The Current State of Targeted Agents in Rectal Cancer

Abstract

Targeted biologic agents have an established role in treating metastatic colorectal cancer (CRC), and the integration of targeted therapies into the treatment of CRC has resulted in significant improvements in outcomes. Rapidly growing insight into the molecular biology of CRC, as well as recent developments in gene sequencing and molecular diagnostics, has led to high expectations for the identification of molecular markers to be used in personalized treatment regimens. The mechanisms of action and toxicities of targeted therapies differ from those of traditional cytotoxic chemotherapy. Targeted therapy has raised new insight about the possibility of tailoring treatment to an individual's disease, the assessment of drug effectiveness and toxicity, and the economics of cancer care. This paper covers the last decade of clinical trials that have explored the toxicity and efficacy of targeted agents in locally advanced and metastatic CRC and how their role may benefit patients with rectal cancer. Future efforts should include prospective studies of these agents in biomarker-defined subpopulations, as well as studies of novel agents that target angiogenesis, tumor-stromal interaction, and the cell signaling pathways implicated in rectal cancer.

Germline and Somatic Pharmacogenomics to Refine Rectal Cancer Patients Selection for Neo-Adjuvant Chemoradiotherapy

“…EGFR was demonstrated to have a pivotal role in LARC as well as in the colorectal cancer carcinogenesis (Toffoli et al, 2007;Kim and Eng, 2012). Moreover, EGFR and related pathways, are activated by ionizing radiation, and have been suggested to be a druggable target for the neo-adjuvant treatment of LARC.…”

Proactive strategies for regorafenib in metastatic colorectal cancer: implications for optimal patient management

“…The development of biologics to specifically target variable steps in carcinogenesis and metastasis have been incorporated into first- and second-line mCRC treatment strategies, broadening the spectrum of therapies for this disease 3. Standard treatments include cytotoxic regimens with fluoropyrimidines, oxaliplatin, or irinotecan used in combination or sequentially plus monoclonal antibodies targeting vascular endothelial growth factor (VEGF) or epidermal growth factor receptor (EGFR) 4.…”

“… 1 , 2 The development of biologics to specifically target variable steps in carcinogenesis and metastasis have been incorporated into first- and second-line mCRC treatment strategies, broadening the spectrum of therapies for this disease. 3 Standard treatments include cytotoxic regimens with fluoropyrimidines, oxaliplatin, or irinotecan used in combination or sequentially plus monoclonal antibodies targeting vascular endothelial growth factor (VEGF) or epidermal growth factor receptor (EGFR). 4 Chemotherapy combinations with bevacizumab that specially target VEGF-A or combinations with cetuximab (an EGFR inhibitor monoclonal antibody) for patients with a KRAS wild-type tumor are now standard first-line treatment options.…”

Regorafenib: start low and go slow

“…A backbone chemotherapy regimen can now be combined with bevacizumab or cetuximab/panitumumab for patients with KRAS/NRAS wild-type tumors [1,2]. These combinations can be swapped in the second line setting depending on the initial regimen chosen [3].…”