Advancements in Targeted Therapies for Colorectal Cancer: Overcoming Challenges and Exploring Future Directions

Area of Science:

• Oncology
• Molecular Biology
• Cancer Therapeutics

Background:

• Colorectal cancer (CRC) is a major global health challenge, with advanced stages often diagnosed late.
• Effective and less toxic therapeutic targets are crucial for improving outcomes in advanced CRC.

Purpose of the Study:

• To review recent advancements in targeted therapies for colorectal cancer, focusing on HER inhibitors.
• To assess the efficacy of monoclonal antibodies (mAbs) and tyrosine kinase inhibitors (TKIs) and explore resistance mechanisms.
• To discuss future directions, including novel biomarkers and combination therapies.

Main Methods:

• Review of current literature on targeted therapies for colorectal cancer.
• Assessment of efficacy and resistance mechanisms of HER inhibitors (mAbs, TKIs).
• Exploration of emerging therapeutic strategies like dual TKIs, ADCs, bispecific antibodies, and CAR-T cells.

Main Results:

• Targeted therapies like cetuximab and panitumumab have shown efficacy in KRAS wild-type CRC.
• Resistance mechanisms and tumor heterogeneity present significant challenges.
• Novel approaches such as dual TKIs, ADCs, bispecific antibodies, and CAR-T cells show promise.

Conclusions:

• Targeted therapies have transformed CRC treatment, but challenges remain.
• Further research is needed to address late diagnosis, tumor heterogeneity, and biomarker discovery.
• Future directions include developing next-generation inhibitors, drug repurposing, and immunotherapy combinations.