From bench to bedside: the development journey of fruquintinib as a colorectal cancer therapy.

Introduction: Fruquintinib is a novel oral tyrosine kinase inhibitor (TKI) with high selectivity for vascular endothelial growth factor receptors (VEGFR), which play a key role in tumor angiogenesis. Blocking this pathway represents an essential strategy in the continuum of care of patients with metastatic colorectal cancer (mCRC). Fruquintinib has been recently approved as monotherapy for refractory mCRC based on the FRESCO and FRESCO-2 pivotal trials, which demonstrated significant overall survival (OS) benefits compared to placebo, with manageable toxicity.

Areas covered: This article summarizes the preclinical development, pharmacology, clinical safety, and efficacy of fruquintinib in refractory mCRC patients and discusses current and future research to optimize its use as monotherapy and in combination with other treatments and potentially expand its use to earlier treatment lines and other types of cancer. A literature search (Dec 2024) was conducted in MEDLINE and EMBASE, and abstracts from major oncology conferences (AACR, ASCO, and ESMO) were reviewed.

Expert opinion: Fruquintinib expands the treatment armamentarium for patients with refractory mCRC, providing additional survival. Its high selectivity for VEGFR may minimize off-target effects, improving patients' safety and tolerability. Further research on combination strategies and biomarkers will be key to optimizing patient selection and broadening their clinical applications.