Solai Elango Damodaran

Purpose Tamoxifen is used in the treatment of breast cancer to prevent recurrences. It is converted to its active metabolite endoxifen by CYP2D6 enzyme. This study was conducted to evaluate the influence of CYP2D6 genetic polymorphisms on the recurrence of breast cancer in patients receiving treatment with tamoxifen as an adjuvant hormonal therapy. Methods Breast cancer patients (n = 141) on adjuvant tamoxifen and not on any concomitant CYP2D6 inhibitors were recruited for the study. Patient characteristics and treatment history were obtained. Five milliliters of venous blood was collected for genotyping CYP2D6 alleles *1, *2, *4, *5 and *10. CYP2D6 activity score was calculated to determine the phenotype based on genotype. The activity scores were compared between patients with recurrence and patients with no recurrence of breast cancer. Results Of the 141 patients recruited for the study, genotyping was done for 132 of them. CYP2D6 activity score ≤0.5 is associated with a statistically significant increased risk of recurrence (OR—12.37; 95 % CI—3.23, 47.33; p < 0.001) and shorter recurrence free survival (52.68 ± 10.58 months (mean ± SEM); p < 0.001) as was shown in Kaplan–Meir survival estimates, when compared to activity score ≥1. The hazard ratio for activity score ≤0.5 is 7.29 (p < 0.001) when compared to activity score ≥1. Analysis of known estrogen receptor positive patients also showed statistically significant increased risk of recurrence and shorter recurrence free survival in patients with CYP2D6 activity score ≤0.5. The Cox proportional hazard ratio was found to be 7.15 (p = 0.006) for activity score ≤0.5. Conclusion Reduced CYP2D6 activity is associated with poor treatment outcomes, in terms of increased risk of recurrence and shorter recurrence free survival, in breast cancer patients on adjuvant tamoxifen therapy.

J Pharmacol Pharmacother, Official publication of InPharm Association, India

Malaria is the third leading cause of death due to infectious diseases affecting around 243 million people, causing 863,000 deaths each year, and is a major public health problem. Most of the malarial deaths occur in children below 5 years and is a major contributor of under-five mortality. As a result of environmental and climatic changes, there is a change in vector population and distribution, leading to resurgence of malaria at numerous foci. Resistance to antimalarials is a major challenge to malaria control and there are new drug developments, new approaches to treatment strategies, combination therapy to overcome resistance and progress in vaccine development. Now, artemisinin-based combination therapy is the first-line therapy as the malarial parasite has developed resistance to other antimalarials. Reports of artemisinin resistance are appearing and identification of new drug targets gains utmost importance. As there is a shift from malaria control to malaria eradication, more research is focused on malaria vaccine development. A malaria vaccine, RTS,S, is in phase III of development and may become the first successful one. Due to resistance to insecticides and lack of environmental sanitation, the conventional methods of vector control are turning out to be futile. To overcome this, novel strategies like sterile insect technique and transgenic mosquitoes are pursued for effective vector control. As a result of the global organizations stepping up their efforts with continued research, eradication of malaria can turn out to be a reality.