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Clinical Oncology 2020: Role of Pharmacogenetic monitoring in Oncology: Literature review - Karunrat Tewthanom, Sikpakorn University NakhonPathom, TH

Karunrat Tewthanom

The trend in Pharmacogenomic knowledges has been widely popular and use in many fields, including oncology.  The literature review found that there are many studies about the useful of pharmacogenomic monitoring in patients with cancer, both for therapeutics and adverse effect monitoring. An example of Pharmacogenomics in therapeutics monitoring is breast cancer, the HER 2 positive patients will be have more chance to achieve goal of therapy. In safety monitoring circumstance for example in chronic myeloid leukemia who receive tyrosine kinase inhibitor, with should be screen for UGT1A1 polymorphism because it impacts on adverse events for nilotinib.  

The transition from development of standard cytotoxic chemotherapies to highly targeted agents and immunotherapies has resulted in the current breadth of treatment options available.3 Further, increased numbers of targeted therapies are receiving accelerated drug approval alongside companion diagnostic assays, which are critical in identifying predictive biomarkers that allow for a personalized approach to therapy selection.4 A highly focused attack on targetable driver mutations has not only resulted in superior response rates and overall survival (OS) compared to traditional, nontargeted chemotherapy but has also allowed for more rapid time to drug approval, ensuring timely access of life-prolonging drugs to cancer patients in dire need of more options. More recently, there has been a transition in cancer treatment to increased utility of immunotherapies and various combinations of cytotoxic chemotherapies/targeted agents with immunotherapies. This ever expanding armamentarium of cancer therapies means greater reliance on biomarkers to help clinicians decide which therapies a particular patient may benefit from.

Pharmacogenetics – the study of how genes influences drug response – provides the opportunity to stratify patients into those likely to respond or not respond to therapy, or those likely to experience or not experience toxicity.6 The term “pharmacogenomics” is commonly used in the literature to define the broader field of genomics and genome-wide associations with drug response. Genomics cancer research provides the ability to analyze both the patient’s (germline) and the tumor’s (somatic) DNA. While germline DNA is readily obtained via a blood sample or buccal swab, somatic DNA is primarily obtained via tumor biopsy and is therefore a more invasive collection procedure and is subject to sample selection. Clinically relevant (inherited) germline variations in the host may be valuable in determining the pharmacokinetic disposition of drugs and drug response (in addition to identification of disease-susceptibility genetic variants), while somatic mutations found within the tumor are acquired and are particularly useful in assessing the pharmacodynamic effects of a drug and ultimately tumor response.

Cancer sequencing efforts may capture germline information from matched normal tissue or blood samples, which may be informative for drug/dose selection or disease susceptibility, and somatic mutations, which primarily drive selection of targeted cancer therapies.7 These efforts will generate tremendous amounts of data, and clinicians must be prepared to interpret and utilize this information to optimize cancer therapeutics. A major focus on bioinformatics to readily retrieve actionable information and evidence-based guidelines to translate results into prescribing decisions will be key in the advancement of molecular profiling and selection of targeted therapies.

Conclusion & Significance: From the literature review implies that pharmacogenetic monitoring has more important in oncology. It is useful for both therapeutic and safety monitoring.