Ten Years of Experience Support Pharmacogenetic Testing to Guide Individualized Drug Therapy

Precision medicine utilizing the genetic information of genes involved in the metabolism and disposition of drugs can not only improve drug efficacy but also prevent or minimize adverse events. Polypharmacy is common among multimorbid patients and is associated with increased adverse events. One of the main objectives in health care is safe and efficacious drug therapy, which is directly correlated to the individual response to treatment. Precision medicine can increase drug safety in many scenarios, including polypharmacy. In this report, we share our experience utilizing precision medicine over the past ten years. Based on our experience using pharmacogenetic (PGx)-informed prescribing, we implemented a five-step precision medicine protocol (5SPM) that includes the assessment of the biological–clinical characteristics of the patient, current and past prescription history, and the patient’s PGx test results. To illustrate our approach, we present cases highlighting the clinical relevance of precision medicine with a focus on patients with a complex history and polypharmacy.

Microbial Community Profiling Distinguishes Left-Sided and Right-Sided Colon Cancer

The difference between left- and right-sided colon cancer has become the focus of global attention, and researchers have found differences in the morbidity, molecular biological characteristics, and response to targeted drug therapy between left- and right-sided colon cancer. Therefore, the identification of more effective predictive indicators is critical for providing guidance to future clinical work. We collected samples from different colon sites and regions and analyzed the identities and distributions of differentially expressed species in the microbiota in the left and right sides of the colon to better explore the pathogenesis of colon cancer and provided a basis for individualized drug therapy. We collected samples from different regions in the body of 40 patients with colon cancer, including stool and tissues. The Subjects were classified into four groups, and this classification was mainly based on the colon cancer distribution. The microbiota composition of the left-sided and right-sided colon samples was assessed by specifically amplifying the V3-V4 region of the 16S rDNA gene from DNA extracts from the samples. These amplicons were examined by Illumina HiSeq 2500 sequencing. The microbial taxa in the left-sided colon samples are more abundant than those in the right-sided colon samples. The flora in the left-sided colon samples, such as Clostridium perfringens and Fusobacterium nucleatum, might be associated with VEGF expression and are more likely to promote colon cancer. The microbiota distribution in the right-sided colon samples is less invasive and harmful and particularly rich in Bifidobacterium dentium. In addition, Streptococcus, which is the target of EGFR, was found to be expressed in both the left- and right-sided colon samples but was found at a higher level in the left-sided colon samples. Additionally, the differential pathways involved in the left-sided colon samples mainly mediate DNA damage, methylation, and histone modifications, whereas those in the right-sided colon samples are dominated by DNA synthesis. The comparison of only the geographical differences revealed a significant difference in the distribution of the microbial population. The adherent microbiota composition and structural changes between the left- and right-sided colon samples might contribute to the development of colon cancer, lead to different morbidities, and further affect the prognosis of patients and their sensitivity to targeted drugs. Therefore, the identification of the differential flora in the colon could be used as an indicator for predicting the occurrence and development of colon cancer, which is also beneficial for future individualized drug therapy.

The Emerging Focus on Pharmacogenomics

Drugs are designed to treat medical conditions for the general population. Idiosyncratic reactions to drugs are determined by the individual’s respective genetic variations that direct effectiveness and side effects. Adverse drug reactions rank within the top ten leading causes of death in the developed world. The field of pharmacogenomics has advanced in the last fifty years, picking up significant momentum with recent biotechnological developments that allow scientists to investigate the human genome and provide individualized drug therapy that will increase the efficacy of drugs and decrease the incidence of adverse drug reactions. Pharmacogenomics has reached a milestone in making personalized medicine accessible and effective. The medical community shares this responsibility for the emerging focus on pharmacogenomics with regulatory agencies and bioinformatics specialists as they struggle to streamline vast libraries of information and reconcile public and regulatory approval on this critical path to the next level of health care.

Conceptual study for long-term monitoring of chemotherapeutic induced cell reactions by ESPI

During the last years, various approaches on an individualized drug therapy for benign cells have been researched. However, due to the complex topic a universal approach has not been found up until this point. Commonly, the effect of cytotoxic drugs on benign cells is in most cases the same compared to regular cells while the actual effect on patient still can't be predicted. In order to reduce unwanted side effects or unspecific drug reactions a test system for patients which allows to analyse the interaction between cytotoxic agents and the targeted cells is needed. Furthermore, this should also include an adequate measurement system which is capable to work in a natural environment and without any additional preparation. In terms of this work, a first proof of concept with different benign cells and cytotoxic agents is presented while monitoring the obtained displacement using electronic speckle pattern interferometry (ESPI).

Indigenous methods for assessment of important aspects in undergraduates on pharmacology and therapeutics: a preliminary study

Background: In pharmacology and therapeutics tutorial in current times is being disliked by most undergraduates. On the other hand, the important exercises related to analytical skill development, problem based exercise, rational use of medicine and individualized drug therapy need to be emphasize more in UG teaching and learning techniques.Methods: In the form of active learning we have framed CME pattern of conducting some important exercises including four above mentioned to facilitate the ability to think, feel or do the task which may be acceptable to the students better than or equivalent to tutorials.Results: We observed that 2 out of 8 willing participants scored higher than others in CME activity as well as terminal exams the other 2 scored borderline higher in CME activity than their score in terminal exams. Another 4 scored better in the terminal examinations as compared to CME activity.4 out of 8 i.e. 50% participants have shown acceptability as well as better performance in these exercises.Conclusions: All of these exercises are not in the curriculum/syllabus and there is no incentive of internal assessment on these. If these exercises are made mandatory, as it is the need of the hour, these can benefit the learner possibly by the way of change in their cognitive structure, keeping tutorials intact or removing them from syllabus.