Immunopharmacogenomics in Cancer Management

With the unavoidable progress of genomics technologies, “one size fits all” strategy has switched to individual-specific treatment approaches. Hence pharmacogenomics-based personalized cancer medicine has emerged. Promising treatment option immunotherapy includes either “take the brakes off immune system (i.e., checkpoint blockade therapy) or the use of immune cells expanded in an in vitro tumor-free environment’’. Both options have been varied and included unpredictable results. Combination of cancer immunotherapy and pharmacogenomics applications may contribute to solve the complexity of outcome prediction and variations between individuals receiving the same immunotherapeutic treatment. To enhance the tumor immunity and determine cancer patients who response to immunotherapy, classification based on gene polymorphisms in key immunoregulatory molecules including antigen-presenting molecules, immunoglobulins and their receptors, cytokine/chemokines and their receptors, adhesion and costimulatory molecules, toll-like receptors, and intracellular signaling molecules plays a vital role in redirecting or modulating the function of immune cells. Therefore, polymorphisms in immunoregulatory molecules and their impact on immunotherapeutic outcome should be considered in cancer management

Polymorphisms in Pharmacogenetics of Personalized Cancer Therapy

Therapy process of personalized cancer management covers surgery, chemotherapy, radiation therapy and targeted therapies. The choice of cancer chemotherapeutic agents and doses depends upon the location and stage of tumor, as well as the general state of the patient. On the chemotherapy, radiotherapy, and targeted therapy processes, pharmacogenetics offers customized solutions according to the personal genetic information. Especially for clinicians, genetic information obtained from polymorphism-based pharmacogenetic tests is highly crucial for the better prediction ability of drug response and life-threatening toxic reactions due to the narrow therapeutic index of cancer chemotherapeutic agents. Pharmacogenotyping utilizes different examination strategies, such as single nucleotide polymorphism analysis, somatic/germline mutation analysis and partial/full genome sequencing. The promising effect of pharmacogenetics on the solving of the individual variability in drug response and toxic reactions is being observed with the accumulation of the information that unravel the human genomic variations from large-scale population and multi-parameter-based pharmacogenetic studies of the post-genomic era. Polymorphisms contribute wide variations in human genome and may define how individuals respond to medications, either by changing the pharmacokinetics and pharmacodynamics of drugs or by altering the cellular response to therapeutic agents. To define the effect of polymorphisms on the targets of chemotherapeutics is necessary for the prediction of altered pharmacokinetics of therapeutic agents