Blood Test Predicts Chemotherapy Benefit; CLK3 Drives Colorectal Cancer Angiogenesis

A blood test may help identify which patients with colorectal cancer that has spread to the liver are most likely to benefit from chemotherapy after surgery, according to research presented at the ESMO Gastrointestinal Cancers Congress 2026. The Phase II GALAXY study, led by researchers from Hyogo Medical University, Japan, together with collaborators including the University of Oxford, UK, found that among patients who underwent upfront surgery and had detectable circulating tumour DNA (ctDNA) after surgery, those who received adjuvant chemotherapy had markedly better outcomes than those who did not. At four years after surgery, overall survival was 65% compared with 33%, while disease-free survival was 38% compared with 7%.

The study included 298 patients who underwent surgery for colorectal liver metastases and had ctDNA measured between two and 10 weeks after surgery using a personalized, tumor-informed blood test. Of these, 191 underwent upfront surgery, while 107 received neoadjuvant chemotherapy before surgery. Detectable ctDNA was strongly associated with poorer outcomes: patients with a positive ctDNA test had more than four times the risk of cancer recurrence and more than nine times the risk of death compared with those whose ctDNA test was negative. Among patients with detectable ctDNA who underwent upfront surgery, adjuvant chemotherapy was associated with a 93% reduction in the risk of recurrence. By contrast, patients without detectable ctDNA had favourable long-term outcomes regardless of whether they received adjuvant chemotherapy. Among patients who had already received chemotherapy before surgery, ctDNA remained a strong predictor of recurrence and survival, but additional chemotherapy after surgery was not associated with improved outcomes regardless of ctDNA status. Colorectal cancer is the third most common cancer worldwide and the second leading cause of cancer death, and the liver is the most common site of metastatic spread.

In a separate study, researchers investigated the role of CDC-like kinase 3 (CLK3) in tumor angiogenesis in colorectal cancer. Bioinformatic analysis of clinical datasets revealed that CLK3 expression positively correlated with angiogenesis-related pathways in colorectal cancer. In vitro and in vivo experiments confirmed that CLK3 overexpression promoted tumor angiogenesis, whereas CLK3 knockout inhibited this process. Mechanistically, CLK3 directly interacted with and stabilized hypoxia-inducible factor 1-alpha (HIF1α) by inhibiting its ubiquitin-proteasome-mediated degradation, and promoted the phosphorylation of HIF1α at tyrosine residues. Functional assays confirmed that CLK3-mediated tumor angiogenesis was dependent on HIF1α. These findings highlight the importance of CLK3 in regulating tumor angiogenesis and provide evidence for targeting CLK3 as a potential therapeutic strategy for colorectal cancer treatment.