Biologics in rectal cancer

Area of Science:

• Oncology
• Gastroenterology
• Pharmacology

Background:

• Locally advanced rectal cancer (LARC) has high recurrence rates despite multimodality therapy.
• Fluoropyrimidine-based chemotherapy and radiation therapy (RT) are standard neoadjuvant treatments for LARC.
• Novel therapeutic strategies are needed to improve clinical outcomes for rectal cancer patients.

Purpose of the Study:

• To review completed and ongoing clinical trials on biological therapies for rectal cancer.
• To summarize the role of monoclonal antibodies, immune checkpoint inhibitors (ICIs), antibody-drug conjugates, bispecific antibodies, and gene therapies.
• To discuss the potential of personalized management in rectal cancer based on molecular biology.

Main Methods:

• Literature review of clinical trials in rectal cancer.
• Analysis of data on biological therapies including targeted therapy, antiangiogenics, and immunotherapy.
• Evaluation of findings in both metastatic and neoadjuvant settings for colorectal cancer (CRC).

Main Results:

• Microsatellite instability (MSI) tumors show high sensitivity to immune checkpoint inhibitors (ICIs).
• Preliminary findings for ICIs in the neoadjuvant rectal cancer setting are promising.
• Antiangiogenic and anti-EGFR therapies have not shown significant benefit in LARC compared to metastatic disease.

Conclusions:

• Advances in molecular biology of CRC offer optimism for personalized rectal cancer management.
• Biomarker-guided therapy in metastatic CRC will inform future biological therapy development in LARC.
• Further research into novel biological therapies is crucial for improving rectal cancer treatment outcomes.