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Figure 11. Density visualization of “resveratrol” and co-occurring words by VOSviewer. Co-occurrence words with resveratrol are
displayed based on text data from Web of Science. The color illustrated in the figure changes from blue to yellow based on the frequency
with which as a word is linked to resveratrol

Conversely, dietary chemopreventive agents may influence the actual composition, and therefore the
metabolic capacity, of the gut microbiome. For example, in studies we have conducted with mice in which
the diet was supplemented with whole grapes (unpublished), the overall organization of the gut microbiome
was clearly altered [Figure 13]. This is yet another factor that needs to be considered in defining the overall
action of chemopreventive agents.

Sequelae
Over the past decades, there have been significant advancements in understanding cancers and in
improving early detection, treatment, and prevention. As a result, the survival rate of cancer patients has
increased. And, as the number of cancer survivors increases, the quality of life for these individuals must
receive greater attention, given that adverse effects (sequelae) are frequently encountered during or after
chemotherapy. One common sequela is cancer-related cognitive impairment (CRCI), or chemotherapy-
induced cognitive impairments, colloquially called “chemobrain” or “chemofog”, a decline in cognitive
function following cancer treatment. Central neurotoxicity can remain as long-term sequelae following
the termination of treatment. For example, it has been reported that breast cancer and childhood cancer
survivors may experience cognitive dysfunction [282] . Notably, some chemopreventive agents are at least
touted to improve this condition [283,284] .

Given the mode of action of chemopreventive agents, it seems logical that acute or chronic side-effects
resulting from some forms of cancer chemotherapy could be ameliorated by concomitant administration.
However, since chemotherapy is often designed to be overtly toxic, and therapeutic indices may be low, an
effective chemopreventive agent could actually have an adverse effect on outcome by negating anti-cancer
drug action. An appropriate balance is necessary, but some promising results have been described. For