Selecting Targets for Tumor Imaging: An Overview of Cancer-Associated Membrane Proteins

Abstract

Tumor targeting is a booming business: The global therapeutic monoclonal antibody market accounted for more than $78 billion in 2012 and is expanding exponentially. Tumors can be targeted with an extensive arsenal of monoclonal antibodies, ligand proteins, peptides, RNAs, and small molecules. In addition to therapeutic targeting, some of these compounds can also be applied for tumor visualization before or during surgery, after conjugation with radionuclides and/or near-infrared fluorescent dyes. The majority of these tumor-targeting compounds are directed against cell membrane-bound proteins. Various categories of targetable membrane-bound proteins, such as anchoring proteins, receptors, enzymes, and transporter proteins, exist. The functions and biological characteristics of these proteins determine their location and distribution on the cell membrane, making them more, or less, accessible, and therefore, it is important to understand these features. In this review, we evaluate the characteristics of cancer-associated membrane proteins and discuss their overall usability for cancer targeting, especially focusing on imaging applications.

Evaluation of EphA2 and EphB4 as Targets for Image-Guided Colorectal Cancer Surgery

“…In theory any up-regulated protein present in cancer tissue could be a potential target for IGOS, but in practice the proteins expressed on the surface of tumor cells are the best candidates [3]. Cheever and colleagues ranked EphA2 as one of the highest cell surface antigens for cancer treatment [4].…”

“…Besides the quality of the camera system, the effectiveness of this technique relies mainly on the choice of the targeted tumor protein. Receptors and adhesion molecules upregulated on the surface of tumor cells are the best candidates for targeted cancer imaging, but the ideal protein for colorectal cancer imaging has not yet been identified [3]. Cell surface-associated proteins such as MUC1, EGFR, HER2, PSMA, and CEA are highly ranked on the NCI prioritization list of cancer antigens and are amongst the most pursued biomarkers for imaging 2 of 8 [4].…”

Introducing fluorescence guided surgery into orthopedic oncology: A systematic review of candidate protein targets for Ewing sarcoma

“…Generally they are transmembrane receptors that consist of three parts: an intracellular domain interacting with the cytoskeleton, a transmembrane domain and an extracellular domain that interact with either other CAMs or with the extracellular matrix. CAMs form a large and diverse group of proteins, and most of the members belong to either the immunoglobulin superfamily, or to the families of integrins, cadherins or selectins …”

“…Therefore, many oncologic targets have been explored and indeed sub‐millimeter sized tumor nodules could be detected in animal models . With the first tumor‐targeting clinical trial performed in 2011 by van Dam et al, fluorescence guided surgery (FGS) is at the doorstep of clinical translation to oncologic surgery, and many targets are being explored using numerous detection platforms like antibodies, peptides, and RNA aptamers …”

“…When defining a potential biomarker for targeting, the following characteristics are of utmost importance: extracellular biomarker localization, expression pattern, tumor‐to‐healthy tissue ratio, the percentage of positive tumors, reported successful use of the biomarker in in vivo imaging studies and internalization …”