Ci a ion: Na a o Ledesma, S.;
Hamed-Hamed, D.;
González-Muñoz, A.; P uimboom, L.
E ec i eness o T ea men s Tha
Al e Me abolomics in Cance
Pa ien s—A Sys ema ic Re iew.
Cance s 2023,15, 4297. h ps://
doi.o g/10.3390/cance s15174297
Academic Edi o s: Lau a Biganzoli
and Daniel S. Si a
Recei ed: 31 May 2023
Re ised: 7 Augus 2023
Accep ed: 25 Augus 2023
Published: 28 Augus 2023
Copy igh : © 2023 by he au ho s.
Licensee MDPI, Basel, Swi ze land.
This a icle is an open access a icle
dis ibu ed unde he e ms and
condi ions o he C ea i e Commons
A ibu ion (CC BY) license (h ps://
c ea i ecommons.o g/licenses/by/
4.0/).
cance s
Sys ema ic Re iew
E ec i eness o T ea men s Tha Al e Me abolomics in Cance
Pa ien s—A Sys ema ic Re iew
San iago Na a o Ledesma 1,2,* , Dina Hamed-Hamed 1, Ana González-Muñoz 1and Leo P uimboom 2
1
Depa men o Physio he apy, Facul y o Heal h Sciences, Campus o Melilla, Uni e si y o G anada, Que ol
S ee 5, 52004 Melilla, Spain; dhamed@co eo.ug .es (D.H.-H.); [email p o ec ed].es (A.G.-M.)
2
Depa men o Physio he apy, Uni e si y Chai in Clinical Psychoneu oimmunology, Uni e si y o G anada
and PNI Eu ope, 52004 Melilla, Spain; leo@cpnieu ope.com
*Co espondence: snl@ug .es
Simple Summa y:
This e iew is he i s s udy ha has iden i ied he me abolomic changes in
di e en ypes o cance and he use o me abolomic-based in e en ions in hose pa ien s. Pe -
sonalized medicine in e en ions based on me abolomics p o iles a e p oposed o hose su e ing
om di e en ypes o cance . Cha ac e is ic me abolomics and pe sonalized in e en ions and he
po en ial bene i s o esea ching me abolism in cance a e discussed.
Abs ac :
In oduc ion: Cance is he leading cause o dea h wo ldwide, wi h he mos equen
being b eas cance in women, p os a e cance in men and colon cance in bo h sexes. The use o
me abolomics o ind new bioma ke s can p o ide knowledge abou possible in e en ions based
on he p esence o oncome aboli es in di e en cance ypes. Objec i es: The p ima y pu pose o
his e iew is o analyze he cha ac e is ic me abolome o h ee o he mos equen cance ypes.
We u he wan o iden i y he exis ence and success a e o me abolomics-based in e en ion
in pa ien s su e ing om hose cance ypes. Ou conclusions a e based on he analysis o he
me hodological quali y o he s udies. Me hods: We sea ched o s udies ha in es iga ed he
me abolomic cha ac e is ics in pa ien s su e ing om b eas cance , p os a e cance o colon cance
in clinical ials. The da a we e analyzed, as well as he e ec s o speci ic in e en ions based on
iden i ied me abolomics and one o mo e oncome aboli es. The used da abases we e PubMed, Vi ual
Heal h Lib a y, Web o Science, EBSCO and Coch ane Lib a y. Only nine s udies me he selec ion
c i e ia. S udy bias was analyzed using he Coch ane isk o bias ool. This sys ema ic e iew
p o ocol was egis e ed a he In e na ional P ospec i e Regis e o Sys ema ic Re iews (PROSPERO:
CRD42023401474). Resul s: Only nine s udies abou clinical ials we e included in his e iew
and show a mode a e quali y o e idence. Me abolomics-based in e en ions ela ed wi h disease
ou come we e con lic i e wi h no o small changes in he me abolic cha ac e is ics o he di e en
cance ypes. Conclusions: This sys ema ic e iew shows some in e es ing esul s ela ed wi h
me abolomics-based in e en ions and hei e ec s on changes in ce ain cance oncome aboli es. The
small numbe o s udies we iden i ied which ul illed ou inclusion c i e ia in his sys ema ic e iew
does no allow us o d aw de ini i e conclusions. Ne e heless, some esul s can be conside ed as
p omising al hough u he esea ch is needed. Tha esea ch mus ocus no only on he p esence o
possible oncome aboli es bu also on possible me abolomics-based in e en ions and hei in luence
on he ou come in pa ien s su e ing om b eas cance , p os a e cance o colon cance .
Keywo ds:
me abolomics; me abolome; gene ics; mycobiome; mic obio a; neoplasms; cance pain;
pain and quali y o li e; oncome aboli e
1. In oduc ion
Cance , a public heal h p oblem [
1
], is one o he main causes o mo ali y and mo -
bidi y [
2
]. In Spain, nine million people a e diagnosed wi h cance annually [
3
] making
Cance s 2023,15, 4297. h ps://doi.o g/10.3390/cance s15174297 h ps://www.mdpi.com/jou nal/cance s
Cance s 2023,15, 4297 2 o 16
i he second leading cause o dea h in Spain [
2
], whe eas i is he leading cause o dea h
wo ldwide [
4
]. Cance is a mul i ac o ial illness, p oduced by en i onmen al, occupa ional,
social, and li es yle ac o s and hei in e ac ion wi h gene ics and he cell me abolism [
2
].
O en less ecognized, he conside a ion o psychological and social aspec s as possible
isk ac o s and hei comp ehensi e and mul idisciplina y managemen is becoming in-
c easingly impo an [
5
]. Con empo a y cance ea men is s ill e y much based on
he use o chemo he apeu ic agen s and mo e ecen ly on immune modula o s [
4
]. The
success o hese he apies is mos ly ela ed o an inc eased li e expec ancy bu o en wi h
he bu den on he quali y o li e [
3
]. Cu en he apies a e mos ly ‘one a ge ’ in e en ions
ha unde es ima e he complexi y o cance as a sys emic disease caused by long- e m
i i a ing li es yle ac o s leading o a s a e o low-g ade in lamma ion, also possibly caused
by he aging p ocess and possible (sub) clinical in ec ions, opposi e o he s ill p e ailing
opinion ha cance is a gene ic disease [6].
Li es yle ac o s such as an inadequa e die o e a p olonged pe iod, excessi e alcohol
consump ion, physical inac i i y, and being o e weigh seem o p oduce mo e han 20% o
mos cance cases and he e o e cance p e en ion p og ams should include li es yle modi-
ica ions [
7
]. Fo example, equen engagemen in physical ac i i y can al eady s ongly
educe he isk o de eloping b eas , colon, endome ial, bladde , s omach, esophageal,
kidney, and p os a e cance [8] and many o hem a e he mos equen ones [9].
Wisha [
10
] comp ehensibly desc ibes he impac o mode n li e isk ac o s and
gene ics on he de elopmen o mul iple cance ypes. The ou come, no su p isingly, is
ha 73–80% o all cance ypes a e caused by li es yle, pollu ion, and o he en i onmen al
ac o s and b eas , p os a e and colon cance , he h ee cance ypes in es iga ed in his
e iew, a e no excep ions.
Knowing ha me abolomics as a science is s ill e y young, we op ed o in es iga e
me abolomics o he h ee mos - equen cance ypes, as we expec ed ha he s udy
numbe would be low. The esul sec o shows ha we only could iden i y a ew s udies
e en in hese h ee mos equen cance ypes (b eas , p os a e and colon).
The use o me abolomics as one o ou -omics (genomics, ansc ip omics, p o eomics)
in cance esea ch, a o ds he possibili y o unde s and complex biological sys ems a he
oo o he de elopmen o cance and iden i y he cellula pheno ype belonging o he
di e en ypes o cance [
11
]. The plus alue o he use o me abolomics in cance is he
ac ha i p o ides a di ec ead-ou o he pheno ype ela ed o he speci ic cell ype in
di e en ypes o cance . Me abolomics, when used in he igh way, shows he sum o
dis o ions a p o ein, DNA, RNA le els and he way cells ha e al e ed hei me abolism
p o iding knowledge abou speci ic oncome aboli es [12,13].
As cance is conside ed mo e and mo e a me abolic disease caused by mul iple
isk ac o s as pa o he ac ual An h opocene, i seems logical o include he science
o me abolomics in de ec ing new a ge s o he ea men and p e en ion o cance in
mo e- o less-suscep ible people, which is he ocus o ou sys ema ic e iew. Ne e ha e
humans been exposed o so many ‘new’ challenges, such as mul iple oxic chemicals, ood
abundancy, si ing ime, and many o he s. I seems logical ha all hose new isk ac o s
a ec gene ics and immunological, endoc inological and me abolic pa hways, measu able
wi h he science o me abolomics [11,14,15].
Some s udies al eady men ion he possible oncome aboli es ela ed o he de elopmen
o he h ee mos equen cance ypes, being b eas , colon and p os a e cance .
Polyamines play a possible ole as oncome aboli es in b eas cance . B eas cance
is he mos common malignancy among women wo ldwide [
16
,
17
]. Ea ly de ec ion and
ad ances in cance ea men ha e a es ed o a 10-yea su i al a e in 80% o women wi h
b eas cance [
17
]. Polyamines ha e been associa ed wi h apid umo g ow h h ough
biosyn hesis and accumula ion in di e en issues. The accumula ion o polyamines has
been e idenced by inc eased plasma and u ine concen a ions o polyamines such as
spe mine and spe midine in b eas cance pa ien s [18,19].
Cance s 2023,15, 4297 3 o 16
In p os a e cance , PSA (p os a e-speci ic an igen) emains he mos in es iga ed
p o ein. P os a e cance is mo e common in men o e 70 yea s o age [
20
], wi h aging
being he mos signi ican isk ac o [
21
]. The de elopmen o p os a e cance is a complex
and sys emic p ocess and scien i ic e idence indica es ha mul iple exogenous ac o s
a ec he p og ession o he disease [
22
], causing p os a e cance in one o e e y eigh men
wo ldwide [
21
]. The incidence o men su e ing om p os a e cance s ill inc eases in mos
de eloped coun ies [
23
] whe eas a end o inc eased li e expec ancy is also obse ed [
24
].
A ecen s udy [
25
] quan i ies he impac o se e al isk ac o s on he de elopmen o
p os a e cance in 41830 Eu opean Ame icans (EAs) and 1282 A ican Ame icans (AAs)
as pa o he P os a e, Lung, Colo ec al, and O a ian Cance Sc eening T ial (PLCO)
p ojec . The ou come was ha he op six isk ac o s ank as ollows, using PSA as p ima y
bioma ke [
25
]: age > PCa- h ( amily his o y o p os a e cance ) > diabe es
≥
ace > li es yle
(smoking and co ee consump ion)
≥
ma i al s a us
≥
BMI > X, in which X ep esen ed a
speci ic die nu ien /ing edien me ic.
O he di e en and e y use ul ac o s in he de elopmen o in e en ions e-
ga ding oncome aboli es ela ed wi h p os a e cance a e choline [
26
], glucose [
10
],
ni ic oxide [
27
] and u ic acid [
28
]. Al hough hese oncome aboli es seem ela ed wi h
he se e i y and mo ali y in pa ien s su e ing om p os a e cance , in e en ions
educing he p esence o o ins ance u ic acid do no show a signi ican educ ion in
umo g ow h o o e all su i al [
29
]. These esul s show he di icul y in unde s and-
ing he way cance cells use oncome aboli es o p oli e a e and p og ess, making he
in e p e a ion o me abolomics essen ial.
Al hough new oncome aboli es ha e been ound in pa ien s su e ing om p os a e
cance , PSA, as a speci ic oncome aboli e, is s ill used as he p ima y bioma ke o he
de ec ion and diagnosis o p os a e cance [22].
Colo ec al cance is he hi d mos -p e alen cance and one o he leading causes
o dea h wo ldwide [
14
,
30
]. Despi e his, he su i al a e is high i i is de ec ed and
ea ed in i s ea ly s ages [
31
]. The incidence o colo ec al cance inc eases wi h age, wi h
mos cases being diagnosed a e age 50. Nine y pe cen o cases a e conside ed spo adic
(non-he edi a y) and he es may be he edi a y [
32
]. The mos common symp oms o his
ype o cance a e changes in bowel habi s and he appea ance o blood in he s ool [
32
].
Di e en oncome aboli es in colon cance ha e been iden i ied including me hionine [
33
],
which is a p omising subs ance because o he possibili y o in e ene wi h a me hionine
and yp ophan deple ion die in pa ien s su e ing om colon cance [33].
Many s udies ha e con i med ha an inadequa e die and unheal hy li es yle play an
impo an ole in he de elopmen o colo ec al cance and high me hionine in ake h ough
a ed mea - ich die is an impo an isk ac o o colon cance [34].
Colon cance p og ession seems o be ela ed wi h o he oncome aboli es ha a e pa
o he acyl-CoA syn he ase/s ea oyl-CoA desa u ase (ACSL/SCD) lipid ne wo k [15].
Me abolomics is pa o omics sciences, [
35
] and has been used o he disco e y o
umo bioma ke s in ecen yea s [
30
]. I can be conside ed as an accu a e, cohe en , and
quan i a i e me hod o examining mul iple mechanisms ela ed o cell g ow h, me abolism,
apop osis and possible cance de elopmen o compa e hose ou comes wi h no mal
unc ioning o cells [
36
]. Me abolomics measu emen s a e pe o med in u ine, se um and
less equen ly in ecal ex ac s, sali a and amnio ic luid [
36
]. Due o he high sensi i i y
o his echnique, unusual changes in he me abolome can be iden i ied a an ea ly s age o
many diseases, including cance , and allow o ea ly diagnosis [
37
]. The ac ual s a e-o - he-
a ela ed o he science o me abolomics jus i ies i s use as a me hod o iden i ying new
cance bioma ke s and oncome aboli es, and he subsequen de elopmen o cance -speci ic
oncome aboli e-di ec ed in e en ions and pe sonalized medicine [
38
,
39
]. The aim o ou
sys ema ic e iew is o add knowledge o he me abolomics o he mos - equen cance
ypes and o o e new ea men op ions o people su e ing om his de as a ing disease.
Cance s 2023,15, 4297 4 o 16
2. Ma e ials and Me hods
2.1. S udy Design
A sys ema ic e iew was conduc ed ollowing he ecommenda ions o he P e e ed
Repo ing I ems o Sys ema ic Re iew and Me a-Analysis (PRISMA) [
40
], which includes
only andomized con olled ials. The p ocess was ca ied ou using he PICOS s a egy.
The p o ocol o his e iew was egis e ed in he In e na ional Regis e o Sys ema ic
Re iews (P ospe ous CRD42023401474). The pu pose o ou e iew and s udy was o
ind scien i ic e idence on b eas , p os a e and colon cance me abolomics, de ec possible
in e en ions ha di ec ly in luence essen ial oncome aboli es and he ou come o disease,
using hose in e en ions.
2.2. Documen a y Sou ces Consul ed
Sou ces used o he manusc ip sea ch we e PubMed, Scopus, Vi ual Heal h Lib a y
(VHL), Coch ane Lib a y and he Web o Science.
2.3. Sea ch S a egy
Keywo ds used and ex ac ed om hesau us Medical Subjec Headings (MesH) we e:
“Me abolomics”, “me abolome”, “gene ics”, “mycobiome”, “mic obio a”, “neoplasms”,
“cance pain”, “pain” and “quali y o li e”. The ollowing non-MesH hesau us e ms we e
also used: me aboli es, human gene ics and mic obiome. The e ms we e combined wi h
he Boolean ope a o s AND and OR. The e ms had o appea in he i le, abs ac and
keywo d lis .
The las sea ch was conduc ed on 10 Feb ua y 2023.
In he Supplemen a y Ma e ials, Table S1 shows he sea ch s a egies ha we e used
o he de ailed s udies.
2.4. Inclusion C i e ia
The inclusion c i e ia we e as ollows:
−Human andomized con olled clinical ials published be ween 2016 and 2023.
−The use o English o Spanish language.
−B eas cance , colon cance and p os a e cance .
2.5. Exclusion C i e ia
All ypes o cance o he han b eas cance , p os a e cance o colon cance we e excluded.
2.6. S udy Selec ion P ocess
The Rayyan QCRI p og am [41] was used o he s o age and subsequen emo al o
duplica es o he included s udies. The p ocess o selec ion and iden i ica ion o he s udies
was ca ied ou by means o selec i e eading o he i le and he abs ac . Subsequen ly, a
ull- ex eading o he a icles ha appa en ly me he inclusion c i e ia was ca ied ou by
all au ho s o his sys ema ic e iew.
2.7. Da a Ex ac ion
The PICOS s a egy was used o da a ex ac ion and included he ollowing da a cha -
ac e is ics: au ho , yea o publica ion, place whe e he s udy was conduc ed and he ype o
cance . Addi ionally, da a we e also ex ac ed on sample cha ac e is ics (size, age, sex), cha -
ac e is ics o he in e en ion ( ype o in e en ion, du a ion, me abolomics, and changes in
me aboli es) and main ou comes (assessmen ools; ollow-up and in e en ion ou comes).
2.8. Risk o Bias Measu emen Tool
The isk o bias ool p oposed by he Coch ane Manual o Sys ema ic Re iews o
In e en ions was used o assess he isk o bias o included s udies [
42
]. This ool assesses
se en domains, whe e each domain is e alua ed wi h h ee possibili ies: “high isk” (
−
),
“low isk” (+) and “unclea isk” (?). The domains ha a e used o he de ec ion isk o
Cance s 2023,15, 4297 5 o 16
bias a e: selec ion bias, pe o mance bias, de ec ion bias, a i ion bias, epo ing biases
and inally o he sou ces o bias. All hese domains help o quali y he le el o scien i ic
e idence o he included s udies.
2.9. Quali y o he E idence
The G ading o Recommenda ions, Assessmen s, De elopmen and E alua ion (GRADE)
ool [
43
] was used o assess he quali y o he e idence o he esul s o he included s udies.
This sys em de ines he quali y o he e idence as he deg ee o con idence and he possibil-
i y o es ima e i a ce ain e ec is signi ican enough o make a clinical ecommenda ion.
Assessmen o he quali y o e idence includes he isk o bias, inconsis ency, imp ecision,
publica ion bias, indi ec esul s and o he ac o s.
3. Resul s
3.1. S udy Iden i ica ion and Selec ion P ocess
In he p ocess o iden i ying and selec ing a icles, a o al o 6854 a icles we e loca ed
in he di e en compu e ized da abases. A e he elimina ion o duplica es, he i le and
abs ac o 44 a icles we e ead o assess whe he he selec ed a icles me he inclusion
c i e ia. A o al o nine a icles me hese c i e ia and he ull ex s we e e alua ed.
Finally, a e ull ex eading, he nine p e iously iden i ied s udies [
44
–
52
] we e
included in his sys ema ic e iew and a low diag am o he sea ch s a egy was de eloped
(Figu e 1).
Figu e 1. Flow diag am illus a ing he s udy p ocess.
3.2. Gene al Cha ac e is ics o he Selec ed S udies
The s udies included in his sys ema ic e iew we e andomized con olled s udies
as a basic condi ion o his sys ema ic e iew [
44
–
52
]. The publica ion pe iod o hese
nine s udies spanned om 2019 o 2021, wi h 2021 [
46
–
49
] being he yea wi h he highes
numbe o he included a icles. Mos included s udies we e published e y ecen ly, and
his highligh s he use o me abolomics as a con empo a y science in medicine.
O he nine s udies, wo we e conduc ed in he Uni ed S a es [
46
,
51
], wo in Spain [
45
,
52
],
one in F ance [
49
], one in I aly [
44
], one in China [
47
], one in Japan [
50
] and he emaining
a icle in Swi ze land [48].
The sum o he sample size o he nine included s udies b ings oge he a o al o
280 indi iduals. The e we e no ad e se e ec s epo ed ela ed wi h he in e en ions ha
we e used o a ge se e al oncome aboli es ound in di e en ypes o cance .

Cance s 2023,15, 4297 6 o 16
In ela ion o gende , he s udy popula ion is made up o men and women. The
pa ien s in he s udies, who su e om b eas cance , p os a e cance o colon cance , a e
all 45 yea s old o olde .
The ollowing able (Table 1) shows he cha ac e is ics men ioned in he s udies.
Table 1. Cha ac e is ics o he included s udies.
Au ho Yea Coun y Cance Sample Gende Age (Yea s)
Pie i e al. [44] 2019 I aly B eas Cance N = 18 Female 74
Á ila-Gal ez e al. [45]2019 Spain B eas Cance N = 27 Female 19
Female 8 (CG) 56 ±10
Chi e al. [46] 2020 USA P os a e Cance N = 40 Male -
Qu e al. [47] 2021 China P os a e Cance N = 32 Male 64 (57–75)
Lee e al. [48] 2021 Swi ze land B eas Cance N = 29 Female -
Feb ey-Combes e al. [49] 2021 F ance B eas Cance N = 58 Female 53.8
Hanada e al. [50]. 2021 Japan Colon Cance
N=8 Male/ emale
4/4 64.0
N=9 Male/Female
6/3
Za ei e al. [51] 2021 USA Colo ec al
Cance N = 20 Male
Female -
Á ila-Gal ez B e al. [52]2021 Spain B eas Cance N = 39 Female 55 ±14
3.3. Risk o Bias in he Included S udies
The assessmen o isk o bias in all he a icles in he s udies was high in mos ields.
Blinding o pa icipan s and pe sonnel and he con olled blinding o e alua o s
indica ed a high isk o bias in he a icles by Pie i e al. and Lee e al. [44,48].
Table 2shows he isk o bias o he included s udies. The di e en colo s ha appea
in he able p esen he me hodological quali y o he s udies: unclea isk (yellow) and low
isk o bias (g een).
Table 2. Risk o bias.
Pie i e al. [44]
Á ila-Gál ez A e al. [45]
Chi e al. [46]
Qu e al. [47]
Lee e al. [48]
Combes e al. [49]
Hanada e al. [50]
Za ei e al. [51]
Á ila-Gál ez e al. [52]
P ope sequence gene a ion
(selec ion isk) +++++++++
Selec ion hiding (selec ion bias) + + + + + + + + +
Blinding o pa icipan s and s a
(implemen a ion bias) +++++++++
Blinding o ou come e alua o s
(de ec ion bias) −+ + + −+ + + +
Incomple e esul s da a
(wea bias) −+ + + −+ + + ?
Selec i e epo ing o esul s
(no i ica ion bias) +++++++++
O he sou ces o bias ? ? ? ? ? ? ? ? ?
Abb e ia ions: (+): low bias isk (−): high bias isk (?): unknown bias isk.
Cance s 2023,15, 4297 7 o 16
3.4. In e en ion Cha ac e is ics
All he s udies show a s udy design including an in e en ion and a con ol g oup o
in es iga e he esponse on an oncome aboli e a ge ing in e en ion in pa ien s su e ing
om b eas , colon o p os a e cance . In h ee s udies [
44
,
47
,
48
] he in e en ion was
pha macological, while in one s udy he e ec s o a medicinal he b we e s udied in people
su e ing om colon cance [
50
], whe eas ano he s udy in es iga ed he impac o an
ae obic exe cise p og am in women wi h b eas cance [
49
] and inally he emaining ou
s udies used di e en die a y s a egies [45,46,51,52].
All s udies esea ched he impac o he in e en ion on di e en oncome aboli es
h ough me abolics es ing in plasma o u ine be o e and a e he in e en ion.
(1)
Pie i e al. [
44
] s udied he e ec s o DHEA in ake, 100 mg/day o ally on pos -
menopausal pa ien s wi h b eas cance wi h he main ou come sa e y. The du a ion
o ea men was 8 weeks and an in e en ion and a con ol g oup we e included.
(2)
Á ila-Gál ez A e al. [
45
] s udied he impac o a mul i-nu ien supplemen on
women wi h b eas cance a e biopsy-con i med diagnosis o su ge y. Nine een
b eas cance pa ien s consumed h ee capsules daily whe eas he con ol g oup
(n = 8)
did no ecei e any addi ional ea men . The mul i-nu ien capsules con ained
pomeg ana e, o ange, lemon, oli e ex ac s, cocoa and g ape seed.
(3)
Chi e al. [
46
] s udied he me abolomic changes in a low-ca bohyd a e die in con-
junc ion wi h and ogen dep i a ion he apy. Fas ing blood samples we e aken o
he con ol o glucose, insulin, p o ein C, lipids, e c., and hese samples we e used
o me abolomic analysis. Ele en pa icipan s in he in e en ion g oup inalized he
s udy (11/20), whe eas 18 in he con ol g oup also inalized he s udy (18/20).
(4) Qu e al. [
47
] s udied he e ec s o he combined applica ion o neoadju an doce axel
and and ogen dep i a ion he apy in people wi h p os a e cance . The pu pose o his
s udy was o in es iga e, wi h he use o me abolomics, he di e ence in endogenous
umo me abolism in p os a e cance pa ien s who ecei ed o did no ecei e neoadju-
an he apy. The coho consis ed o 42 pa ien s ecei ing he combined neoadju an
he apy be o e adical p os a ec omy whe eas 54 pa ien s in he con ol g oup we e
ope a ed on wi hou addi ional in e en ion nex o he adical p os a ec omy.
(5) Lee e al. [
48
] s udied he me abolic e ec s o in a enous selenium injec ions in b eas
cance pa ien s. A placebo (n = 14) and an expe imen al g oup (n = 15) we e included
in he s udy design.
(6)
Feb ey-Combes e al. [
49
] s udied he e ec s on me abolomics o an ae obic exe cise
p og am in b eas cance pa ien s. A six-mon h long combined p og am including
ae obic exe cise and nu i ional changes we e added o he cu en chemo he apy
ea men in women (n = 40) wi h b eas cance , whe eas he con ol g oup (n = 18)
only ecei ed chemo he apy.
(7)
Hanada e al. [
50
] s udied he e ec s o a Chinese he bal medicine, Daikenchu o, on
he me aboli es o pa ien s wi h colon cance a e a le -sided lapa oscopic colec omy.
Nine pa ien s ecei ed he he bal medicine o 6 mon hs whe eas he con ol g oup
did no ecei e any addi ional ea men o he colec omy.
(8) Za ei e al. [
51
] s udied he e ec s o bean in ake on me abolomics measu ed in plasma
and u ine o obese and o e weigh colo ec al cance su i o s. Plasma and u ine
samples we e collec ed a baseline, 2 weeks and 4 weeks a e consump ion. The
s udy included an in e en ion g oup and a placebo meal- ecei ing g oup o in o al
20 pa icipan s.
(9)
Á ila-Gál ez B e al. [
52
] s udied he p esence o iso la ones, cu cuminoids and
lignans (polyphenols) in he issue o people wi h b eas cance a e he in ake o h ee
capsules daily, con aining he a o emen ioned subs ances daily. The me abolic p o iles
o hese polyphenols in no mal and malignan b eas issue in newly diagnosed
b eas cance pa ien s and he an icance ac i i y o me aboli es p oduced in issues
we e e alua ed. The pa ien s we e andomized in o wo g oups; he pa ien s o
he expe imen al g oup consumed h ee capsules daily un il he day o su ge y.
Cance s 2023,15, 4297 8 o 16
The con ol g oup did no ecei e any ype o supplemen a ion be o e hey we e
ope a ed on.
Table 3shows he in e en ion cha ac e is ics in de ail.
Table 3. In e en ion cha ac e is ics.
Au ho Yea Type o
In e en ion Dosage In e en ion
Du a ion o he
In e en ion
(Weeks)
Changes
(Weeks) Me abolomics Me aboli e Changes
Pie i e al.
[44]2019 And ogen
dep i a ion he apy
DHEA 100
mg/day GE = 12 GC = 6 8 8 Plasma No changes obse ed
Á ila
gal ez A
e al. [45]
2019
Capsules
pomeg ana e,
o ange, lemon,
oli e, cocoa and
g ape seed ex ac s.
Th ee
capsules
daily
GE
N = 19
GC
N=8 9 1–2
U ine, plasma,
no mal and
malignan
issue
2,5-dihyd oxybenzoic
acid,
2,6-dihyd oxybenzoic
acid. u oli hin-a
3-o-glucu onide
Chi e al.
[46]2020
Ex eme
low-ca bohyd a e
die (LCD) +
And ogen
dep i a ion he apy
No
speci ied
GE
N = 19
GC
N = 21 24 12–24 Plasma
Dihyd oxycholes anoyl
au ine, dodecanedioic
acid, eicosa e aenoic
acid, palmi oylca ni ine,
oleoylca ni ine,
2-Aminoadipic acid,
malonylca ni ine,
oc anoyla ni ine,
hexanoylca ni ine,
my is oylca ni ine,
decanoylca ni ine,
hep anoyca ni ine,
dodecanoylca ni ine,
and os e one sul a e, hy-
d oxymy is oylca ni ine,
palmi elaidic acid,
3-hyd oxybu yc acid
Qu e al.
[47]2021
Neoadju an
doce axel +
And ogen
dep i a ion he apy
doce axel
(75 mg/m2)
e e y
3 weeks
GE
N = 12
GC
N = 10 24 12–24 umo al issue
Ci a e, succinic acid,
glu amine, GSSG,
adenine, glyce ol
3-phospha e, PC, PE,
LPE, GSH, PS, u idine
Lee e al.
[48]2021 Sodium Seleni e
Injec ion
500 µg
sodium
seleni e, i e
imes o e
2 weeks.
GE
N = 15
GC
N = 14 2 2 Plasma
Co isone, LTB4-DMA y
PGE3, ele a ed in he
expe imen al g oup
Feb ey-
Combes
e al. [49]
2021 Ae obic exe cise
and die a y ad ice
exe cise
sessions
2–3 imes a
week
supe ised
by a aine .
GE
N = 40
GC
N = 18 24
No
changes
ob-
se ed
Plasma No changes obse ed
Hanada
e al. [50]2021 He bal medicine
Daikenchu o
DKT (5 g)
o ally h ee
imes daily
GE
N=8
GC
N=9 4 4 Plasma and
aeces
Dec ease in a achidonic
acid, se a ia and
bilophila.
Za ei e al.
[51]2021 Die a y Na y Bean
In ake
35 g o bean
powde /day GE:10 GC =
10 4 4 Plasma and
u ine
2,3-dihid oxi-2-
me ilbu i a o
S-me hylcys eine,
plasma pipecola e,
u ina y S-
adenosylhomocys eine
Á ila-
Gal ez B
e al. [52]
2021 Cu cumin capsules
Th ee cap-
sules/day
(ex ac s o
u me ic, ed
clo e and
laxseed plus
es e a ol;
296.4 mg
pheno-
lics/capsule;
296.4 mg
pheno-
lics/capsule)
GE
N = 26
GC
N = 13
F om diagnosis o
su ge y 1–2
Plasma, u ine,
malignan
issue, no mal
issue
40-O-glucu onide,
deme hoxycu cumin
cu cumin, es e a ol
3-O-glucu onide,
dihyd o es e a ol
3-O-glucu onide,
es e a ol 3-O-sul a e,
and es e a ol
3-O-sul a e.
Abb e ia ions: GE: expe imen al g oup, GC: con ol g oup; DHEA: Dehyd oepiand os e one; mg: milig am;
m
2
: squa e me e ; GSSG: glu a hione sul ide; PC: ele a ed phosphocholine; PE: Phospha idyle hanolamine; LPE:
lysophospha idyle hanolamine; GSH: Glu a ion; PS: Phospha idylse ine;
µ
g: mic og am; LTB4: Leuko iene B4;
DMA: Dodecanamide; PGE3: P os aglandin E3; DKT: Daikenchu o; g: g am.
Cance s 2023,15, 4297 9 o 16
3.5. Resul s o Oncome aboli e Ta ge ing In e en ions
This sys ema ic e iew consis s o nine andomized con olled ials wi h g ea dispa -
i y ega ding he esul s o oncome aboli e a ge ing in e en ions. The esul s ha e been
di ided acco ding o he ype o cance examined and a e as ollows:
1.
B eas cance : i e s udies esea ched me abolomic changes in b eas cance (Table 4).
(a)
Pie i e al. [
44
]: no clea changes we e obse ed in me aboli es du ing he
8 weeks o ea men ; he au ho s indica e ha his may be due o he small
sample size.
(b)
Á ila-Gál ez A e al. [
45
]: some changes we e de ec ed in he ollowing on-
come aboli es a e he in e en ion we e u oli hin A-3-O-glucu onide, 2,5-
dihyd oxybenzoic acid and es e a ol-3-O-sul a e.
(c)
Lee e al. [
48
]: in his s udy, he le els o co icos e one, LTB4-DMA and PGE3,
which a e an i-in lamma o y compounds, we e ound o be signi ican ly highe
in he expe imen al g oup compa ed wi h he con ol g oup.
(d)
Feb ey-Combes e al. [
49
]: a e 6 mon hs o in e en ion, no me abolomic
changes we e obse ed be ween he subjec s who engaged in he expe i-
men al g oup and hose in he con ol g oup. In lamma o y bioma ke s in-
c eased sligh ly in bo h g oups bu no signi ican di e ences we e obse ed
be ween g oups.
(e)
Á ila-Gál ez B e al. [
52
]: in he expe imen al g oup, high concen a ions o
cu cumin we e p esen in mamma y issues. The use o cu cumin could o e
long- e m an icance e ec s.
2. P os a e cance (Table 5):
(a)
The s udy by Chi e al. [
46
] in he expe imen al g oup comp ised a combina ion
o a die a y in e en ion along wi h and ogen dep i a ion he apy. Se e al
changes we e ound in he expe imen al g oup such as a dec ease in s e oid
syn hesis, and a educ ion in and ogen le els, which we e associa ed wi h
highe se um glucose le els. In addi ion, 3-hyd oxybu y ic acid and ke oge-
nesis dec eased, and acyl-ca ni ines and 3- o myl-indole we e educed wi h
hese changes being associa ed wi h and ogen dep i a ion he apy.
(b)
The s udy by Qu e al. [
47
] in es iga ed a combined neoadju an he apy wi h
and ogen dep i a ion he apy (expe imen al g oup) e sus and ogen dep i-
a ion he apy only (con ol g oup). Nucleo ide syn hesis, lipids, ci ic acid,
and glu a hione me abolism we e all bene icially changed a e he combined
ea men in p os a e cance pa ien s compa ed wi h he con ol g oup.
3. Colon cance —colo ec al (Table 6):
(a)
Hanada e al. [
50
]: me abolome and gu mic obiome analyses showed ha
he le els o plasma lipid media o s associa ed wi h he p o-in lamma o y
a achidonic acid cascade we e lowe in he expe imen al g oup han in he
con ol g oup, which suspec s a educ ion in in lamma o y ac i i y in hose
pa ien s using Daikenchu o as a complemen a y in e en ion.
(b)
Za ei e al. [
51
]: he ollowing me aboli es which all ha e p o ec i e ac ions
agains cance showed an inc ease in he expe imen al g oup only: (i) 2,3-
dihyd oxy-2-me hylbu y a e, (ii) S-me hylcys eine and pipecola e in plasma
and (iii) S-adenosylhomocys eine and (i ) cys eine in u ine. These p omising
esul s jus i y u he s udies o he e ec s nu i ional in e en ions in peo-
ple su e ing om colon cance and a p ima y in e en ion s udy could also
be conduc ed.
Cance s 2023,15, 4297 16 o 16
66.
Han, S.; Gao, J.; Zhou, Q.; Liu, S.; Wen, C.; Yang, X. Role o in es inal lo a in colo ec al cance om he me aboli e pe spec i e: A
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Bischo -Fe a i, H.A.; Wille , W.C.; Manson, J.E.; Dawson-Hughes, B.; Manz, M.G.; Theile , R.; B aendle, K.; Vellas, B.; Rizzoli, R.;
K essig, R.W.; e al. Combined Vi amin D, Omega-3 Fa y Acids, and a Simple Home Exe cise P og am May Reduce Cance Risk
Among Ac i e Adul s Aged 70 and Olde : A Randomized Clinical T ial. F on . Aging 2022,3, 852643. [C ossRe ]
Disclaime /Publishe ’s No e:
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