Systemic treatment for metastatic colorectal cancer

Abstract

Significant progress has been achieved in the treatment of metastatic colorectal cancer (mCRC) patients during the last 20 years. There are currently numerous treatments available for the first-line treatment of mCRC. Sophisticated molecular technologies have been developed to reveal novel prognostic and predictive biomarkers for CRC. The development of next-generation sequencing and whole-exome sequencing, which are strong new tools for the discovery of predictive molecular biomarkers to facilitate the delivery of customized treatment, has resulted in tremendous breakthroughs in DNA sequencing technology in recent years. The appropriate adjuvant treatments for mCRC patients are determined by the tumor stage, presence of high-risk pathologic characteristics, microsatellite instability status, patient age, and performance status. Chemotherapy, targeted therapy, and immunotherapy are the main systemic treatments for patients with mCRC. Despite the fact that these novel treatment choices have increased overall survival for mCRC, survival remains optimal for individuals with non-metastatic disease. The molecular technologies currently being used to support our ability to practice personalized medicine; the practical aspects of applying molecular biomarkers to regular clinical practice; and the evolution of chemotherapy, targeted therapy, and immunotherapy strategies for the treatment of mCRC in the front-line setting are all reviewed here.

Keywords: Biomarkers; Chemotherapy; Immunotherapy; Metastatic colorectal cancer; Personalized medicine; Systemic treatment; Targeted therapy.

Figure 1

Three molecular pathways can lead to colorectal cancer. For colorectal carcinogenesis, three molecular pathways have been proposed: the chromosomal instable or classic pathway, the microsatellite instability pathway, and the serrated pathway. APC: Adenomatous polyposis coli; BRAF: Protein kinase B-Raf; CIMP: CpG island methylator phenotype; KRAS: Kristin rat sarcoma virus.

Figure 2

Targeted therapy for metastatic colorectal cancer. AKT: Ak strain transforming; D: Down regulation pathway; EGFR: Epidermal growth factor receptor; HER2: Human epidermal growth factor receptor 2; IRS1/2: Insulin receptor substrates 1 or 2; MAPK: Mitogen activated protein kinase; mTOR: Mammalian target of rapamycin; MEK: Mitogen-activated protein kinase kinase; NTRK: Neurotrophic tyrosine receptor kinase; PTEN: Phosphatase and tensin homolog; PI3K: Phosphoinositide 3-kinases; RAF: Rapidly accelerated fibrosarcoma; RAS: Rat sarcoma virus; SOS: Son of sevenless.

Figure 3

Immune check point inhibitors treatment for metastatic colorectal cancer. CTLA4: Cytotoxic T-lymphocyte-associated protein 4; MHC: Major histocompatibility complex; PD-1: Programmed cell death protein 1; PD-L1: Programmed death-ligand; TCR: T cell receptor.