EFFECT OF FASTING MIMICKING CONDITIONS ON HORMONE THERAPY EFFICACY AND RESISTANCE ACQUISITION IN BREAST CANCER

The most common cancer diagnosed among women worldwide is breast cancer (BC) with 60-80% belonging to the ER+BC subtype. Development of resistance is the major driver of ER+BC-related death. Well-tolerated treatments that allow concomitant targeting of the heterogeneous cancer cells are needed in order to abolish resistance. Fasting and fasting mimicking diets (FMD’s), acting in a broad way, have shown great potential to protect the healthy cells of the body during chemotherapeutic treatment, while augmenting treatment efficacy, mainly through lowered levels of blood glucose and circulating Insulin-like growth factor-I (IGF-I) availability. In ER+BC the interconnection of the ER signalling and the IGF1R signalling builds up a strong network difficult to target with specifically acting drugs. This work provides evidence that cycles of a vast acting FMD have the potential to postpone development of resistance to specific acting endocrine therapy (ET) and circumvent development of resistance to the combined treatment of ET and non ER+BC-specific drugs in vivo. FMD’s capacity to abolish resistance exists if applied at the onset and but also at later stages when insensitivity to these drugs has been acquired. Concomitant and early targeting exhibits a killing effect in vitro and in vivo, potentially on resistance driving subpopulations.