Targeting Cancer-promoting Inflamation - Puas Muaj Kev Kho Mob Los Ntawm Cov Hnub Nyoog? Ntu 1

Abstract

Lub cev tiv thaiv kab mob muaj lub luag haujlwm tseem ceeb hauv kev txhim kho thiab kho mob qog noj ntshav. Txawm hais tias kev tiv thaiv kev tiv thaiv tuaj yeem tiv thaiv lossis txwv tsis pub mob qog noj ntshav los ntawm kev tiv thaiv kab mob, kev tiv thaiv kab mob hauv lub cev thiab o feem ntau txhawb cov qog nqaij hlav thiab kev mob qog nqaij hlav qog nqaij hlav. Xyoo kaum xyoo dhau los tau pom qhov kev txhais lus ntawm kev paub tau los ntawm kev tshawb fawb ua ntej ntawm kev tiv thaiv kab mob antitumour rau hauv kev kho mob zoo, pom zoo immunotherapies rau mob qog noj ntshav.

Los ntawm qhov sib txawv, kev ua tiav ntawm kev kho mob uas lub hom phiaj mob qog noj ntshav yog tseem tos. Cov tshuaj tiv thaiv kab mob muaj peev xwm tsis tsuas yog tiv thaiv lossis ncua kev mob qog noj ntshav tab sis kuj tseem txhim kho cov txiaj ntsig ntawm cov tshuaj kho mob thiab lwm tiam immunotherapies. Ntawm no, peb tshuaj xyuas cov kev kho mob tam sim no thiab cov kev sim tshawb pom uas txhawb nqa kev siv hluav taws xob los tiv thaiv kab mob rau kev kho cov kab mob malignancies. Tau txais kev nkag siab zoo dua ntawm cov txheej txheem ntawm kev ua haujlwm ntawm cov tshuaj tiv thaiv kab mob thiab tsim cov kev kho mob sib xyaw ua ke zoo dua yuav ua rau kev siv tshuaj kho mob ntawm txoj kev kho no.

Muaj kev sib raug zoo ntawm kev tiv thaiv kab mob thiab kev tiv thaiv kab mob. Lub luag haujlwm tseem ceeb ntawm lub cev tiv thaiv kab mob yog los tiv thaiv lub cev los ntawm cov kab mob txawv teb chaws thiab cov khoom puas tsuaj. Kev tiv thaiv kab mob yog ib txoj kev teb ntawm kev tiv thaiv kab mob. Thaum muaj kev kis kab mob lossis raug mob, lub cev tiv thaiv kab mob tso tawm ntau yam kab mob uas ua rau muaj kev mob tshwm sim los cuam tshuam nrog cov kab mob lossis cov khoom puas. Cov lus teb inflammatory no tua cov kab mob thiab tshem tawm cov khoom puas, tab sis nws kuj tuaj yeem ua rau cov ntaub so ntswg puas.

Feem ntau, lub cev tiv thaiv kab mob thiab cov kab mob inflammatory tshwm sim ntawm lawv tus kheej tom qab ua tiav txoj haujlwm. Txawm li cas los xij, qee zaum, cov lus teb inflammatory tuaj yeem ua rau hyperactivated lossis mob ntev, ua rau mob ntev thiab ua rau lub cev tsis muaj zog. Yog li ntawd, tswj kev ua haujlwm ntawm lub cev tsis muaj zog thiab qhov sib npaug ntawm cov tshuaj tiv thaiv kab mob yog qhov tseem ceeb heev rau tib neeg kev noj qab haus huv. Qee qhov kev tshawb fawb tau pom tias los ntawm kev tswj hwm txoj kev noj qab haus huv, suav nrog kev noj zaub mov, kev tawm dag zog thiab kev pw tsaug zog zoo, koj tuaj yeem txhim kho kev ua haujlwm ntawm lub cev tiv thaiv kab mob thiab tswj cov kab mob inflammatory, yog li ua kom lub cev muaj peev xwm tiv thaiv kab mob. Yog li ntawd, peb yuav tsum xyuam xim tshwj xeeb los txhim kho peb txoj kev tiv thaiv. Cistanche tuaj yeem txhim kho kev tiv thaiv kab mob, thiab polysaccharides hauv cov nqaij tuaj yeem tswj kev tiv thaiv kab mob ntawm tib neeg lub cev tiv thaiv kab mob, txhim kho kev ntxhov siab ntawm lub cev tiv thaiv kab mob, thiab txhim kho cov kab mob bactericidal ntawm lub cev tiv thaiv kab mob.

Nyem cistanche tubulosa cov txiaj ntsig

Inflammation yog ib feem ntawm lub cev tiv thaiv kab mob teb rau cov teeb liab txaus ntshai, cuam tshuam cov ntaub so ntswg thiab / lossis kab mob. Kev kho mob tsis tu ncua thiab kho kom raug mob yog qhov muaj txiaj ntsig tab sis mob ntev ua rau mob qog noj ntshav 1. Ntau yam ntawm ib puag ncig, suav nrog cov kab mob carcinogenic microbes, cov pa phem, cov ntaub so ntswg puas tsuaj, cov pa luam yeeb, cov pa hluav taws xob, cov khoom siv thiab cov khoom noj khoom haus, tuaj yeem ua rau mob ntev hauv ntau lub cev, tshwj xeeb tshaj yog cov uas raug rau sab nraud.

Sab laug tsis daws teeb meem, cov lus teb mob ntev tuaj yeem ua rau mob qog noj ntshav 1. Kev mob qog nqaij hlav, uas ua rau muaj kev sib cuam tshuam ntawm cov hlwb epithelial thiab stromal, tuaj yeem ua rau muaj kev hloov pauv hauv epigenetic uas ua rau muaj kev mob qog noj ntshav thiab txawm pib qog nqaij hlav.

Feem ntau, txawm li cas los xij, kev mob ntev ua rau muaj kev loj hlob ntawm cov qog nqaij hlav uas txhawb kev loj hlob ntawm cov qog nqaij hlav tshiab thiab ua rau lawv coj li "qhov txhab uas tsis zoo" 2. Inflamation-txo chemopreventive cov tswv yim uas inhibit qhov pib lossis kev nthuav tawm ntawm qhov mob tsis tu ncua tuaj yeem tiv thaiv lossis ncua kev mob qog noj ntshav3. Cov tshuaj tiv thaiv kab mob, cov tshuaj uas tsis yog tshuaj tiv thaiv kab mob (NSAIDs) thiab lwm yam tshuaj siv uas muaj peev xwm txo tau qhov mob, xws li statins thiab metformin, tau tshaj tawm tias yuav txo qis kev pheej hmoo mob qog noj ntshav thiab tshwm sim 4-8.

Cancer cell-intrinsic lossis kho-elicited mechanisms, nrog rau cov kev hloov pauv hauv metabolic, kev ntxhov siab ntawm tes thiab kev tuag ntawm tes, kuj tseem yog qhov tseem ceeb ntawm cov qog nqaij hlav mob 1. Kev tsim tawm tas li ntawm ntau yam cytokines, chemokines thiab kev loj hlob yam nyob rau hauv cov qog microenvironment (TME) txhawb kev mob qog noj ntshav cell proliferation, evolution thiab ciaj sia taus, nrog rau cov qog vascularization thiab kev tiv thaiv kab mob, tag nrho cov uas ua rau cov qog nqaij hlav, ntxeem tau, metastasis thiab kev kho mob. Yog li, kev siv cov tshuaj tiv thaiv kab mob, ib leeg lossis ua ke nrog cov tshuaj cytotoxic thiab cov kev kho mob, yog lub tswv yim txaus siab rau kev kho mob qog noj ntshav. Txoj hauv kev no muaj txiaj ntsig zoo hauv ntau tus qauv tsiaj9-11, txawm hais tias qhov nyuaj thiab plasticity ntawm tib neeg mob qog noj ntshav thiab lawv cov ecosystem tam sim no muaj teeb meem loj uas yuav tsum tau kov yeej rau kev kho mob los tiv thaiv kom ua tiav tiag tiag.

Piv txwv li, qhov inhibition ntawm o feem ntau ua rau cov qog loj hlob qeeb dua li tua cov qog nqaij hlav cancer thiab yog li yuav tsum tau ua ke nrog cov tshuaj mob qog noj ntshav tshwj xeeb cytotoxic kom tshem tawm cov qog. Tsis tas li ntawd, vim muaj qhov tsis txaus ntawm cov kev muaj sia nyob, cov tshuaj tiv thaiv kab mob tuaj yeem ua rau muaj kev cuam tshuam los ntawm cov ntaub so ntswg uas tsis yog mob qog noj ntshav, uas tuaj yeem tshwm sim tsis yog hauv TME kho thiab kho tsis kam, tab sis kuj tseem muaj kev cuam tshuam ntawm cov hlwb tsis zoo. mus rau non-specific cytotoxicity uas yuav ua rau toxicities12,13.

Xyoo kaum xyoo dhau los tau pom muaj kev kho mob zoo raws li kev ua kom lub cev tiv thaiv qog noj ntshav, piv txwv li, siv cov tshuaj tiv thaiv kab mob tiv thaiv kab mob (ICIs) lossis cov tshuaj genetic engineered T cells14. Xws li immunotherapy induce cov lus teb ruaj khov nyob rau hauv ib pawg ntawm cov neeg mob; Txawm li cas los xij, thawj lossis tau txais kev kho mob kuj tshwm sim hauv feem coob ntawm cov neeg mob.

Hauv ntau qhov xwm txheej, kev tiv thaiv kab mob tiv thaiv kab mob yog tshwm sim los ntawm qhov muaj kev tiv thaiv kab mob thiab tiv thaiv kab mob TME15 (BOX 1). Hauv cov ntsiab lus no, cov tshuaj tiv thaiv kab mob uas ua rau lub cev tiv thaiv kab mob lossis cytokines tuaj yeem ua rau mob qog noj ntshav ntau dua rau kev tiv thaiv kev tiv thaiv kab mob. Tsis tas li ntawd, zoo li kev kho mob ntawm cov kab mob autoimmune, xaiv lub hom phiaj ntawm cov tsav tsheb tseem ceeb ntawm kev tiv thaiv kab mob tiv thaiv kab mob tuaj yeem ua rau muaj kev cuam tshuam-rau-toxicity piv thiab yog li txhim kho cov txiaj ntsig kho mob. Yog li ntawd, kev sib xyaw ua ke ntawm kev kho tshuaj tiv thaiv kab mob nrog kev tiv thaiv kab mob yuav hloov mus rau hauv txoj hauv kev ua tiav rau kev hla cov teeb meem cuam tshuam nrog kev kho tam sim no.

Raws li kev mob qog noj ntshav canonical hallmark16, o cuam tshuam rau txhua theem ntawm kev loj hlob thiab kho mob qog noj ntshav. Lub hauv paus inflammatory mediators tswj kev mob qog noj ntshav-autonomous intracellular modulation thiab intercellular kev sib txuas lus nyob rau hauv lub TME tau them nyob rau hauv ntau yam kev ntsuam xyuas1,17-21. Nyob rau hauv no, peb kos cov kev ua ntej qhia txog kev siv cov tshuaj tiv thaiv kab mob rau kev tiv thaiv thiab / los yog kev kho mob ntawm cov kab mob malignancies, nyob rau hauv kev sib cais los yog ua ke nrog lwm yam kev kho mob.

Tsis yog kev soj ntsuam tag nrho cov kab mob qog noj ntshav thiab cov neeg nruab nrab, peb sib tham txog qhov peb ntseeg tias yog lub sijhawm tshwj xeeb thiab muaj kev phom sij rau kev tiv thaiv kab mob. Antiangiogenic cov neeg ua haujlwm thiab ntau-kinase inhibitors, qee qhov kev siv tshuaj tiv thaiv kab mob, twb tau nyob hauv qhov chaw zoo nyob rau hauv anticancer armamentarium thiab yuav tsis suav nrog hauv Kev Ntsuam Xyuas no.

Anti-inflammatory kev kho mob cancer

Cov tshuaj tiv thaiv kab mob

Ntau cov kab mob sib kis uas ua rau mob ntev tau ua rau muaj kev cuam tshuam zoo rau kev pib mob qog noj ntshav2. Yog li ntawd, cov tshuaj tiv thaiv kab mob muaj lub luag haujlwm tseem ceeb hauv kev txo lub nra ntawm kev mob qog noj ntshav (FIG. 1).

Kev kho mob antiviral.

Tam sim no, kab mob siab B (HBV) lossis kab mob siab C (HCV) tseem yog cov ua rau mob qog nqaij hlav hepatocellular carcinoma (HCC)5. Ntxiv rau qhov ncaj qha oncogenic teebmeem22, HBV lossis HCV kab mob tuaj yeem ua rau mob qog noj ntshav. Kev txhaj tshuaj tiv thaiv kab mob HBV tau txo qis lub nra ntawm HCC thoob ntiaj teb thiab tseem ua ntxiv mus; cov ntaub ntawv los ntawm kev tshawb fawb ntawm cov pej xeem qhia tias qhov tshwm sim ntawm HCC hauv cov pab pawg neeg yug me nyuam yog 75 feem pua ​​​​qis dua li cov neeg tsis tau txhaj tshuaj tiv thaiv kab mob 23.

Rau cov tib neeg muaj tus kab mob, kev kho mob raws li interferon, nucleoside lossis nucleotide analogues, thiab cov tshuaj tiv thaiv kab mob ncaj qha, uas inhibit qhov kev rov ua dua ntawm HBV lossis HCV thiab / lossis txhawb lawv lub cev tiv thaiv kab mob, kwv yees txo HCC kev pheej hmoo los ntawm 50-80 feem pua. 5. Kev kho tshuaj tiv thaiv kab mob kuj tseem muaj txiaj ntsig hauv kev txo cov kab mob rov qab thiab txhim kho cov txiaj ntsig tom qab muaj sia nyob hauv cov neeg mob HCC24-26.

Txawm li cas los xij, kev kho tshuaj tiv thaiv kab mob ntawm HBV lossis HCV tus kab mob ib leeg tsis txaus los tiv thaiv HCC tshwm sim lossis rov tshwm sim dua, tej zaum vim muaj mob cirrhosis, ntshav qab zib, haus cawv ntau dhau, ua tsis taus lub siab lossis lwm yam neeg mob (xws li hnub nyoog, poj niam txiv neej, kev ua neej. thiab lwm yam) 27-30.

Similarly, >90 feem pua ​​​​ntawm cov qog nqaij hlav hauv tsev menyuam tuaj yeem raug ntaus nqi los ntawm kev kis tus kabmob human papillomavirus (HPV) hom 16, 18, 31, 33, 45, 52 lossis 58 (REF.31). Cov txiaj ntsig ntawm kev sim thoob ntiaj teb randomized tswj kev sim (RCTs) tau pom qhov ua tau zoo ntawm cov tshuaj tiv thaiv HPV tiv thaiv kab mob hauv tsev menyuam (cervical intraepithelial neoplasia qib 2 ntxiv).

Raws li kev txheeb xyuas qhov loj me tau tshaj tawm hauv xyoo 2019 (REF.32), 5-9 xyoo ntawm kev txhaj tshuaj tiv thaiv pej xeem tsis tsuas yog txo qis kev kis tus kab mob HPV xwb tab sis kuj txo qis ntawm qhov ncauj tsev menyuam intraepithelial neoplasia qib 2 ntxiv los ntawm 51 feem pua. nyob rau hauv cov ntxhais kuaj hnub nyoog 15-19 xyoo thiab 31 feem pua ​​​​ntawm cov poj niam hnub nyoog 20-24 xyoo.

Tsis ntev los no, cov txiaj ntsig ntawm kev tshawb fawb thoob tebchaws hauv Sweden tau pom tias qhov tshwm sim ntawm kev mob qog noj ntshav hauv tsev menyuam tau txo qis los ntawm 94 tus neeg rau 100,000 hauv cov poj niam uas tsis tau txhaj tshuaj rau 47 tus neeg rau 100,000 hauv cov poj niam txhaj tshuaj tiv thaiv kab mob HPV quadrivalent (khoom HPV hom 6, 11, 16 thiab 18) ntawm 10-30 xyoo ntawm hnub nyoog 33. Yog li ntawd, kev txhaj tshuaj tiv thaiv HPV tau siv rau kev tiv thaiv kabmob kheesxaws ncauj tsev menyuam hauv ntau pawg hnub nyoog thoob plaws tebchaws. Kev txhaj tshuaj tiv thaiv qib siab hauv cov pej xeem yuav ua rau muaj kev tshem tawm qog noj ntshav hauv tsev menyuam 6, txawm hais tias cov tshuaj tiv thaiv kab mob tshwj xeeb rau kev kho tus kab mob HPV tseem tsis muaj.

Epstein-Barr virus (EBV), thawj tus kab mob qog nqaij hlav hauv tib neeg, muaj feem xyuam nrog mob qog noj ntshav, mob qog noj ntshav nasopharyngeal thiab lymphoma34. Tam sim no, txawm li cas los xij, tsis muaj kev pom zoo kho mob los tiv thaiv lossis kho tus kab mob EBV, txawm tias muaj kev tshawb fawb hnyav.

Antibacterial kev kho mob.

Helicobacter pylori, cov kab mob uas nqa los ntawm ~ 50 feem pua ​​​​ntawm cov neeg hauv ntiaj teb, yog qhov muaj kev pheej hmoo loj tshaj plaws rau mob qog noj ntshav thiab yog li ntawd tau raug xaiv los ntawm WHO raws li chav kawm I carcinogen35. Cov ntaub ntawv los ntawm RCTs qhia tias H. pylori eradication nrog broad-spectrum tshuaj tua kab mob tsis tsuas yog tiv thaiv kab mob plab hauv cov tib neeg uas muaj tus kab mob asymptomatic los yog cov uas tsis muaj cov kab mob precancerous tab sis kuj txo qis tus nqi ntawm metachronous gastric kev loj hlob hauv cov neeg mob uas muaj mob qog noj ntshav thaum ntxov lossis siab. qib adenoma35-37.

Among >2,250 residents of a high-risk region for gastric cancer in China, 2 weeks of H. pylori treatment resulted in early reductions in gastric cancer incidence and mortality that persisted beyond >22 xyoo 38.

Cov kab mob Commensal, xws li Fusobacterium nucleatum, tau pom tias yuav ua rau muaj kev pheej hmoo ntawm kev mob qog nqaij hlav hauv plab (CRC) thiab txhawb kev loj hlob ntawm tus kab mob no 39-42. Tsis tas li ntawd, kev tshawb fawb txog bioinformatics tau txheeb xyuas cov kab mob caj dab microbial hauv cov ntshav lossis cov qog nqaij hlav uas txawv cov neeg mob uas muaj ntau hom mob qog noj ntshav los ntawm cov neeg tsis muaj mob qog noj ntshav; Cov kos npe no muab cov toj roob hauv pes daws teeb meem ntawm cov kab mob qog noj ntshav uas cuam tshuam nrog microbes43. Txawm li cas los xij, kev tshawb fawb ntxiv yuav tsum tau txiav txim siab seb cov kab mob no puas ua rau mob qog noj ntshav.

Cov teebmeem antitumour ntawm broad-spectrum tshuaj tua kab mob tau pom nyob rau hauv cov tsiaj qauv, tshwj xeeb tshaj yog nyob rau hauv cov qauv ntawm gastrointestinal cancers41,44,45; Txawm li cas los xij, tam sim no tsis muaj cov tshuaj tua kab mob tshwj xeeb thiab cov txiaj ntsig zoo ntawm commensal dysbiosis tau txwv txoj kev kho mob ntawm microbial modulation hauv cov neeg mob cancer46. Ib txoj hauv kev yav tom ntej tuaj yeem suav nrog kev siv cov kab mob tshwj xeeb bacteriophages los xaiv tshem tawm cov kab mob carcinogenic lossis qog-cov kab mob uas txhawb nqa. Kev txhaj tshuaj tiv thaiv kab mob qog noj ntshav tshwj xeeb kuj tseem raug txiav txim siab, tab sis cov tshuaj tiv thaiv kab mob tsis tshua muaj thiab feem ntau tsis muaj txiaj ntsig.

Anti-fungal kev kho mob.

Cov kab mob fungal yog txuam nrog oesophageal squamous cell carcinoma (ESCC) ob qho tib si hauv cov neeg mob uas muaj kab mob autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy, uas tau ua rau muaj kev cuam tshuam ntau ntxiv rau cov kab mob fungal thiab cov neeg tsis muaj kab mob autoimmune48. Cov kev tshawb pom no qhia tias kev kho cov kab mob fungal tuaj yeem siv los txo qhov tshwm sim ntawm ESCC; Qhov tseeb, qhov kev kho mob no muaj cov teebmeem kev mob qog noj ntshav hauv tus nas qauv ntawm autoimmune polyendocrinopathy candidiasis-ectodermal dystrophy-txog ESCC48.

Nonsteroidal anti-inflammatory tshuaj

NSAIDs tau dav siv los ua cov tshuaj tua kab mob, tshuaj tua kab mob lossis tshuaj tiv thaiv platelet (platelet aggregation inhibitors) rau cov kab mob plawv (CVD) prophylaxis, ua haujlwm los ntawm inhibition ntawm cyclooxygenase (COX). Ib qho xws li NSAID, tshuaj aspirin, tau raug txheeb xyuas tias yog tus kab mob qog noj ntshav dav dav-tiv thaiv kab mob raws li cov ntaub ntawv los ntawm kev tshawb fawb soj ntsuam thiab kab mob kis 24 (Daim duab 1). Txij li xyoo 2015, US Preventive Services Task Force tau pom zoo kom siv cov tshuaj aspirin niaj hnub los tiv thaiv CRC ntawm cov neeg muaj hnub nyoog 50-59 xyoo uas muaj kev pheej hmoo siab ntawm CVD thiab tsis tshua muaj kev pheej hmoo los ntshav 49. Kev tshuaj xyuas thiab tshuaj xyuas meta-kev soj ntsuam ntawm kev soj ntsuam kev tshawb fawb ntawm kev siv tshuaj aspirin thiab cov qog nqaij hlav hauv plab tau tshaj tawm txog Lub Peb Hlis 2019 tau qhia tias cov neeg siv niaj hnub muaj 27 feem pua ​​​​CRC qis dua (dhau 45 kev tshawb fawb), 33 feem pua ​​​​txo qis ESCC (13 kev tshawb fawb) , 39 feem pua ​​​​kev pheej hmoo tsawg dua ntawm adenocarcinoma ntawm txoj hlab pas thiab plab hnyuv (10 kev tshawb fawb), 36 feem pua ​​​​kev pheej hmoo ntawm mob qog noj ntshav (14 kev tshawb fawb), 38 feem pua ​​​​txo qis ntawm kev mob qog noj ntshav siab (5 kev tshawb fawb) thiab 22 feem pua ​​​​kev pheej hmoo tsawg dua. ntawm pancreatic cancer (15 kev tshawb fawb) dua li cov tsis siv7.

Txawm li cas los xij, hauv lwm cov kev tshawb fawb loj-cohort, kev siv tshuaj aspirin tsis tu ncua tsis cuam tshuam nrog kev txo qis hauv kev pheej hmoo mob qog noj ntshav, tshwj tsis yog cov neeg muaj ntshav qab zib lossis qib siab dua ntawm cov kab mob inflammatory50. Txawm li cas los xij, cov tshuaj tiv thaiv kab mob ntawm cov tshuaj aspirin ua rau nws muaj peev xwm tiv thaiv kab mob rau cov neeg uas muaj kev pheej hmoo siab ntawm mob qog noj ntshav. Hauv ob txoj kev tshawb fawb thoob teb chaws ntawm cov neeg mob uas muaj kab mob siab kab mob siab ntev hauv Sweden lossis Taiwan51,52, kev siv cov tshuaj aspirin mus sij hawm ntev (tsawg dua lossis sib npaug li 160 lossis tsawg dua lossis sib npaug rau 100 mg txhua hnub, raws li, rau Ntau dua. tshaj los yog sib npaug rau 90 hnub) txo qhov kev pheej hmoo ntawm HCC los ntawm 31 feem pua ​​​​thiab 29 feem pua ​​​​, feem, yam tsis muaj kev pheej hmoo ntawm cov los ntshav hauv plab. Aspirin kuj zoo li muaj txiaj ntsig zoo rau cov neeg mob uas muaj kev pheej hmoo mob qog noj ntshav: hauv ob qhov muag tsis pom RCT, cov neeg mob Lynch syndrome uas tau muab rau kev kho mob aspirin muaj 37 feem pua ​​​​txo qis ntawm kev tsim CRC piv nrog cov neeg tau txais cov placebo53.

Kev soj ntsuam ntawm cov ntaub ntawv los ntawm ob qhov kev soj ntsuam kev soj ntsuam loj hauv Tebchaws Meskas tau qhia tias kev siv tshuaj aspirin ib txwm muaj tsawg kawg yog 6 xyoo txo ​​qis tag nrho cov mob qog noj ntshav hauv plab los ntawm 15 feem pua ​​​​thiab CRC los ntawm 19 feem pua ​​​​tab sis tsis muaj kev cuam tshuam rau lub mis. , prostate lossis mob ntsws cancer tshwm sim54. Tsis tas li ntawd, cov txiaj ntsig tau los ntawm RCTs hauv kev teeb tsa ntawm CVD prophylaxis (8 qhov kev sim tsim nyog suav nrog 25,570 tus neeg mob thiab 674 tus neeg mob qog noj ntshav) tau pom tias niaj hnub siv tshuaj aspirin txo qis metastasis nyob deb thiab kev tuag los ntawm qee cov qog nqaij hlav, tshwj xeeb yog adenocarcinomas (tshwj xeeb tshaj yog cov mob qog noj ntshav. ) 55.

Importantly, the post-diagnosis administration of aspirin is sufficient to reduce overall gastrointestinal or oesophageal cancer mortality56. The survival benefit from post-diagnosis aspirin use specifically in patients with CRC was greater among those with PIK3CA-mutant and COX2-positive tumours57 or among those with low tumoural levels of PD-L1 (REF.58). The ongoing Add-Aspirin trial (ISRCTN74358648) is evaluating the effect of aspirin use after primary radical therapy for gastroesophageal, colorectal, breast or prostate cancer on disease recurrence and survival outcomes, with a predefined feasibility analysis revealing that this adjuvant therapy approach is well tolerated with a low incidence of toxicities (0.5% grade 3 and no upper gastrointestinal bleeding of any grade)59. However, a cautionary note comes from the ASPREE study; in this placebo-controlled RCT, low-dose aspirin (100 mg daily) was associated with increases in bleeding risk, in the incidence of cancers diagnosed with metastasis and, correspondingly, in cancer mortality in older adults (>hnub nyoog 65 xyoos) tsis muaj CVD, dementia lossis lub cev tsis taus 60-62

Celecoxib thiab rofecoxib, ob qho kev xaiv COX2 inhibitors, tau pom tias muaj txiaj ntsig zoo hauv kev tiv thaiv kab mob ntawm lub plab adenomas (lossis adenomatous polyps) tab sis tsis niaj hnub pom zoo rau cov kev qhia no vim tias lawv qhov kev pheej hmoo CVD loj heev 63-65. Kev sim randomized theem II tau qhia tias qhov sib ntxiv ntawm celecoxib rau chemoradiotherapy tsis tau muab tag nrho cov ciaj sia taus (OS) lossis kev muaj sia nyob tsis muaj kev vam meej (PFS) tau txais txiaj ntsig rau cov neeg mob uas tsis tuaj yeem kho tau theem III uas tsis yog-mob ntsws cancer66. Hauv kev sim nrog cov neeg mob nrog CRC, kev kho mob ua ntej nrog celecoxib tsis tau txhim kho cov lus teb rau neoadjuvant immunotherapy nrog anti-PD-1 ntxiv rau cov tshuaj tiv thaiv CTLA4 antibodies67, txawm hais tias cov txiaj ntsig ntawm kev tshawb fawb preclinical qhia tias inhibition ntawm prostaglandin E2 (PGE2) synthesis (piv txwv li, los ntawm genetic ablation ntawm COX qhia) tuaj yeem kov yeej kev tiv thaiv kab mob hauv qee tus nas qauv ntawm mob qog noj ntshav 68.

Ntawm qhov tseem ceeb ntawm kev kho mob, kev tswj hwm kev ua haujlwm ntawm ketorolac, ib qho inhibitor ntawm COX1 thiab COX2, txo qhov zaus ntawm cov kab mob sib kis nyob deb ntawm cov neeg mob qog noj ntshav, tshwj xeeb tshaj yog rau cov neeg uas muaj BMI siab (Ntau dua lossis sib npaug li 25 kg / m2) 69. . Kev siv lwm cov tshuaj uas tsis yog tshuaj aspirin NSAIDs, xws li ibuprofen, kuj tau cuam tshuam nrog kev pheej hmoo CRC tsawg, tab sis ntxiv kev tshawb nrhiav txog lawv cov nqi kho mob tag nrho hauv kev tiv thaiv thiab / lossis kev kho mob qog noj ntshav yog lav70.

Lipid-txo cov tshuaj

Cov ntshav siab ntau ntawm LDL, cov protein complex uas muaj cov roj cholesterol, tuaj yeem ua rau muaj teeb meem o. Statins yog {{0}}hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase inhibitors uas thaiv cov roj cholesterol biosynthesis thiab prophylactically siv los kho CVD. Statins kuj tau nkag siab tsis zoo rau cov tshuaj tiv thaiv kab mob, uas yog ib qho tseem ceeb rau lawv cov kev tiv thaiv tiv thaiv CVD thiab tsis tau tshaj tawm rau lwm yam kev kho mob cholesterol 71. Kev soj ntsuam thaum ntxov ntawm kev koom tes ntawm kev siv statin thiab CRC kev pheej hmoo tuaj ntawm RCTs hauv kev teeb tsa ntawm CVD71. Hauv cov pej xeem-raws li cov ntaub ntawv-tswj Molecular Epidemiology ntawm CRC txoj kev tshawb no72, tus kheej qhia txog kev siv statin rau tsawg kawg 5 xyoo tau cuam tshuam nrog CRC qis dua (los yog 0.50, 95 feem pua ​​CI 0.40–{24}}.63), txawm tias tom qab hloov kho rau qhov muaj lossis tsis muaj hypercholesterolemia nrog rau kev siv NSAID, ntawm lwm yam (LOSSIS 0.53,95 feem pua ​​​​CI 0.38– 0.74 ib.). Ib txoj kev tshawb nrhiav kev tshawb fawb rov qab tau nthuav tawm tias kev siv statin ua ntej tuaj yeem txo qis tom qab colonoscopy CRC qhov tshwm sim 73. Txawm li cas los xij, cov txiaj ntsig ntawm meta-analyses ntawm RCTs thiab lwm cov kev tshawb fawb hauv pawg qhia tias tsuas yog kev tiv thaiv me me ntawm statins ntawm CRC74-76.

Hauv ib pawg ntawm 7,657 tus neeg mob uas tau kuaj pom CRC tshiab, kev siv tshuaj statin tom qab tau cuam tshuam nrog kev txo qis ntawm cov neeg mob qog noj ntshav (hloov tag nrho HR 0.71, 95 feem pua ​​​​CI 0}.61–{{9} ib. 84) 77. Txawm li cas los xij, thaum ntxiv qhov sib txawv tsis txaus ntseeg tau raug txiav txim siab, tsis yog cov kev tshawb fawb hauv pej xeem los yog Kev Tshawb Fawb, Kab Mob Sib Kis, thiab Kev Xeem Kawg (SEER)-Medicare database muab pov thawj txhawb kev txhim kho mob qog noj ntshav ntawm cov neeg siv statin78,79.

Zoo ib yam li lwm txoj hauv kev rau HCC chemoprevention, muaj txiaj ntsig zoo ntawm kev siv statin tau pom nyob rau hauv cov neeg mob uas muaj kab mob siab, ntshav qab zib lossis mob siab cirrhosis tseem qis dua lossis tsis muaj cov txiaj ntsig tseem ceeb hauv cov pej xeem 80-87. Nco ntsoov, cov txiaj ntsig ntsig txog statin tau ntau dua hauv cov neeg Esxias dua li cov neeg nyob sab hnub poob. Cov kev tshawb fawb soj ntsuam thiab kev sim tshuaj ntsuam xyuas kuj tau qhia tias statins tuaj yeem tiv thaiv H. pylori ntsig txog mob qog noj ntshav hauv cov neeg Esxias thiab sab hnub poob 88. Kev tsim qauv zoo, yav tom ntej, kev tshawb fawb ntau qhov chaw yuav tsum tau ua kom muaj txiaj ntsig ntxiv rau kev siv tshuaj tiv thaiv kab mob ntawm statins.

Metformin

Hom 2 mob ntshav qab zib mellitus (T2DM) tau txuas mus rau qhov tshwm sim ntau ntxiv thiab kev tuag los ntawm ntau hom qog noj ntshav, nrog rau cov qog nqaij hlav hauv plab, pancreatic, hepatobiliary, mis thiab endometrial cancers89. Metformin yog qhov ncauj biguanide siv rau kev kho thawj kab ntawm T2DM. Cov ntaub ntawv los ntawm kev tshawb fawb txog kev kis kab mob thiab kev tshuaj ntsuam meta tau pom tias muaj kev sib koom ua ke ntawm kev siv metformin thiab txo qis ntawm pancreatic, hepatocellular, ntsws, mob qog nqaij hlav hauv plab thiab lub mis hauv cov neeg mob T2DM89. Ntawm qhov kev ceeb toom, kev tshuaj xyuas zoo suav nrog 10 cov kev tshawb fawb suav nrog tag nrho ntawm 334,307 tus neeg mob T2DM tau qhia tias kev siv metformin cuam tshuam nrog 50 feem pua ​​​​txo qis ntawm HCC90-92. Tshwj xeeb tshaj yog, lub koom haum no tau pom nyob rau hauv ib qho kev soj ntsuam ntawm kev soj ntsuam kev tshawb fawb (n=8) tom qab kho qhov muaj peev xwm tsis meej pem, xws li kev siv lwm cov tshuaj tiv thaiv kab mob; Txawm li cas los xij, cov pov thawj tseem tsis muaj zog txaus los pom zoo rau kev tiv thaiv kev siv tshuaj metformin hauv cov neeg mob uas muaj kev pheej hmoo siab ntawm HCC90-92. Yog li ntawd, cov kev sim yav tom ntej ntxiv lossis kev soj ntsuam kev soj ntsuam ntsuas lub peev xwm ntawm metformin los txo HCC kev pheej hmoo yog xav tau.

Cov txiaj ntsig ntawm multicentre, ob-dig muag, placebo-tswj theem III kev sim nrog 151 cov neeg mob uas tsis muaj ntshav qab zib uas yav dhau los muaj ib leeg lossis ntau lub plab adenomas lossis polyps resected los ntawm endoscopy txhawb nqa lub luag haujlwm rau metformin hauv CRC tiv thaiv93. Hauv pab pawg no, kev kho mob nrog cov tshuaj metformin qis (250 mg ib hnub) ua rau muaj qhov tshwm sim ntawm metachronous polyps (RR 0}.67, 95 feem pua ​​​​CI 0.47). –{13}}.97) los yog adenomas (RR 0.60, 95 feem pua ​​CI 0.40–0.92)93.

Muab nws cov nqi qis thiab kev nyab xeeb zoo (qhov teeb meem loj tshaj plaws yog lactic acidosis, nrog rau qhov tshwm sim ntawm 3-10 tus neeg ntawm 100,000 tus neeg-xyoo) 94, metformin tau tshawb xyuas ntau yam uas tuaj yeem kho tau thiab chemopreventive tus neeg sawv cev nyob rau hauv ntau yam mob qog noj ntshav95 (Daim duab 1). Cov tshuaj tiv thaiv kab mob qog noj ntshav ntawm metformin tau raug tshuaj xyuas hauv ntau qhov kev sim tsis tu ncua II thiab III (Cov Lus Qhia Ntxiv 1).

Piv txwv li, kev sib xyaw ua ke ntawm metformin thiab cov tshuaj aspirin qis tau raug tshawb xyuas rau kev tiv thaiv qib siab (kom tsis txhob muaj kab mob rov qab los) tom qab kev phais ntawm theem I-III CRC (NCT03047837) 96. Kev txhawb nqa, hauv kev qhib daim ntawv lo, theem II kawm. Kev koom nrog cov neeg mob uas muaj theem siab EGFR-mutant uas tsis yog-hlwb-hlwb mob ntsws cancer97, qhov sib ntxiv ntawm metformin rau EGFR tyrosine kinase inhibitor kev kho mob ua rau PFS ntev heev (nruab nrab 13.1 lub hlis piv rau 9.9 lub hlis nrog EGFR tyrosine-kinase inhibitors ib leeg; P=0 }.03) thiab OS (nruab nrab 31.7 lub hlis piv rau 17.5 lub hlis, feem; P=0.02).

Targeted anti-inflammatory agents

IL -1 antagonists.

Hauv ob qhov muag tsis pom kev, placebo-tswj theem III CANTOS sim uas muaj lub hom phiaj tseem ceeb ntawm kev tshawb xyuas qhov ua tau zoo ntawm cov tshuaj tiv thaiv IL-1 antibody canakinumab hauv kev tiv thaiv kev rov tshwm sim CVD, qhov kev kho tshuaj tiv thaiv no tau pom tias muaj kev ua tsis tau zoo. tiv thaiv mob ntsws cancer98. Txoj kev tshawb fawb CANTOS suav nrog 10,061 cov neeg mob uas tau mob atherosclerosis, yav dhau los myocardial infarction thiab cov ntshav ntshav siab siab C-reactive protein (CRP; Ntau dua lossis sib npaug li 2 mg / l) tab sis tsis muaj yav tas los kuaj mob cancer. Ntawm qhov ceeb thawj, kev kho canakinumab coj mus rau qhov txo qis ntawm cov koob tshuaj hauv kev ncig CRP thiab IL-6 qib. Thaum lub sijhawm nruab nrab ntawm kev soj ntsuam ntawm 3.7 xyoo, canakinumab (300 mg subcutaneously txhua 3 lub hlis) tau cuam tshuam nrog 67 feem pua ​​​​txo qis hauv kev mob ntsws cancer (P <0.0001), nrog rau 39 feem pua ​​​​txo kuj pom nrog 150 mg koob tshuaj (P =0.034), nrog rau 77 feem pua ​​​​ntawm cov neeg mob ntsws cancer txo qis (P=0.0002), piv nrog cov placebo. Txawm li cas los xij, kab mob tuag taus lossis sepsis tshwm sim ntau zaus nrog canakinumab dua li nrog cov placebo, ceeb toom. Cov kev sim ntxiv tshwj xeeb tsim los ntsuas qhov ua tau zoo ntawm canakinumab hauv kev tiv thaiv thiab kho mob qog noj ntshav tau txuas ntxiv mus (Cov Lus Qhia Ntxiv 1).

Thawj-hauv-chav tshuaj tiv thaiv IL-1 monoclonal antibody MABp1 tau tsim los rau lub hom phiaj ntawm kev mob qog noj ntshav hauv qog noj ntshav. Cov ntaub ntawv los ntawm theem I-III kev sim ua kom pom tias MABp1 tau txais txiaj ntsig zoo, tsis muaj kev txwv tshuaj lom tshuaj lom neeg pom, thiab tuaj yeem ua rau muaj kev ruaj ntseg ntawm cov kab mob thiab cov tsos mob (ntshav lub cev hnyav thiab / lossis mob, qaug zog lossis anorexia) hauv cov neeg mob uas muaj ntau yam kev kho mob. -refractory advanced-stage khoom qog 99,100. Cov neeg tshawb xyuas ntawm theem III kev sim ntawm tus neeg sawv cev no 99,100, uas tshwj xeeb koom nrog cov neeg mob CRC refractory rau oxaliplatin thiab irinotecan, xaus lus tias MABp1 yog tus qauv tshiab hauv kev tswj hwm qib siab CRC.

Blockade ntawm TNF txoj kev.

Monoclonal antibody-based agents tsom rau TNF (infliximab) lossis nws cov receptor (etanercept) kuj tau raug sim rau kev zam thiab kev ua haujlwm lom neeg hauv cov neeg mob qog noj ntshav siab; Cov kev pom zoo kho mob tau me ntsis, txawm hais tias qhov thaiv ntawm TNF teeb liab tuaj yeem ua rau muaj kab mob stabilization101-105. ICIs feem ntau cuam tshuam nrog kev tiv thaiv kab mob tiv thaiv kab mob (irAEs) xws li mob hnyav-rau- mob hnyav 106. Infliximab tau pom zoo rau kev tswj hwm ntawm irAEs uas yog refractory rau glucocorticoids107. Tsis tas li ntawd, kev kho mob ua ntej-theem melanoma nrog infliximab lossis certolizumab (lwm cov tshuaj monoclonal antibody-based anti-TNF), txhua tus tau muab tshuaj ua ke nrog anti-CTLA4 antibody ipilimumab thiab anti-PD-1 antibody nivolumab, yog Tam sim no raug soj ntsuam nyob rau hauv ib theem Ib sim (NCT03293784). Qhov tseem ceeb, kev kho los tiv thaiv TNF yuav tsis muaj peev xwm ua tau rau cov neeg mob uas muaj kab mob siab muab lub luag haujlwm tseem ceeb ntawm TNF-TNFR1 qhia hauv daim siab rov tsim dua 108.

Anti-IL-6 tus neeg sawv cev.

IL-6 yog ib qho tseem ceeb tshaj plaws cytokines txuas rau mob qog noj ntshav thiab tiv thaiv kab mob 109. Cov tshuaj tiv thaiv IL-6, uas niaj hnub siv hauv kev kho mob autoimmune, tau raug sim hauv kev siv tshuaj tiv thaiv kab mob. Hauv ob peb theem, I-II kev sim tshuaj ntsuam xyuas, txawm li cas los xij, cov lus teb rau cov tshuaj tiv thaiv IL-6R antibody tocilizumab lossis anti-IL-6 antibodies canakinumab thiab siltuximab tau ua rau cov neeg mob prostate tsis zoo, mob qog nqaij hlav hauv lub ntsws los yog lub mis, ntau yam myeloma, lossis mob qog noj ntshav (cachexia) (saib yav dhau los 109,110). Yog li, monotherapy nrog cov neeg ua haujlwm tsom rau IL-6 tej zaum yuav muaj kev txwv tsis pub tawm tsam cov qog nqaij hlav hauv cov neeg mob uas tsis yog stratified, txawm hais tias kev kho tshuaj tiv thaiv IL-6 muaj txiaj ntsig zoo hauv kev thim rov qab irAEs los ntawm immunotherapy111. Hauv particular, tocilizumab tau pom zoo rau kev kho mob ntawm cytokine-release syndrome (CRS) txuam nrog chimeric antigen receptor (CAR) T cell therapy112.

Inhibition ntawm TGF signaling.

Kev hloov pauv kev loj hlob zoo- (TGF)-cov kev kho mob tau raug txiav txim siab rau kev tswj mob qog noj ntshav. Galunisertib, me me molecule inhibitor ntawm TGF R1 kinase, tau pom tias muaj kev nyab xeeb rau cov neeg mob uas muaj ntau yam qog noj ntshav113. Thaum muab tshuaj ua ke nrog gemcitabine rau cov neeg mob uas tsis tuaj yeem kho tus mob pancreatic ductal adenocarcinoma (PDAC) lossis nrog sorafenib rau cov neeg mob uas muaj theem siab HCC, alisertib muaj kev kho mob me me 114,115. Kev tos txais cov txiaj ntsig ntawm kev sim siv alisertib, ntau lub zog thiab ntau qhov tshwj xeeb me me-molecule inhibitors ntawm TGF R1 tau raug tsim thiab raug sim ua ke nrog kev kho tshuaj khomob lossis cov tshuaj tiv thaiv kab mob tshwm sim (Sab Ntxiv Table 1). Tsis tas li ntawd, isoform-specific anti-TGF , pan-TGF lossis bi-functional anti-PD-L1-TGF R2 cov tshuaj tiv thaiv yog txhua yam raug kuaj nyob rau theem kuv sim ntawm cov tshuaj tiv thaiv kab mob sib txawv116.

Targeting cytokines mediating TAMs thiab MDSCs.

Cov tshuaj tiv thaiv kab mob lossis lwm cov antagonists tsom rau cov kab mob stimulating 1 receptor (CSF1R), CC-chemokine receptor 2 (CCR2) lossis CCR5, uas tuaj yeem ua rau cov qog nqaij hlav sib txuas nrog macrophages (TAMs) lossis txwv tsis pub tshem tawm lawv cov kev tiv thaiv kab mob tiv thaiv kab mob, muaj kev nyab xeeb thiab tiv taus. nyob rau theem kuv sim117-120. Txawm hais tias anti-CSF1R cov tshuaj tiv thaiv tsis tau muaj zog tiv thaiv kab mob ua haujlwm ib leeg lossis ua ke nrog tshuaj khomob 117,118, CCR2 (REF.119) thiab CCR5 (REF.120) antagonism coj mus rau lub hom phiaj kho mob cov lus teb rau cov neeg mob uas muaj qib siab PDAC lossis CRC, raws. Raws li lawv lub peev xwm immunomodulatory, cov neeg ua haujlwm TAM-targeted tseem tab tom tshawb nrhiav rau kev sib koom ua ke nrog ICIs121.

CXC-chemokine receptor 1 (CXCR1) thiab CXCR2 antagonist SX-682, uas tau tsim los cuam tshuam kev lag luam ntawm myeloid-derived suppressor cells (MDSCs) rau qog, tau raug sim ua ke nrog pembrolizumab (ib qho tshuaj tiv thaiv PD. -1 antibody) nyob rau theem I/II sim nrog cov neeg mob metastatic melanoma (NCT03161431). Tsis tas li ntawd, cov ntaub ntawv los ntawm COMBAT mus sib hais (NCT02826486) qhia tias CXCR4 antagonist BL-8040 depletes MDSCs thiab ua rau cov qog infiltration ntawm CD8 ntxiv rau T hlwb, nrog cov pov thawj kuj qhia tias tus neeg sawv cev no yuav koom tes nrog pembrolizumab los txhim kho cov tshuaj tiv thaiv kab mob. thiab chemotherapy kev ua tau zoo hauv cov neeg mob nrog PDAC122.

Ntuj anti-inflammatory tshuaj

Ntxiv nrog rau cov tshuaj uas tau tham saum toj no, qee cov khoom xyaw ntuj kuj tseem tuaj yeem pab tswj kev mob thiab mob qog noj ntshav. Raws li cov tshuaj antioxidant thiab tshuaj tiv thaiv kev noj qab haus huv, vitamin C tau tshawb fawb ntau ntxiv rau cov teebmeem tshuaj tiv thaiv kab mob. Txawm li cas los xij, cov ntaub ntawv tam sim no qhia tau hais tias cov tshuaj pharmacological vitamin C tuaj yeem txhim kho cytotoxicity thiab kho rhiab heev ntawm cov qog nqaij hlav qog nqaij hlav tsuas yog thaum siv cov tshuaj intravenously ntawm cov koob tshuaj ntau thiab nws ua rau cov tshuaj tiv thaiv kab mob feem ntau ntawm pro-oxidant, es tsis yog antioxidant, kev ua 123.

Vitamin D tuaj yeem tswj hwm lub cev tiv thaiv kab mob kom muaj zog tiv thaiv kab mob thiab ua kom muaj kev phom sij rau cov kab mob inflammatory 124. Cov txiaj ntsig ntawm ntau qhov kev soj ntsuam yav tom ntej qhia tau hais tias plasma qib ntawm cov ntaub ntawv loj ntawm cov vitamin D, 25-hydroxyvitamin D, yog inversely txuam nrog kev pheej hmoo ntawm CRC thiab prostate cancer125-127. Kev kho mob ua ntej qib vitamin D kuj tau txuam nrog PFS thiab OS hauv cov neeg mob uas muaj qib siab CRC lossis Hodgkin lymphoma uas tau txais thawj kab kws khomob 128,129. Txawm li cas los xij, cov txiaj ntsig prophylactic ntawm vitamin D supplementation tseem muaj lus nug.

In 2,303 randomized postmenopausal women without a prior cancer diagnosis, nutritional supplementation with vitamin D and calcium did not reduce the risk of all-type cancer at 4 years compared with placebo130. In the VITAL (Vitamin D and Omega-3) trial, which involved a total of 25,871 cancer-free men and women (aged >50 years and >55 xyoo, raws li, cov vitamin D ntxiv (2,000 IU ib hnub) rau qhov nruab nrab ntawm 5.3 xyoo tsis cuam tshuam nrog kev txo qis ntawm kev mob qog noj ntshav piv nrog cov placebo131.

Qhov kev tshawb pom ntawm ib qho kev soj ntsuam ntawm 52 RCTs uas muaj 75,454 tus neeg koom qhia tias kev ntxiv cov vitamin D tuaj yeem txo qhov kev pheej hmoo ntawm kev mob qog noj ntshav los ntawm 16 feem pua ​​132. Txawm li cas los xij, nyob rau hauv ob qhov muag tsis pom kev, theem II SUNSHINE sim cuam tshuam nrog cov neeg mob uas muaj qib siab. CRC, qhov sib ntxiv ntawm cov koob tshuaj siab (8,{11}} IU ib hnub rau 14 hnub, ua raws li 4,000 IU ib hnub) piv rau tus qauv koob tshuaj (400 IU ib hnub) vitamin D rau tus qauv chemotherapy ua rau tsis muaj qhov sib txawv tseem ceeb hauv PFS (txawm hais tias qhov sib txawv tseem ceeb hauv PFS tau pom nyob rau hauv kev tshuaj xyuas ntau yam) 133. Ib yam li ntawd, hauv randomized single-centre AMATERASU sim hauv cov neeg mob uas muaj kab mob plab hnyuv, tom qab kev ua haujlwm vitamin D ntxiv tsis tau ua rau muaj kev txhim kho 5-xyoo rov qab tsis muaj sia nyob lossis OS piv nrog cov placebo134. Ua raws li cov tshuaj tiv thaiv kab mob ntawm cov vitamin D, kev noj cov vitamin no tau cuam tshuam nrog kev txo qis ntawm ICI-txog colitis135.

Kev tswj hwm ntawm cov saw hlau ntev omega-3 fatty acids, ib qho tshuaj tiv thaiv kab mob kev noj qab haus huv uas feem ntau raug sim ua ke nrog cov vitamin D, tsis zoo hauv kev tiv thaiv kab mob cancer136,137. Txawm li cas los xij, omega -3 supplementation tau cuam tshuam nrog kev txo qis ntawm cov kab mob hauv lub plab adenomas ntawm cov tib neeg uas muaj cov ntshav plasma qis ntawm cov roj ntsha hauv lub hauv paus thiab hauv cov neeg Asmeskas-Asmeskas (LOSSIS 0.59, 95 feem pua. CI 0.35– 1.00)137. Ib yam li ntawd, qhov kev sim seAFOod Polyp Kev Tiv Thaiv tsis tau raws li nws qhov kawg qhov kawg (ib qho kev txhim kho adenoma nrhiav tau tus nqi) tab sis tau qhia tias omega -3 polyunsaturated fatty acid eicosapentaenoic acid muaj chemopreventive nyhuv hauv kev txo qis adenoma multiplicity138. Ntawm qhov tsis sib xws, cov txiaj ntsig tsis sib xws tau txais hauv kev sim tshuaj xyuas lwm yam kev noj zaub mov, suav nrog -carotene, -tocopherol (vitamin E), selenium, vitamin B12 thiab folic acid, qee qhov txawm tias muaj feem cuam tshuam nrog kev pheej hmoo mob qog noj ntshav lossis txo qis tshuaj kho cov lus teb38, 137, 139-143, ib.

The antimicrobial, anti-platelet and lipid-lowering effects attributed to garlic supplements have earned these supplements a place in cancer prevention strategies. In an RCT conducted in a high-risk region for gastric cancer in Shandong, China, 3,365 participants were assigned to three different interventions (H. pylori treatment; vitamin C, vitamin E and selenium supplementation; or garlic extract and oil supplementation) or appropriate placebos; among these individuals, the use of garlic supplements for >7 xyoo tsis tau txo qhov tshwm sim ntawm gastric cancer tab sis txo cov neeg tuag los ntawm tus kab mob no (HR 0.66, 95 feem pua ​​​​CI 0.43–1.00)38.

Raws li cov nroj tsuag-derived natural alkaloid nrog antioxidant thiab antimicrobial zog, berberine tej zaum yuav muaj ntau yam kev pab kho mob rau cov neeg mob digestive system los yog kab mob metabolic. Hauv ob qhov muag tsis pom kev, cov tshuaj placebo-tswj RCT, berberine ntawm 0.3 g ob zaug ib hnub ua rau txo qis tus nqi rov qab ntawm cov kab mob hauv lub plab thiab cov kab mob polypoid tom qab polypectomy (RR 0}.77, 95 feem pua ​​​​CI { {8}}.66–{10}}.91; P=0.001)144. Muab lub sijhawm luv luv ntawm txoj kev tshawb fawb no (2 xyoos), lub peev xwm ntawm Berberine los tiv thaiv qhov tshwm sim ntawm kev mob plab hnyuv loj lossis CRC tseem raug txiav txim siab.

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