Assessment of anti-cancer drug induced cardiotoxicity in human induced pluripotent stem cell (hiPSC) derived cardiomyocytes using a multiparametric approach

Cardiotoxicity is a major cause of attrition during (pre)clinical anticancer drug development [1] and a growing concern with the increasing survival of cancer patients [2]. Many anti-cancer drugs inhibit kinases that are critical for both cancer cell growth and cardiac homeostasis, thereby leading to the destruction of cancer cells, but also to cardiac dysfunction. The main cause of failure in early cardiotoxicity screening is the lack of relevant disease models and assay technologies that can mimic the complex conditions of the human cardiovascular system and subsequently detect cardiac side effects.We developed a combination of novel cardiotoxicity assays based on our hiPSC-derived cardiomyocytes (Pluricyte? Cardiomyocytes) to determine cardiotoxicity of (novel) pharmaceuticals. In addition to assays that can detect pro-arrhythmic effects (e.g. multi-electrode array assays), we developed functional assays to study other types of cardiotoxic effects, such as kinase activity assays and detection of alterations in contractility. For a set of oncology drugs (doxorubicin and the tyrosine kinase inhibitors sunitinib, imatinib, lapatinib and nilotinib) we investigated cardiotoxic effects in Pluricyte? Cardiomyocytes through a range of biochemistry- and electrophysiology-based assays. Treatment of the cardiomyocytes with these drugs led to the expected alterations in beating patterns, as well as in contractility and viability of the cells, supporting the use of hiPSC-derived cardiomyocytes to assess toxic effects of cardio-active compounds in preclinical research. Our multiparameter platform, which combines hiPSC-derived cardiomyocytes with biochemistry- and electrophysiology-based assays, enables early cardiotoxicity screening with the potential to greatly reduce the use of animal experiments in preclinical development.<br><br>[1] Khan et al., British Journal of Pharmacology, 2013<br>[2] Sheppard et al., Frontiers in Pharmacology, 2013<br><br><b>Disclosure</b>: The authors are employees of Pluriomics B.V., a biotech company which commercialized hiPSC-derived cardiomyocytes and assays with these cells

Intensity of mental health treatment of cancer‑related psychopathology: The predictive role of Early Maladaptive Schemas

Purpose With the limited availability of mental healthcare, it is of utmost importance to provide care that matches the needs of patients: short if possible, but also more intense when necessary. This study explored whether Early Maladaptive Schemas (EMSs) play a predictive role in the intensity of needed mental health treatment of cancer-related psychopathology. Methods EMSs were assessed before mental health treatment in 256 patients who sought help at a specialized mental health care centre for those affected by cancer in the Netherlands. Data about treatment indication and intensity of mental health treatment were collected. Univariate and multivariate logistic regression analysis were used to assess the predictive value of the EMSs total score and specific domains on treatment indication and treatment intensity. Results The presence of more severe EMSs predicted an indication for a more intense mental health treatment before start of the treatment, and actual more intense mental health treatment. The domain Impaired Autonomy and Performance appeared to be conceptually close to the domain Disconnection and Rejection, we left the latter out in our multivariate analysis and then found that Impaired Autonomy was the best predictor of intensity of mental health treatment. Conclusion Our findings imply that assessing EMSs could help to identify patients who will receive more treatment time