Dietary and lifestyle- related factors are
key determinants of the risk of developing
cancer, with certain cancers being more
dependent on dietary habits than others1–9.
Consistent with this notion, obesity is
estimated to account for 14% to 20% of
all cancer- related mortality in the United
States7, leading to guidelines on nutrition
and physical activity for reducing the risk of
developing cancer6. In addition, given the
emerging propensity of cancer cells, but not
of normal tissues, to disobey anti- growth
signals (owing to oncogenic mutations)10
and their inability to properly adapt to
fasting conditions11,12, there is growing
interest in the possibility that certain
calorie- limited diets could also become
an integral part of cancer prevention and,
perhaps, of cancer treatment as a means
to increase efficacy and tolerability of
anticancer agents11–13.
Even though in the past decade we
have witnessed unprecedented changes
and remarkable advances in cancer
treatment14,15, there remains a crucial need
for more effective and, possibly, curative
therapy. In this Opinion article, we discuss
the biological rationale for using fasting
or fasting- mimicking diets (FMDs) to
blunt TEAEs but also to prevent and treat
cancer. We also illustrate the caveats of
this experimental approach18,19 and the
published and ongoing clinical studies in
which fasting or FMDs have been applied to
patients with cancer.
Systemic and cellular fasting response
Fasting leads to changes in the activity of
many metabolic pathways associated with
the switch into a mode able to generate
energy and metabolites using carbon
sources released primarily from adipose
tissue and in part from muscle. The changes
in the levels of circulating hormones and
metabolites translate into a reduction
in cell division and metabolic activity of
normal cells and ultimately protect them
from chemotherapeutic insults11,12. Cancer
cells, by disobeying the anti- growth orders
dictated by these starvation conditions,
can ha