Targeted therapy for colorectal cancer metastases: A review of current methods of molecularly targeted therapy and the use of tumor biomarkers in the treatment of metastatic colorectal cancer

Abstract

Despite recent advances in the management of colorectal cancer, metastatic disease remains challenging, and patients are rarely cured. However, a better understanding of the pathways implicated in the evolution and proliferation of cancer cells has led to the development of targeted therapies, that is, agents with action directed at these pathways/features. This approach is more specific to cells within which these pathways, such as epidermal growth factor receptor (EGFR), are overactive; this is in contrast to the relatively indiscriminate mechanism by which cytotoxic chemotherapy tends to affect rapidly dividing cells, regardless of their role. Although factors unique to a given patient, such as the location of the primary tumor (sidedness) or the presence of mutations that confer resistance, may limit the utility of these agents, targeted therapies are now a part of the treatment paradigm for metastatic colorectal cancer, and survival outcomes have significantly improved. This review provides an overview of the role of targeted therapy in the management of patients with colorectal cancer metastases as well as a discussion of issues in patient selection, with a focus on inhibitors of angiogenesis, EGFR‐targeted therapy, BRAF mutation–targeted therapies, and other novel strategies, including immunotherapy.

Colorectal cancer statistics, 2020

“…Headway in the treatment of metastatic disease, including improved surgical techniques, increased cancer‐directed surgery, advances in the treatment of liver metastases, and the development of targeted therapies, is evident in survival gains for these patients in recent decades. For example, the 2‐year relative survival rate for patients diagnosed with distant‐stage disease increased from 21% during the mid‐1990s to 37% during 2009 through 2015, with a larger improvement for rectal cancer (from 22% to 41%) than for colon cancer (from 21% to 36%).…”

What is New in the 2019 World Health Organization (WHO) Classification of Tumors of the Digestive System: Review of Selected Updates on Neuroendocrine Neoplasms, Appendiceal Tumors, and Molecular Testing

“…RAS mutational analysis helps to select patients with metastatic CRC for anti-EGFR therapy. 80,81 Although BRAF mutations are only found in 7% to 10% of patients with CRC, their presence conveys a very poor prognosis with a median survival of less than 12 months. The presence of BRAF mutations is also used to exclude Lynch syndrome.…”

Innate Lymphoid Cells in Colorectal Cancers: A Double-Edged Sword

“…Multiple treatment approaches have been developed in an endeavor to provide curative outcomes for patients. These include targeting oncogenic drivers (RAS, BRAF), receptors of growth factors (EGFR) or pathways involved in angiogenesis such as VEGFR (15). As an example, Bevacizumab, a human IgG1 antibody directed against VEGF-A, increased patient overall and progression-free survival when combined with chemotherapies (14,16,17).…”