The Pharmacogenetics behind Polymorphisms of the Immunoglobin G Fragment C Receptor and Efficacy of Monoclonal Antibody Treatments for Different Cancers.
MetadataShow full item record
The vertebrate immune system has evolved to become particularly good at protecting an organism from extrinsic pathogens such as bacterial and fungal infections. Today the cutting edge of medicine is trying to manipulate the immune system of cancer patients into attacking their own cancerous cells. This can be facilitated through the use of monoclonal antibody (mAb) treatments targeted towards tumor cell receptors or ligands that are responsible for the flourishing of particular types of cancers. It has been postulated that mAb treatments may work by stimulating the patient’s immune system to kill cancerous cells through antibody-dependent cell-mediated cytotoxicity (ADCC). This process may be responsible in part for the efficacy of these antibody treatments. Curiously, the response of tumors to mAbs varies amongst patients. One hypothesis for this stratification amongst patients is that polymorphisms within immune cell receptor genes can influence the affinity of the immune cells to the mAb and hence may control how well the immune system attacks cancer cells. Our study focuses on the relationship between the efficacy of monoclonal antibodies currently used in the clinic for treatment of solid and hematological cancers and polymorphism of the immunoglobin G fragment C receptor. Using 14 studies as evidence, it appears that there is not a clear cut answer for a relationship between FcγR polymorphisms and efficacy of mAb treatment. Perhaps this is due to the many different kinds of combinational therapies which are used in the clinic. However the trend seems to be that the FcγRIIIa-158V/V genotype does improve response to treatment and can provide a longer progression-free survival (PFS) of lymphoma and breast cancer patients. For the FcγRIIa-131 polymorphism, it appears H-carriers can have a longer median PFS than other patients regardless of tumor response status. We did find that mAb treatments do not correspond with FcR polymorphisms in patients with chronic lymphocytic leukemia. Furthermore we find that “stable disease” classification can be linked with longer PFS and could therefore potentially be considered a good prognostic indicator for clinical benefit. Further research needs to be done, potentially with larger patient cohorts and proper controls to come to a definitive answer on if the FcR polymorphisms are a useful predictor of tumor response to mAb treatment.