# Electrochemical Biosensors for Cancer Diagnosis and Prognosis Using Protein Biomarkers: Current Trends, Advances, and Clinical Translation Potential

**Authors:** Michael E. J. López Mujica, Elena E. Ferapontova

PMC · DOI: 10.3390/s26041139 · Sensors (Basel, Switzerland) · 2026-02-10

## TL;DR

This paper reviews electrochemical biosensors for detecting cancer-related proteins in blood, aiming to improve early diagnosis and treatment.

## Contribution

The paper provides a critical review of recent advances in electrochemical biosensors for cancer protein biomarkers and discusses barriers to clinical translation.

## Key findings

- Many electrochemical biosensor approaches have achieved high analytical sensitivity for serum protein detection.
- Key barriers to clinical translation include complex sample matrix effects and limited validation with patient samples.
- The paper emphasizes the need for rigorous standardization and validation of biosensors for clinical use.

## Abstract

Cancer, a disease with high mortality, represents a major public health challenge. Increased access to early tumor screening, especially non-invasive liquid biopsy assays targeting blood-circulating protein biomarkers, has advanced cancer diagnosis and treatment, but these assays are still scarce. This work critically reviews general strategies for the rapid and accurate electrochemical detection of serum proteins and surveys recent advances in liquid biopsy electrochemical biosensors targeting cancer-related proteins. Many of these approaches have achieved remarkable analytical sensitivity. The review further addresses key barriers to clinical translation and commercialization, including complex sample matrix effects that require rigorous standardization of preanalytical and analytical workflows, limited validation using patient samples, difficulties in accounting for interpatient variability, and practical considerations such as manufacturability, cost-effective scale-up, and long-term stability. Accordingly, particular emphasis is placed on clinically translatable detection methods, with a focus on the analytical and clinical validation of biosensors.

## Linked entities

- **Diseases:** cancer (MONDO:0004992)

## Full-text entities

- **Genes:** IGF1 (insulin like growth factor 1) [NCBI Gene 3479] {aka IGF, IGF-I, IGFI, MGF}, CD79A (CD79a molecule) [NCBI Gene 973] {aka IGA, IGAlpha, MB-1, MB1}, SPP1 (secreted phosphoprotein 1) [NCBI Gene 6696] {aka BNSP, BSPI, ETA-1, OPN}, CD81 (CD81 molecule) [NCBI Gene 975] {aka CVID6, S5.7, TAPA1, TSPAN28}, ALB (albumin) [NCBI Gene 213] {aka FDAHT, HSA, PRO0883, PRO0903, PRO1341}, TGFB1 (transforming growth factor beta 1) [NCBI Gene 7040] {aka CAEND1, CED, DPD1, IBDIMDE, LAP, TGF-beta1}, LCN2 (lipocalin 2) [NCBI Gene 3934] {aka 24p3, MSFI, NGAL, p25}, AFP (alpha fetoprotein) [NCBI Gene 174] {aka AFPD, FETA, HPAFP}, ATHS (atherosclerosis susceptibility (lipoprotein associated)) [NCBI Gene 470] {aka ALP}, MUC16 (mucin 16, cell surface associated) [NCBI Gene 94025] {aka CA125}, FLT1 (fms related receptor tyrosine kinase 1) [NCBI Gene 2321] {aka FLT, FLT-1, VEGFR-1, VEGFR1}, HAS1 (hyaluronan synthase 1) [NCBI Gene 3036] {aka HAS}, CD63 (CD63 molecule) [NCBI Gene 967] {aka AD1, HOP-26, ME491, MLA1, OMA81H, Pltgp40}, MFSD11 (major facilitator superfamily domain containing 11) [NCBI Gene 79157] {aka ET}, KDR (kinase insert domain receptor) [NCBI Gene 3791] {aka CD309, FLK1, VEGFR, VEGFR2}, CRP (C-reactive protein) [NCBI Gene 1401] {aka PTX1}, IL6 (interleukin 6) [NCBI Gene 3569] {aka BSF-2, BSF2, CDF, HGF, HSF, IFN-beta-2}, AKT1 (AKT serine/threonine kinase 1) [NCBI Gene 207] {aka AKT, PKB, PKB-ALPHA, PRKBA, RAC, RAC-ALPHA}, CD44 (CD44 molecule (IN blood group)) [NCBI Gene 960] {aka CDW44, CSPG8, ECM-III, ECMR-III, H-CAM, HCELL}, CEACAM3 (CEA cell adhesion molecule 3) [NCBI Gene 1084] {aka CD66D, CEA, CGM1, CGM1a, W264, W282}, GOLM1 (golgi membrane protein 1) [NCBI Gene 51280] {aka C9orf155, GOLPH2, GP73, HEL46, PSEC0257, bA379P1.3}, VEGFA (vascular endothelial growth factor A) [NCBI Gene 7422] {aka L-VEGF, MVCD1, VEGF, VPF}, HAO1 (hydroxyacid oxidase 1) [NCBI Gene 54363] {aka GO, GOX, GOX1, HAOX1}, EGF (epidermal growth factor) [NCBI Gene 1950] {aka HOMG4, URG}, mucin [NCBI Gene 100508689], CYGB (cytoglobin) [NCBI Gene 114757] {aka HGB, NOD, STAP}, IFNG (interferon gamma) [NCBI Gene 3458] {aka IFG, IFI, IMD69}, MB (myoglobin) [NCBI Gene 4151] {aka MYOSB, PVALB}, TNNI3 (troponin I3, cardiac type) [NCBI Gene 7137] {aka CMD1FF, CMD2A, CMH7, RCM1, TNNC1, cTnI}, TGFA (transforming growth factor alpha) [NCBI Gene 7039] {aka TFGA}, F2 (coagulation factor II, thrombin) [NCBI Gene 2147] {aka PT, RPRGL2, THPH1}, IL2 (interleukin 2) [NCBI Gene 3558] {aka IL-2, TCGF, lymphokine}, MIR21 (microRNA 21) [NCBI Gene 406991] {aka MIRN21, hsa-mir-21, miR-21, miRNA21}, BMP1 (bone morphogenetic protein 1) [NCBI Gene 649] {aka OI13, PCOLC, PCP, TLD}, PLAU (plasminogen activator, urokinase) [NCBI Gene 5328] {aka ATF, BDPLT5, QPD, UPA, URK, u-PA}, KLK3 (kallikrein related peptidase 3) [NCBI Gene 354] {aka APS, KLK2A1, PSA, hK3}, TXK (TXK tyrosine kinase) [NCBI Gene 7294] {aka BTKL, PSCTK5, PTK4, RLK, TKL}, EGFR (epidermal growth factor receptor) [NCBI Gene 1956] {aka ERBB, ERBB1, ERRP, HER1, NISBD2, NNCIS}, CXCL8 (C-X-C motif chemokine ligand 8) [NCBI Gene 3576] {aka GCP-1, GCP1, IL8, LECT, LUCT, LYNAP}, ERBB2 (erb-b2 receptor tyrosine kinase 2) [NCBI Gene 2064] {aka CD340, HER-2, HER-2/neu, HER2, MLN 19, MLN-19}, HLA-G (major histocompatibility complex, class I, G) [NCBI Gene 3135] {aka MHC-G}, PIK3CB (phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit beta) [NCBI Gene 5291] {aka P110BETA, PI3K, PI3KBETA, PIK3C1}, IDH1 (isocitrate dehydrogenase (NADP(+)) 1) [NCBI Gene 3417] {aka HEL-216, HEL-S-26, IDCD, IDH, IDP, IDPC}, MUC1 (mucin 1, cell surface associated) [NCBI Gene 4582] {aka ADMCKD, ADMCKD1, ADTKD2, CA 15-3, CD227, Ca15-3}, GAPDH (glyceraldehyde-3-phosphate dehydrogenase) [NCBI Gene 2597] {aka G3PD, GAPD, HEL-S-162eP}
- **Diseases:** non-seminomatous germ cell tumors (MESH:C537844), metastatic diseases (MESH:D000092182), epithelial malignancies (MESH:D002277), benign prostatic hyperplasia (MESH:D011470), lung cancer (MESH:D008175), infection (MESH:D007239), ET (MESH:D054069), cancers (MESH:D009369), uterine cancer (MESH:D014594), NH (MESH:C536394), COVID-19 (MESH:D000086382), breast, bladder and ovarian cancers (MESH:D061325), NM (MESH:C536816), pancreatic cancer (MESH:D010190), viral hepatitis (MESH:D014777), colorectal and other cancers (MESH:D015179), inflammation (MESH:D007249), pancreatic, gastric, lung, breast and other gastrointestinal cancers (MESH:C537262), chronic liver diseases (MESH:D008107), osteosarcoma (MESH:D012516), benign disease (MESH:D004194), injury to (MESH:D014947), metastases (MESH:D009362), mutant (MESH:D016115), non-melanoma (MESH:D008545), cirrhosis (MESH:D005355), gliomas (MESH:D005910), PCa (MESH:D011471), non-small cell lung cancer (MESH:D002289), glioblastoma (MESH:D005909), head and neck squamous cell carcinoma (MESH:D000077195), infectious diseases (MESH:D003141), breast, lung, colorectal, gastric, pancreatic, hepatocellular, prostate, and ovarian cancers (MESH:D011472), hypoxia (MESH:D000860), HCC (MESH:D006528), esophageal cancer (MESH:D004938), hematological tumors (MESH:D019337), mixed germ cell tumors (MESH:D009373), yolk sac tumors (MESH:D018240), gastric, pancreatic, and other gastrointestinal cancers (MESH:D005770), hepatocellular injury (MESH:D056486), breast, ovarian, pancreatic, and lung cancer (MESH:D010051), non-Hodgkin (MESH:D008228), obesity (MESH:D009765), breast and esophageal cancers (MESH:D001943), autoimmune conditions (MESH:D001327)
- **Chemicals:** amine (MESH:D000588), hydrazine (MESH:C029424), 1,2-diaminobenzene (MESH:C034193), polycaprolactone (MESH:C016240), CS-FC (MESH:D017402), TCA (MESH:D014238), polymer (MESH:D011108), Arg (MESH:D001120), guanine (MESH:D006147), epoxy (MESH:D004853), Carbon (MESH:D002244), PC (MESH:C053518), 3,3',5,5'-tetramethylbenzidine (MESH:C021758), Graphene oxide (MESH:C000628730), AC (MESH:D000186), MX (MESH:C054121), Fc (MESH:C004998), 1-naphthol (MESH:C029350), NiS (MESH:D009532), PPy (MESH:C067635), COF (MESH:D000073396), MIP (MESH:D000082582), C-N (MESH:D002395), lactate (MESH:D019344), Glycan (MESH:D011134), nitrogen (MESH:D009584), chromium (MESH:D002857), DA (MESH:C025953), CdTe (MESH:C028337), AA (MESH:D000596), BiVO4 (MESH:C091754), PEI (MESH:D011094), choline (MESH:D002794), His (MESH:D006639), Nafion (MESH:C040402), PEG (MESH:D011092), Uric acid (MESH:D014527), carbon nanotube (MESH:D037742), ferrocene (Fc) carboxylic acid (MESH:C032949), urea (MESH:D014508), poly(styrene sulfonate) (MESH:C003321), PBA (MESH:C010686), chitosan (MESH:D048271), Prussian-blue (MESH:C000170), SiO2 (MESH:D012822), ferrocyanide (MESH:C020354), SA (MESH:D000464), MCH (MESH:D016210), sulfide (MESH:D013440), CTP (MESH:D003570), glycerol (MESH:D005990), Ru (MESH:D012428), K3Fe(CN)6 (MESH:C028033), N-Ethyl-N'-(3-dimethylaminopropyl)-carbodiimide (MESH:C569266), g-C3N4 (MESH:C000629596), ferricyanide (MESH:C007931), GTP (MESH:D006160), Platinum (MESH:D010984), 2,3-diaminophenazine (MESH:C054312), Graphene (MESH:D006108)
- **Species:** Homo sapiens (human, species) [taxon 9606], Bos taurus (bovine, species) [taxon 9913]
- **Mutations:** A750del
- **Cell lines:** NU66-d@NR — Homo sapiens (Human), Oral cavity squamous cell carcinoma, Cancer cell line (CVCL_WI75)

## Full text

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## Figures

4 figures with captions in the complete paper: https://tomesphere.com/paper/PMC12944742/full.md

## References

199 references — full list in the complete paper: https://tomesphere.com/paper/PMC12944742/full.md

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Source: https://tomesphere.com/paper/PMC12944742