Emerging Frontiers in Colorectal Cancer Therapy: From Targeted Molecules to Immunomodulatory Breakthroughs and Cell-Based Approaches

Abstract

Colorectal cancer (CRC) is ranked as the second leading cause of cancer-related deaths globally, necessitating urgent advancements in therapeutic approaches. The emergence of groundbreaking therapies, including chimeric antigen receptor-T (CAR-T) cell therapies, oncolytic viruses, and immune checkpoint inhibitors, marks a transformative era in oncology. These innovative modalities, tailored to individual genetic and molecular profiles, hold the promise of significantly enhancing patient outcomes. This comprehensive review explores the latest clinical trials and advancements, encompassing targeted molecular therapies, immunomodulatory agents, and cell-based therapies. By evaluating the strengths, limitations, and potential synergies of these approaches, this research aims to reshape the treatment landscape and improve clinical outcomes for CRC patients, offering new found hope for those who have exhausted conventional options. The culmination of this work is anticipated to pave the way for transformative clinical trials, ushering in a new era of personalized and effective CRC therapy.

Keywords: CAR-T-cell therapies; Colorectal cancer; Immune checkpoint inhibitors; Oncolytic viruses; Targeted molecular therapies.

Fig. 1

Visualizing the Tumorigenesis Cascade. Beginning with normal epithelium, the Wnt/APC signaling pathway is disrupted, leading to the formation of polyps due to the loss of tumor suppressor genes. Subsequently, activation of the oncogene KRAS in the RAS/BRAF pathway transforms these small polyps into large benign adenomas. As the journey continues, defects in the P53 gene, coupled with additional mutations and escalating microsatellite instability and chromosomal instability, culminate in the transition from large benign polyps to malignant tumors, providing a vivid portrayal of the intricate molecular evolution underlying tumorigenesis

Fig. 2

Novel therapies for CRC. This diagram shows the various types of cancer vaccines and targeted therapies that are being investigated for the treatment of CRC. The vaccines target different molecular targets and signaling pathways, including RAS, RAF, HER2, PIK3CA, BRAF, NTRK, and mismatch repair. The targeted therapies include monoclonal antibodies (MABs), cytokines, and viral vector vaccines

Fig. 3

Timeline of FDA-approved targeted therapy for colorectal cancer. VEGF vascular endothelial growth factor, EGFR epidermal growth factor receptor, NTRK neurotrophic tropomyosin receptor kinase, IDH1 isocitrate dehydrogenase 1

Fig. 4

Unlocking Immune Potential: in the first frame, PD1 engages with PDL1, stifling T-cell activation through immune checkpoint inhibition. The second frame depicts the pivotal role of immune checkpoint inhibitors, releasing this suppressive interaction and reinvigorating T-cell activation, showcasing the promise of immunotherapy in unleashing the body’s innate defenses against cancer