control). In addition, we discovered another major advantage of combining fasting or a FMD with tamoxifen, which is the ability of the former to completely prevent tamoxifen-induced endometrial hyperplasia. Drawing from these results, our project wants to address two of the overarching challenges in BC treatment identified by the Breast Cancer Research Program: (i) to “revolutionize treatment regimens by replacing interventions that have life-threatening toxicities with ones that are safe and effective” (this will be accomplished by introducing in BC treatment a FMD, which is safe and well tolerated) and to “eliminate the mortality associated with metastatic BC.” Our research is designed to help patients with estrogen-receptor positive BC who are treated with hormone therapies, such as tamoxifen, aromatase inhibitors (i.e., letrozole, anastrozole, exemestane), or fulvestrant. In the first place, we want to prove that, by undergoing cycles of a FMD while on treatment with these drugs, patients will have a chance to see their tumors regress much more effectively than they would see with the hormone treatment alone, with many cases of tumors that are actually cured, and that even in those tumors that fail to completely regress, the combined treatment will allow long-term disease control without need for additional toxic treatments. We also want to prove that, in patients who are treated for a tumor that has become resistant to letrozole, adding cycles of a FMD to exemestane (Aromasin, a hormone treatment that is typically used in these cases) could help their tumor become responsive to treatment again. Finally, we anticipate that combining cycles of a FMD to hormone treatments will also allow patients to avoid developing endometrial hyperplasia. The fasting-mimicking diet that we want to test in our project (ChemoLieve™ by L-Nutra, Inc.) has already been largely validated in animals and has been tested in clinical studies in the United States and in Europe, showing excellent tolerability in almost two hundred patients. Therefore, positive results from this project will rapidly translate into a confirmatory clinical study of our new approach, allowing payer reimbursement. Thus, overall, we anticipate major results for our project and strong clinical benefits for patients with estrogen receptor-positive BC, including the possibility to see their tumors finally cured by the addition of a safe and well-tolerated FMD to standard hormone treatments, but also to avoid anxiety-generating and potentially life-threatening side effects, such as endometrial hyperplasia and endometrial carcinoma.
Document Details
- Document Type
- DoD Grant Award
- Publication Date
- Oct 29, 2018
- Source ID
- W81XWH1710623
Entities
People
- Alessio Nencioni
Organizations
- United States Army
- University of Genoa