# Cytokines and Chemokines as Emerging Biomarkers and Therapeutic Targets in Colorectal Cancer—Narrative Review **Authors:** Weronika Sokólska, Monika Gudowska-Sawczuk, Karolina Orywal PMC · DOI: 10.3390/ijms27041996 · International Journal of Molecular Sciences · 2026-02-19 ## TL;DR This review explores how cytokines and chemokines could serve as biomarkers and therapeutic targets in colorectal cancer, offering new ways to detect and treat the disease. ## Contribution The paper highlights novel cytokine and chemokine pathways as potential diagnostic and therapeutic tools for personalized colorectal cancer treatment. ## Key findings - Cytokines and chemokines like IL-6, CXCL8, CCL2, and the CXCL12-CXCR4 axis are consistently linked to tumor progression and treatment response in CRC. - Targeting cytokine and chemokine pathways offers emerging therapeutic strategies, including immune checkpoint inhibitors and chemokine signaling modulation. - Combining cytokine-based approaches with conventional therapies may improve treatment outcomes in colorectal cancer. ## Abstract Colorectal cancer (CRC) is a significant global health challenge, characterized by an increasing incidence rate and high mortality rate. Early detection and effective treatment are crucial to improving patients’ quality of life. Cytokines and chemokines are key modulators of the tumor microenvironment, influencing the recruitment of immune cells, angiogenesis, proliferation, and metastasis. This narrative review summarizes the current knowledge regarding the potential diagnostic and therapeutic applications of selected cytokines and chemokines in CRC. We discuss their potential as biomarkers for early detection, prognosis, and prediction of treatment response. We also highlight emerging therapeutic strategies targeting cytokine and chemokine pathways, including immune checkpoint inhibitors, modulation of chemokine signaling, and the direct use of cytokines to enhance antitumor immunity, with particular emphasis on interleukin-6 (IL-6), C-X-C motif chemokine ligand 8 (CXCL8), C-C motif chemokine ligand 2 (CCL2), and the C-X-C motif chemokine ligand 12 (CXCL12)–C-X-C chemokine receptor type 4 (CXCR4) axis, which show consistent associations with tumor stage, metastasis, and treatment response. Integrating cytokine- and chemokine-based approaches with combination therapies could lead to more effective conventional treatments. In summary, this review emphasizes the potential of cytokines and chemokines as diagnostic tools and therapeutic targets, paving the way for more personalized and effective treatment strategies for colorectal cancer. ## Linked entities - **Proteins:** IL6 (interleukin 6), CXCL8 (C-X-C motif chemokine ligand 8), CCL2 (C-C motif chemokine ligand 2), CXCL12 (C-X-C motif chemokine ligand 12), CXCR4 (C-X-C motif chemokine receptor 4) - **Diseases:** colorectal cancer (MONDO:0005575) ## Full-text entities - **Genes:** PIK3CA (phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha) [NCBI Gene 5290] {aka CCM4, CLAPO, CLOVE, CWS5, HMH, MCAP}, MMP2 (matrix metallopeptidase 2) [NCBI Gene 4313] {aka CLG4, CLG4A, MMP-2, MMP-II, MONA, TBE-1}, IL15 (interleukin 15) [NCBI Gene 3600] {aka IL-15}, CD274 (CD274 molecule) [NCBI Gene 29126] {aka ADMIO5, B7-H, B7H1, PD-L1, PDCD1L1, PDCD1LG1}, IL12A (interleukin 12A) [NCBI Gene 3592] {aka CLMF, IL-12A, NFSK, NKSF1, P35}, CXCR4 (C-X-C motif chemokine receptor 4) [NCBI Gene 7852] {aka CD184, D2S201E, FB22, HM89, HSY3RR, LCR1}, PMS2 (PMS1 homolog 2, mismatch repair system component) [NCBI Gene 5395] {aka HNPCC4, LYNCH4, MLH4, MMRCS4, PMS-2, PMSL2}, MYD88 (MYD88 innate immune signal transduction adaptor) [NCBI Gene 4615] {aka IMD68, MYD88D, WM1}, IL2 (interleukin 2) [NCBI Gene 3558] {aka IL-2, TCGF, lymphokine}, PIK3CB (phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit beta) [NCBI Gene 5291] {aka P110BETA, PI3K, PI3KBETA, PIK3C1}, VEGFB (vascular endothelial growth factor B) [NCBI Gene 7423] {aka VEGFL, VRF}, GSK3B (glycogen synthase kinase 3 beta) [NCBI Gene 2932], Il22ra2 (interleukin 22 receptor, alpha 2) [NCBI Gene 237310] {aka CRF2-10, CRF2-s1, CRF2X, Il-22bp}, ERBB2 (erb-b2 receptor tyrosine kinase 2) [NCBI Gene 2064] {aka CD340, HER-2, HER-2/neu, HER2, MLN 19, MLN-19}, CASP3 (caspase 3) [NCBI Gene 836] {aka CPP32, CPP32B, SCA-1}, EBI3 (Epstein-Barr virus induced 3) [NCBI Gene 10148] {aka IL-27B, IL27B, IL35B}, TRAF6 (TNF receptor associated factor 6) [NCBI Gene 7189] {aka MGC:3310, RNF85}, IL12B (interleukin 12B) [NCBI Gene 3593] {aka CLMF, CLMF2, IL-12B, IMD28, IMD29, NKSF}, IL27 (interleukin 27) [NCBI Gene 246778] {aka IL-27, IL-27A, IL27A, IL27p28, IL30, p28}, CD4 (CD4 molecule) [NCBI Gene 920] {aka CD4mut, IMD79, Leu-3, OKT4D, T4}, FLT4 (fms related receptor tyrosine kinase 4) [NCBI Gene 2324] {aka CHTD7, FLT-4, FLT41, LMPH1A, LMPHM1, PCL}, NFKB1 (nuclear factor kappa B subunit 1) [NCBI Gene 4790] {aka CVID12, EBP-1, KBF1, NF-kB, NF-kB1, NF-kappa-B1}, IL13 (interleukin 13) [NCBI Gene 3596] {aka IL-13, P600}, CXCR1 (C-X-C motif chemokine receptor 1) [NCBI Gene 3577] {aka C-C, C-C-CKR-1, CD128, CD181, CDw128a, CKR-1}, CXCL8 (C-X-C motif chemokine ligand 8) [NCBI Gene 3576] {aka GCP-1, GCP1, IL8, LECT, LUCT, LYNAP}, IL5 (interleukin 5) [NCBI Gene 3567] {aka EDF, IL-5, TRF}, EGFR (epidermal growth factor receptor) [NCBI Gene 1956] {aka ERBB, ERBB1, ERRP, HER1, NISBD2, NNCIS}, VEGFD (vascular endothelial growth factor D) [NCBI Gene 2277] {aka FIGF, VEGF-D}, IL18 (interleukin 18) [NCBI Gene 3606] {aka IGIF, IL-18, IL-1g, IL1F4}, IL4 (interleukin 4) [NCBI Gene 3565] {aka BCGF-1, BCGF1, BSF-1, BSF1, IL-4}, VAMP8 (vesicle associated membrane protein 8) [NCBI Gene 8673] {aka EDB, VAMP-8}, TRBV20OR9-2 (T cell receptor beta variable 20/OR9-2 (non-functional)) [NCBI Gene 6962] {aka CDR3, TCRBV20S2, TCRBV2O, TCRBV2S2O}, CCL5 (C-C motif chemokine ligand 5) [NCBI Gene 6352] {aka D17S136E, RANTES, SCYA5, SIS-delta, SISd, TCP228}, IL1R1 (interleukin 1 receptor type 1) [NCBI Gene 3554] {aka CD121A, CRMO3, D2S1473, IL-1R-alpha, IL-1RT1, IL1R}, IL21 (interleukin 21) [NCBI Gene 59067] {aka CVID11, IL-21, Za11}, MLH1 (mutL homolog 1) [NCBI Gene 4292] {aka COCA2, FCC2, HNPCC, HNPCC2, LYNCH2, MLH-1}, MSH6 (mutS homolog 6) [NCBI Gene 2956] {aka GTBP, GTMBP, HNPCC5, HSAP, LYNCH5, MMRCS3}, VEGFA (vascular endothelial growth factor A) [NCBI Gene 7422] {aka L-VEGF, MVCD1, VEGF, VPF}, CXCL12 (C-X-C motif chemokine ligand 12) [NCBI Gene 6387] {aka IRH, PBSF, SCYB12, SDF1, TLSF, TPAR1}, IL6R (interleukin 6 receptor) [NCBI Gene 3570] {aka CD126, HIES5, IL-1Ra, IL-6R, IL-6R-1, IL-6RA}, MAPK14 (mitogen-activated protein kinase 14) [NCBI Gene 1432] {aka CSBP, CSBP1, CSBP2, CSPB1, EXIP, Mxi2}, MSH2 (mutS homolog 2) [NCBI Gene 4436] {aka COCA1, FCC1, HNPCC, HNPCC1, LCFS2, LYNCH1}, CXCL2 (C-X-C motif chemokine ligand 2) [NCBI Gene 2920] {aka CINC-2a, GRO2, GROb, MGSA-b, MIP-2a, MIP2}, IRAK2 (interleukin 1 receptor associated kinase 2) [NCBI Gene 3656] {aka IRAK-2}, IL33 (interleukin 33) [NCBI Gene 90865] {aka C9orf26, DVS27, IL1F11, NF-HEV, NFEHEV}, TP53 (tumor protein p53) [NCBI Gene 7157] {aka BCC7, BMFS5, LFS1, P53, TRP53}, CXCL6 (C-X-C motif chemokine ligand 6) [NCBI Gene 6372] {aka CKA-3, GCP-2, GCP2, SCYB6}, ALKBH5 (alkB homolog 5, RNA demethylase) [NCBI Gene 54890] {aka ABH5, OFOXD, OFOXD1}, CXCL9 (C-X-C motif chemokine ligand 9) [NCBI Gene 4283] {aka CMK, Humig, MIG, SCYB9, crg-10}, LTA (lymphotoxin alpha) [NCBI Gene 4049] {aka LT, TNFB, TNFSF1, TNLG1E}, PTEN (phosphatase and tensin homolog) [NCBI Gene 5728] {aka 10q23del, BZS, CWS1, DEC, GLM2, MHAM}, SMAD4 (SMAD family member 4) [NCBI Gene 4089] {aka DPC4, JIP, MADH4, MYHRS}, IFNG (interferon gamma) [NCBI Gene 3458] {aka IFG, IFI, IMD69}, APLN (apelin) [NCBI Gene 8862] {aka APEL, XNPEP2}, IL10RA (interleukin 10 receptor subunit alpha) [NCBI Gene 3587] {aka CD210, CD210a, CDW210A, HIL-10R, IL-10R1, IL10R}, BRAF (B-Raf proto-oncogene, serine/threonine kinase) [NCBI Gene 673] {aka B-RAF1, B-raf, BRAF-1, BRAF1, NS7, RAFB1}, CCL3 (C-C motif chemokine ligand 3) [NCBI Gene 6348] {aka G0S19-1, LD78, LD78ALPHA, MIP-1-alpha, MIP1A, SCI}, PPBP (pro-platelet basic protein) [NCBI Gene 5473] {aka B-TG1, Beta-TG, CTAP-III, CTAP3, CTAPIII, CXCL7}, ACKR3 (atypical chemokine receptor 3) [NCBI Gene 57007] {aka CMKOR1, CXC-R7, CXCR-7, CXCR7, GPR159, RDC-1}, ZEB1 (zinc finger E-box binding homeobox 1) [NCBI Gene 6935] {aka AREB6, BZP, DELTAEF1, FECD6, NIL2A, PPCD3} - **Diseases:** carcinogenesis (MESH:D063646), constipation (MESH:D003248), diarrhea (MESH:D003967), CAC (MESH:D000083023), colorectal adenomas (MESH:D000236), CMS (MESH:C535673), gastrointestinal cancer (MESH:D005770), fatigue (MESH:D005221), breast, prostate, pancreas, and colon cancers (MESH:D001943), obesity (MESH:D009765), depression (MESH:D003866), smoking (MESH:D015208), hypoxic (MESH:D002534), IBD (MESH:D015212), autoimmune diseases (MESH:D001327), nausea (MESH:D009325), hypoxia (MESH:D000860), Lynch syndrome (MESH:D003123), lupus (MESH:D008180), RCC (MESH:D002292), necrotic (MESH:D009336), fever (MESH:D005334), metabolic diseases (MESH:D008659), genetic abnormalities (MESH:D030342), multiple sclerosis (MESH:D009103), prostate, pancreatic, lung, gastric, and colon cancer (MESH:D010190), alcohol abuse (MESH:D000437), CRC (MESH:D015179), endometrium (MESH:D016889), hereditary (MESH:D009386), tumors of the kidney, lung, brain, prostate, colon, breast, pancreas, ovary, (MESH:D061325), precancerous lesions (MESH:D011230), tumorigenic (MESH:D002471), liver metastases (MESH:D009362), rheumatoid arthritis (MESH:D001172), melanoma (MESH:D008545), Inflammation (MESH:D007249), injury to (MESH:D014947), MDSCs (OMIM:601308), toxicity (MESH:D064420), abdominal pain (MESH:D015746), MSI-H (MESH:D053842), Adenomatous Polyposis Coli (MESH:D011125), chills (MESH:D023341), colitis (MESH:D003092), CMS3 cancers (MESH:D009369), benign gastrointestinal dysfunction (MESH:D005767), infection (MESH:D007239), blood coagulation (MESH:D001778) - **Chemicals:** PGE2 (MESH:D015232), panitumumab (MESH:D000077544), lipid (MESH:D008055), peptides (MESH:D010455), LPS (MESH:D008070), leucovorin (MESH:D002955), NOX-A12 (MESH:C587878), 5-fluorouracil (MESH:D005472), polyamines (MESH:D011073), ROS (MESH:D017382), AMD3100 (MESH:C088327), flavonoid (MESH:D005419), Bevacizumab (MESH:D000068258), ATI-2341 (MESH:C586629), ipilimumab (MESH:D000074324), maraviroc (MESH:D000077592), nivolumab (MESH:D000077594), CTCE-9908 (MESH:C540323), bicyclam (MESH:D000080027), oxygen (MESH:D010100), dostarlimab (MESH:C000719628), ornithine (MESH:D009952), CVX15 (-), LY2510924 (MESH:C000595455), ramucirumab (MESH:C543333), fatty acids (MESH:D005227), carbohydrates (MESH:D002241), cetuximab (MESH:D000068818), amino acids (MESH:D000596), Pembrolizumab (MESH:C582435), BMS-936564 (MESH:C581980) - **Species:** Homo sapiens (human, species) [taxon 9606], Mus musculus (house mouse, species) [taxon 10090] - **Mutations:** V600E, rs2070874, H17 T - **Cell lines:** HCT 116 — Homo sapiens (Human), Colon carcinoma, Cancer cell line (CVCL_0291), RKO — Homo sapiens (Human), Colon carcinoma, Cancer cell line (CVCL_0504), Caco-2 — Homo sapiens (Human), Colon adenocarcinoma, Cancer cell line (CVCL_0025) ## Full text _Full body text omitted from this summary view._ Fetch the complete paper as Markdown: https://tomesphere.com/paper/PMC12941250/full.md ## Figures 4 figures with captions in the complete paper: https://tomesphere.com/paper/PMC12941250/full.md ## References 108 references — full list in the complete paper: https://tomesphere.com/paper/PMC12941250/full.md --- Source: https://tomesphere.com/paper/PMC12941250