The thioredoxin system is essential for many physiological processes, including the maintenance of redox signalling pathways. Alterations in the activity, expression and interactions with other signalling pathways can lead to protective or pathophysiological responses. Thioredoxin and thioredoxin reductase, the two main components of this system, are often overexpressed in cancer, including colorectal cancer. This overexpression is often linked with tumour progression and poor outcomes. This review discusses the role of the Trx system in driving colorectal carcinogenesis and disease progression, as well as the challenges of targeting this system. Additionally, the recent advancements in the development of novel and effective thioredoxin inhibitors for colorectal cancer are also explored.

IEDB screen for MHC class II binding epitopes

Overview of EC50 values for in vitro cytotoxicity of CH129-ADC compounds

Comparison of FG129 and CA19.9 mAb SPM110 binding (both at 7.4 nmol/L) to a panel of normal human tissues (AMSBIO TMA)

Supplementary Figure 3. containing direct cytotoxic activity of FG88.2: PI uptake and WST-8 assay. DNA fragmentation analysis of FG88-treated cells.

Overview of the kinetic binding parameters of the parental 88 mAbs

Supplementary Table 2. containing IHC scoring of FG88.2 and FG88.7 binding to AMS bio normal human tissue

FG129 binding to cancer cell lines, but not PBMC or HUVEC

Supplementary Table 1. containing kinetic and equilibrium binding parameters for FG88.2 and FG88.7

Limited normal human tissue distribution of FG129 glyco-epitope

Supplementary Materials and Methods relating to Flow Cytometry, Lewis ELISA, Affinity Analysis and DNA Fragmentation

Individual tumor growth curves from mice included in the in vivo COLO205 xenograft model

Supplementary Table 3. containing FG88 glyco-epitope expression on human tumor types. Overview of tumor TMA scoring.

Supplementary Figure 2. containing FG88.2 binding to normal CN monkey TMA and evaluation of FG88.2 binding to PBMCs, granulocytes and erythrocytes. Sandwich ELISA for saliva Lewis a detection.

Negligible direct cell killing ability by i129G1 on low to moderate binding cancer cell lines compared to the high-binding COLO205

In vitro non-target mediated CH129-ADC cytotoxicity on the antigen-negative AGS cells

Effective cellular internalization and immune effector functions by FG129

FG129 and CH129 target their glyco-epitope in vitro with nanomolar functional affinity

Targeted molecular imaging may improve tumor cell identification during diagnosis and resection of pancreatic ductal adenocarcinoma (PDAC). Although many molecular imaging biomarkers are (over)expressed in PDAC, intertumoral heterogeneity of biomarker expression hampers universal tracer administration. Preoperative, patient-specific screening and selection of the most optimal biomarker could therefore improve tumor delineation. This study evaluated whether fine-needle biopsy (FNB) specimens could be used to preoperatively predict biomarker expression in the corresponding primary PDAC specimen. Expression of previously identified PDAC biomarkers αvβ6, CEACAM5, EGFR, mesothelin, Lea/c/x, and sdi-Lea on FNB and corresponding primary tumor (PT) specimens (n = 45) was evaluated using immunohistochemistry and quantified using a semi-automated image analysis workflow. Biomarker expression on FNB and PT tissues showed high concordance (∆H-score ≤ 50), i.e. was present in 62

Supplementary Figure 1. containing Lewis glycan competition analysis, Lewis a ELISA (titration for EC50) and HCT-15 cell surface binding (titration for Kd)