Chronic Neurological Disorders: Genetic and Epigenetic Markers for Monitoring of Pharmacotherapy.

INTRODUCTION: Chronic neurological diseases are a major cause of mortality and morbidity in the world. With increasing life expectancy in the developing world, the incidence and prevalence of these diseases are predicted to rise even further. This has also contributed to an increase in disability-adjusted life years (DALYs) for noncommunicable diseases. Treatment for such diseases also poses a challenge with multiple genetic and epigenetic factors leading to a varied outcome. Personalization of treatment is one way that treatment outcome/prognosis of disease can be improved, and pharmacogenomics plays a significant role in this context. METHODOLOGY: This article reviewed the evidence pertaining to the association of genetic and epigenetic markers with major neurological disorders like multiple sclerosis (MS), Alzheimer's disease (AD), and Parkinson's disease (PD), which are a major source of burden among neurological disorders. Types of studies included are peer-reviewed original research articles from the PubMed database (1999-2018). RESULTS: This study compiled data regarding specific genetic and epigenetic markers with a significant correlation between the clinical diagnosis of the disease and prognosis of therapy from 65 studies. In a single platform, this review highlights the clues to some vital questions, such as why interferon beta (IFN-ß) therapy fails to improve symptoms in all MS patients? why cholinesterase inhibitors fail to improve cognitive impairment in a subset of people suffering from AD? or why some individuals on levodopa (L-DOPA) for PD suffer from side-effects ranging from dyskinesia to hallucination while others do not? CONCLUSION: This article summarizes the genetic and epigenetic factors that may either require monitoring or help in deciding future pharmacotherapy in a patient suffering from MS, AD, and PD. As the health care system develops and reaches newer heights, we expect more and more of these biomarkers to be used as pharmacotherapeutic outcome indicators.

Acalabrutinib in management of chronic lymphocytic leukemia: An Indian perspective.

The treatment landscape of chronic lymphocytic leukemia (CLL) has witnessed immense changes in the past decade. Several newer target therapies and their combinations with anti-CD 20 therapies have got approval for management of CLL in the treatment-naïve and relapsed/refractory setting. Also, the availability of newer diagnostic techniques has helped differentiate the disease into high- and low-risk CLL which acts not just as a prognostic marker but also helps decide the best drug management that can be administered to the patients. Targeted therapy has largely overtaken chemoimmunotherapy in the management of CLL, except for a small subset of the population (young and fit with IGHV mutation). However, with targeted therapy, there is also an issue of previously uncommon treatment-emergent adverse events, the duration of therapy, and financial toxicity. The aim of this review article is to gather results from all landmark CLL trials and discuss the feasibility of incorporating Acalabrutinib in the CLL landscape from an Indian perspective.

Antibody-drug conjugates, cancer immunotherapy, and metronomic chemotherapy as novel approaches in cancer management.

Treatment of cancer is a major challenge even though the pathophysiology is becoming clearer with time. A number of new chemical entities are developed to target cancer growth inhibition, but the targeted delivery of these products still needs novel research. This is of utmost importance not only for higher efficacy but also for a reduction in systemic toxicity and cost of treatment. Although multiple novel targets and molecules are being researched, most of them could not pass the regulatory approval process, due to low benefit-risk ratio and lack of target specificity. Failure of a majority of these drugs was in part due to their superiority claimed via surrogate markers. Despite these, currently, more than 100 chemotherapeutic agents are in practice. This review paper discusses in detail the molecular basis, drug discovery, and pros and cons over conventional treatment approaches of three novel approaches in cancer therapy, i.e., (i) antibody-drug conjugates, (ii) cancer immunotherapy, and (iii) metronomic chemotherapy. All the drugs developed using these three novel approaches were compared against the established treatment regimens in clinical trials with clinical end points, such as overall survival, progression-free survival, and quality of life.