Drug-Resistant Breast Cancer: Dwelling the Hippo Pathway to Manage the Treatment.

Breast cancer can be categorized as a commonly occurring cancer among women with a high mortality rate. Due to the repetitive treatment cycles, it has been noted that the patients develop resistance towards the chemotherapeutic drugs and remain unresponsive towards them. Therefore, many researchers are studying various signaling pathways involved in drug resistance for cancer treatment to overcome the obstacle. Hippo signaling is a widely studied pathway involved in tumor progression and controlling cell proliferation. Hence, understanding the aspects of the gene involved Hippo pathway would provide an insight into the mechanism behind the resistance and result in the development of new treatments. Here, we review the Hippo signaling pathway in humans and how the expression of different components leads to the regulation of resistance against some of the common chemo-drugs used in breast cancer treatment. The article will also discuss the chemotherapeutics that became ineffective due to the resistance and the mechanism following the process.

Assessment of proarrhythmic activity of chloroquine in in vivo and ex vivo rabbit models.

OBJECTIVES: To evaluate the prolongation of ventricular repolarization and proarrhythmic activity of antimalarial drug chloroquine in two rabbit proarrhythmia models viz., in vivo α1 adrenoceptor-stimulated anesthetized rabbit and ex vivo isolated Langendorff rabbit heart using clofilium as standard proarrhythmic agent. MATERIALS AND METHODS: In the in vivo model, three groups of rabbits, anesthetized by pentobarbitone sodium and α-chloralose, sensitized with α1 agonist methoxamine followed by either continuous infusion of saline (control) or clofilium (3 mg/kg) or chloroquine (21 mg/kg) for 30 min. In ex vivo model, rabbit hearts were perfused with clofilium (10 µM) or chloroquine (300 µM) continuously after priming along with methoxamine, acetylcholine chloride and propranolol hydrochloride. RESULTS: In these models, prolongation of repolarization during α1-adrenoceptor stimulation produced early after depolarization (EAD) and Torsade de pointes (TdP). Saline infusion did not induce any abnormality in the animals. Clofilium caused expected changes in the electrocardiogram in both the models including TdP (50.0% in in vivo and 66.67% in ex vivo). Chloroquine caused decrease in heart rate and increase in the corrected QT (QTc) interval in both the models. Further, apart from different stages of arrhythmia, TdP was evident in 33.33% in ex vivo model, whereas no TdP was observed in in vivo model. CONCLUSIONS: The results indicated that proarrhythmic potential of chloroquine and clofilium was well evaluated in both the models; moreover, both the models can be used to assess the proarrhythmic potential of the new drug candidates.