Chemotherapy Strategies for Advanced Colorectal Cancer Management

Advanced colorectal cancer presents significant clinical challenges owing to its propensity for metastatic dissemination and the development of chemoresistance. Contemporary management strategies combine fluoropyrimidine-based cytotoxics, notably 5-fluorouracil (5-FU) or its oral prodrug capecitabine, with platinum compounds such as oxaliplatin or topoisomerase inhibitors like irinotecan. These backbone regimens have been enhanced through incorporation of targeted agents and novel administration schedules. Antiangiogenic therapies, for example bevacizumab, and small-molecule tyrosine kinase inhibitors have been introduced to disrupt tumour vascular supply. Maintenance therapy following induction aims to prolong disease control while mitigating cumulative toxicity. Efforts to overcome resistance include the exploitation of drug synergism, repurposing of proteasome inhibitors and optimisation of prodrug activation pathways. Across all approaches, individualised selection guided by patient performance status, comorbidities and molecular biomarkers underpins decision-making. Emerging research explores both systemic combinations and innovative delivery systems designed to improve tumour selectivity and reduce off-target effects.

Research from Nature Portfolio

Recent laboratory investigations have demonstrated that combining the folate modulator leucovorin with the proteasome inhibitor bortezomib yields a synergistic induction of apoptosis in colorectal cancer cell lines and xenograft models. This novel pairing enhances caspase activation and leads to greater tumour growth inhibition than either agent alone. By repurposing an approved proteasome inhibitor, researchers aim to exploit leucovorin’s favourable safety profile to counteract resistance to standard 5-FU-based chemotherapy.

Chemotherapy Strategies for Advanced Colorectal Cancer Management publication trend

The graph below shows the total number of articles in chemotherapy strategies for advanced colorectal cancer management across all publications each year (not limited to Nature Index journals).

Technical terms

Prodrug: A compound administered in an inactive or less active form that is converted in the body into an active pharmacological agent.

Tyrosine kinase inhibitor: A small molecule that blocks the enzymatic activity of tyrosine kinases involved in signalling pathways that drive tumour growth and angiogenesis.

Proteasome inhibitor: A drug that impedes proteasome-mediated protein degradation, leading to accumulation of pro-apoptotic factors and cancer cell death.

Objective response rate (ORR): The proportion of patients whose tumours shrink or disappear following treatment, according to predefined criteria.

Progression-free survival (PFS): The duration of time during and after treatment in which a patient’s disease does not worsen.

References

1. Anlotinib plus chemotherapy as a first-line treatment for gastrointestinal cancer patients with unresectable liver metastases: a multicohort, multicenter, exploratory trial. Signal Transduction and Targeted Therapy (2024).
2. In vitro co-culture systems of hepatic and intestinal cells for cellular pharmacokinetic and pharmacodynamic studies of capecitabine against colorectal cancer. Cancer Cell International (2023).
3. Comparison of irinotecan and oxaliplatin as the first-line therapies for metastatic colorectal cancer: a meta-analysis. BMC Cancer (2021).
4. Leucovorin Enhances the Anti-cancer Effect of Bortezomib in Colorectal Cancer Cells. Scientific Reports (2017).