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.

NK Cell-Based Immunotherapy in Colorectal Cancer

“…Treatment with anti-TAA mAbs can induce tumor cell death by several mechanisms, such as directly inducing tumor apoptosis or via ADCC, that is, mediated by CD16 engagement with IgG-opsonized tumor cells. Indeed, the efficacy of an anti-TAA mAb largely employed in the treatment of metastatic CRC, i.e., anti-EGFR (known by the commercial names Cetuximab or Panitumumab or Necitumumab [ 61 ]) also relies on enhanced NK-mediated killing via ADCC ( Figure 2 a). The epidermal growth factor receptor (EGFR; ErbB-1; HER1 in humans), a transmembrane tyrosine kinase receptor, affects cell adhesion, survival and proliferation and is overexpressed in most CRC (75%) and is associated with poor prognosis.…”

Engaging innate immunity for targeting the epidermal growth factor receptor: Therapeutic options leveraging innate immunity versus adaptive immunity versus inhibition of signaling

“…Broadly, there are two main types of therapies approved to target EGFR: small molecule tyrosine kinase inhibitors (TKIs) and anti-EGFR antibodies. TKIs act to inhibit EGFR kinase activity, thus attenuating downstream signal transduction ( 22 ); whereas anti-EGFR antibodies serve to block ligand binding to the extracellular portion of EGFR leading to inhibition of downstream signaling, but also have the capacity to leverage cytotoxic immune cells to induce anti-tumor antibody-dependent cellular cytotoxicity (ADCC) ( 23 , 24 ). Both types of therapy have demonstrated efficacy in subsets of patients with certain tumor types, with TKIs exhibiting efficacy in, for example, NSCLC with EGFR -activating mutations ( 25 ), and anti-EGFR antibodies in tumor types such as metastatic CRC (mCRC) ( 9 ), and SCCHN ( 26 ).…”

Is red blood cell distribution width a prognostic factor for colorectal cancer? A meta-analysis

“…Among them, CRC was the third most common cancer in males and the second in females (2). The treatments of CRC include surgery, chemotherapy, radiotherapy, surgery, targeted therapy and immunotherapy (3)(4)(5)(6)(7)(8). Nowadays, radical surgery is the cornerstone treatment of CRC (9,10), which not only can treat cancer, but also help in the improvement of some comorbidities (11,12).…”