EGFR-Based Targeted Therapy for Colorectal Cancer-Promises and Challenges

Abstract

Colorectal carcinoma (CRC) is the most lethal and common form of cancer in the world. It was responsible for almost 881,000 cancer deaths in 2018. Approximately 25% of cases are diagnosed at advanced stages with metastasis-this poses challenges for effective surgical control and future tumor-related mortality. There are numerous diagnostic methods that can be used to reduce the risk of colorectal carcinoma. Among these, targeted nanotherapy aims to eliminate the tumor and any metastasis. Active targeting can increase the effectiveness and quantity of drugs delivered to the target site. Antibodies that target overexpressed receptors on cell surfaces and indicators are coupled with drug-loaded carriers. The major target receptors of chemotherapeutic drugs delivery include VEGFR, EGFR, FGFR, HER2, and TGF. On account of its major and diverse roles in cancer, it is important to target EGFR in particular for better tumor selection, as EGFR is overexpressed in 25 to 82% of colorectal carcinoma cases. The EGFR monoclonal immunoglobulins cetuximab/panitumumab can thus be used to treat colorectal cancer. This review examines carriers that contain cetuximab-conjugated therapeutic drugs as well as their efficacy in anticancer activities.

Keywords: EGFR; cetuximab; colorectal cancer; nanocarriers; nanomedicine.

Figure 1

The mechanism of active and passive targeting by nanocarriers.

Figure 2

Structure of EGFR receptor.

Figure 3

Major anti-tumor mechanisms by which cetuximab acts (1) and (2) are the mechanisms that normally take place in the absence of cetuximab i.e., binding of the ligands to the EGFR monomers, induction of receptor dimerization, and downstream signalling pathways. (3) Cetuximab binds to domain III of EGFR. (4) Receptor internalization mediated by cetuximab and inhibition of downstream signalling pathways. (5) Fc segment of cetuximab binds to natural killer cells and induces ADCC. (6) G1 cell cycle arrest. (7) inhibition of angiogenesis. (8) Induction of apoptosis.