HER-2 GENE, RECEPTORS AND DRUG TARGET: A SYSTEMATIC REVIEW

The discovery and identification of the human epidermal growth factor receptor 2 (HER's-2) genes, have led to a better understanding of breast tumour biology. A member of the epidermal growth factor receptor family, it is a potent mediator of cellular growth and proliferation in malignant epithelial cells. Amplification or over expression of HER-2 occurs in approximately 15–30 % of breast cancers and 10–30 % of gastric/gastroesophageal cancers and serves as a prognostic and predictive biomarker. Treatment with HER-2 targeted monoclonal antibody, trastuzumab dramatically improved outcome in patients with breast malignancy. This promising approach led to the development of pertuzumab, ado-trastuzumab emtansine and lapatinib. The development of drug resistance and disease progression due to alternate signalling remained a real therapeutic challenge. Several research studies are currently focused on inhibition of onco-proteins, kinases and growth factors linked to HER-2 positive breast cancers. The success of immune checkpoint modulators and vaccines in preliminary studies describes the role of tumour immunity. Apart from its role in the pathogenesis of various cancers, HER-2 directed therapeutic approach has brought about a revolutionary change in terms of time to progression and survival rates in breast cancers.Keywords: ErbB-2 signalling, Targeted approach, Trastuzumab, Drug resistanc

A retrospective study of serious adverse drug reactions and associated risk factors in a tertiary care hospital

Background: Serious adverse drug reactions (ADRs) cause physical, psychological and economic harm to patients and society. This study was undertaken to understand serious ADRs in a tertiary care hospital and risk factors associated with it.Methods: The serious adverse reactions that occurred over a one-year period were assessed. The serious adverse drug reactions, action taken, outcome, predictability, suspect drug, causality, patient demographics and risk factors for the reaction was collected. Chi-square test was applied for observing relationships of predisposing factors for serious ADRs.Results: Out of a total of 984 reported adverse drug reactions, 94 (9.55%) were serious. Hematological disorders (41.05%) were the common serious ADRs followed by electrolyte disturbances (18.94%). Anticancer agents were the suspect drugs for majority of serious ADRs. Serious ADRs contributed to 39 (0.05%) admissions in the hospital. Recovery occurred in 97.87% of the patients. The causality was possible in 91.48% (n=86) and probable in 8.51% (n=8) of the serious adverse drug reactions. Males, patients even with a single concomitant disease and those with more than 2 concomitant medications were at increased risk (p<0.05) for developing serious ADRs.Conclusions: Serious ADRs are a significant problem in health care. Measures should be taken to detect and treat them at the earliest to reduce suffering of the patient