▶️ Can Fc receptor polymorphisms affect drug efficacy or toxicity?
– Yes, Fc receptor polymorphisms can affect drug efficacy or toxicity. Fc receptors are proteins that bind to the Fc region of antibodies and modulate the function of immune cells. Fc receptors can be classified into activating and inhibitory types, depending on their signaling motifs and functions. Activating Fc receptors trigger pro-inflammatory pathways and enhance the immune response, while inhibitory Fc receptors dampen the immune response and prevent excessive inflammation.
– Fc receptor polymorphisms are genetic variations in the genes encoding Fc receptors that can affect their binding ability to different classes and subclasses of antibodies. Fc receptor polymorphisms can influence the pharmacokinetics and pharmacodynamics of drugs that are based on antibodies, such as monoclonal antibodies (mAbs) and immune checkpoint inhibitors (ICIs). These drugs can interact with Fc receptors on various immune cells, such as natural killer (NK) cells, macrophages, eosinophils, and neutrophils, and modulate their activity and function.
– Fc receptor polymorphisms can have different effects on drug efficacy or toxicity depending on the type of drug, the target antigen, the immune cell, and the disease. For example, some studies have reported that FcγRIIa (H131R) and FcγRIIIa (V158F) polymorphisms can affect the response to mAbs that target tumor antigens, such as trastuzumab (anti-HER2), rituximab (anti-CD20), and cetuximab (anti-EGFR). These polymorphisms can influence the antibody-dependent cellular cytotoxicity (ADCC) mediated by NK cells or macrophages against tumor cells.
– Other studies have suggested that FcγRIIb (I232T) polymorphism can affect the response to ICIs that target immune checkpoints, such as ipilimumab (anti-CTLA-4), nivolumab (anti-PD-1), and atezolizumab (anti-PD-L1). This polymorphism can influence the regulation of T cell activation and proliferation by inhibitory FcγRIIb on B cells or dendritic cells
– Therefore, Fc receptor polymorphisms can be potential biomarkers for predicting or optimizing the response to antibody-based drugs in cancer patients. However, more studies are needed to validate the clinical relevance and applicability of these polymorphisms in different settings and populations.
