From Molecular Biology to Clinical Trials: Toward Personalized Colorectal Cancer Therapy

Area of Science:

• Oncology
• Genomics
• Molecular Biology

Background:

• High-throughput molecular studies have identified critical genetic and epigenetic alterations in colorectal cancer (CRC), including mutations, DNA methylations, and chromosomal changes.
• These alterations dysregulate key cellular signaling pathways controlling metabolism, proliferation, differentiation, and survival, impacting treatment efficacy.
• While targeted therapies have improved CRC treatment, a significant portion of patients, especially those with metastatic CRC, show resistance and limited benefit.

Purpose of the Study:

• To provide an updated review of the main molecular features of colorectal cancer (CRC).
• To summarize current targeted therapies for CRC being investigated in clinical trials.
• To classify CRC clinical trials to offer an overview of preclinical study perspectives.

Main Methods:

• Review of current literature on molecular alterations in colorectal cancer.
• Analysis of targeted therapies and their mechanisms of action in CRC.
• Unsupervised classification of ongoing CRC clinical trials.

Main Results:

• Genomic and epigenomic alterations are confirmed drivers of CRC progression and therapeutic resistance.
• Targeted therapies show promise but are limited by resistance mechanisms.
• An unsupervised classification of clinical trials provides insights into future research directions.

Conclusions:

• A deeper understanding of CRC's molecular landscape is essential for overcoming therapeutic resistance.
• Integrating basic research with preclinical studies is vital for developing novel, effective CRC treatments.
• The classification of clinical trials highlights the evolving landscape of CRC therapeutic development.