Short term fasting, IGF/insulin-axis and therapy outcome in patients with cancer

Groot, S. de (2021)

Doctoral Thesis

This thesis describes the effects of shortterm fasting on chemotherapy outcome in patients with breast cancer and the IGF-1 and insulin pathway as a target for cancer therapy and as a biomarker for chemotherapy outcome.

Preclinical research is evaluated, which shows that short-term fasting during chemotherapy is effective. The effects of short-term fasting in humans is not evident yet. Although the first small clinical studies of short-term fasting as adjunct to chemotherapy are promising in terms of decreased toxicity and enhanced efficacy, the exact mechanism and effects are not established yet. More studies and a longer follow-up are needed to prove this.

Insulin-like growth factor 1 (IGF-1) and insulin are members of the IGF-1 pathway, which is involved in cell growth and proliferation. The effects of the IGF-1 pathway on chemotherapy outcome and the pathway itself as target for cancer therapy are described. The disappointing results of clinical studies of IGF-1R inhibitors may be caused by the complexity of the IGF-1R pathway. Lowering both insulin and IGF-1, perhaps with a short-term fasting intervention, serves as a possible target in cancer therapy.

• Short-term fasting
• Fasting–mimicking diet
• Chemotherapy
• Differential stress resistance (DSR)
• Breast cancer
• Ewing sarcoma
• Toxicity
• Efficacy
• IGF1
• Insulin

• All authors: Groot, S. de
• Supervisor: Pijl, H.; Hoeven, J.J.M. van der
• Co-supervisor: Kroep, J.R.
• Committee: Gelderblom, A.J.; Wall, E. van der; Kampman, E.
• Qualification: Doctor (dr.)
• Awarding Institution: Faculty of Medicine, Leiden University Medical Center (LUMC), Leiden University
• Date: 2021-09-01
• Sponsorship: Pink Ribbon (2012.WO31.C155), Dutch Cancer Society (2010-4682), Amgen, Novartis, Sanofi Aventis