Molecular targeted therapy for metastatic colorectal cancer: current and evolving approaches

Furong Li; Yanping Lin; Rong Li; Xin Shen; Mengying Xiang; Guangrui Xiong; Ke Zhang; Tingrong Xia; Jiangyan Guo; Zhonghui Miao; Yedan Liao; Xuan Zhang; Lin Xie

doi:10.3389/fphar.2023.1165666

Molecular targeted therapy for metastatic colorectal cancer: current and evolving approaches

Front Pharmacol. 2023 Oct 20:14:1165666. doi: 10.3389/fphar.2023.1165666. eCollection 2023.

Authors

Furong Li^#¹, Yanping Lin^#², Rong Li^#², Xin Shen², Mengying Xiang², Guangrui Xiong², Ke Zhang², Tingrong Xia², Jiangyan Guo³, Zhonghui Miao², Yedan Liao², Xuan Zhang¹, Lin Xie²

Affiliations

¹ Department of Colorectal Surgery, The Third Affiliated Hospital of Kunming Medical University, Yunnan Cancer Hospital, Kunming, China.
² Department of Gastroenterology and Internal Oncology, The Third Affiliated Hospital of Kunming Medical University, Yunnan Cancer Hospital, Kunming, China.
³ Department of Pathology, The Third Affiliated Hospital of Kunming Medical University, Yunnan Cancer Hospital, Kunming, China.

^# Contributed equally.

Abstract

Colorectal cancer (CRC) represents 10% of all cancer types, making it the third leading cause of cancer-related deaths globally. Metastasis is the primary factor causing mortality in CRC patients. Approximately 22% of CRC-related deaths have metastasis present at diagnosis, with approximately 70% of these cases recurring. Recently, with the application of novel targeted drugs, targeted therapy has become the first-line option for individualized and comprehensive treatment of CRC. The management of these patients remains a significant medical challenge. The most prevalent targeted therapies for CRC in clinical practice focus on anti-vascular endothelial growth factor and its receptor, epidermal growth factor receptor (EGFR), and multi-target kinase inhibitors. In the wake of advancements in precision diagnosis and widespread adoption of second-generation sequencing (NGS) technology, rare targets such as BRAF V600E mutation, KRAS mutation, HER2 overexpression/amplification, and MSI-H/dMMR in metastatic colorectal cancer (mCRC) are increasingly being discovered. Simultaneously, new therapeutic drugs targeting these mutations are being actively investigated. This article reviews the progress in clinical research for developing targeted therapeutics for CRC, in light of advances in precision medicine and discovery of new molecular target drugs.

Keywords: Her-2; RAS; VEGF; colorectal cancer; epidermal growth factor receptor; molecular targeted therapy.

Publication types

Review

Grants and funding

This research was funded by the Key Project of Applied Basic Research in Yunnan Province (No. 202101AS070004) and the Joint Special Project of Applied Basic Research of Yunnan Provincial Science and Technology Department and Kunming Medical University (No. 202001AY070001-073).