Resistance to HSP90 inhibition involving loss of MCL1 addiction

YesInhibition of the chaperone heat-shock protein 90 (HSP90) induces apoptosis, and it is a promising anti-cancer strategy. The mechanisms underpinning apoptosis activation following HSP90 inhibition and how they are modified during acquired drug resistance are unknown. We show for the first time that, to induce apoptosis, HSP90 inhibition requires the cooperation of multi BH3-only proteins (BID, BIK, PUMA) and the reciprocal suppression of the pro-survival BCL-2 family member MCL1, which occurs via inhibition of STAT5A. A subset of tumour cell lines exhibit dependence on MCL1 expression for survival and this dependence is also associated with tumour response to HSP90 inhibition. In the acquired resistance setting, MCL1 suppression in response to HSP90 inhibitors is maintained; however, a switch in MCL1 dependence occurs. This can be exploited by the BH3 peptidomimetic ABT737, through non-BCL-2-dependent synthetic lethality

A Novel Classification of Lung Cancer into Molecular Subtypes

The remarkably heterogeneous nature of lung cancer has become more apparent over the last decade. In general, advanced lung cancer is an aggressive malignancy with a poor prognosis. The discovery of multiple molecular mechanisms underlying the development, progression, and prognosis of lung cancer, however, has created new opportunities for targeted therapy and improved outcome. In this paper, we define “molecular subtypes” of lung cancer based on specific actionable genetic aberrations. Each subtype is associated with molecular tests that define the subtype and drugs that may potentially treat it. We hope this paper will be a useful guide to clinicians and researchers alike by assisting in therapy decision making and acting as a platform for further study. In this new era of cancer treatment, the ‘one-size-fits-all’ paradigm is being forcibly pushed aside—allowing for more effective, personalized oncologic care to emerge

Advantages and Disadvantages of Modeling Beliefs by Single Item and Scale Models in the Context of the Theory of Planned Behavior

Teachers’ beliefs about science teaching vary greatly. To analyze the relationships between teachers’ beliefs and other variables related to teaching and learning, researchers can use the following two options: single item belief models or belief scales. In this study, we compared both models in the context of teachers’ beliefs regarding teaching about cancer. Although both models exhibited a good model fit, each approach had both advantages and disadvantages when we judged the modelling approaches in terms of fulfilling the requirements of common psychometric standards and adequately acknowledging the diversity of different beliefs. We discuss the predictive value of both models and their contribution to planning belief-based interventions for cancer education. We argue that researchers should combine the advantages of single item and scale models when analyzing the diversity of teachers’ beliefs

La autorreflexión en García de Pablo García Casado

Las estrategias autorreflexivas son muy ocurrentes en la poesía contemporánea: en el último poemario de Pablo García Casado (García Casado 2015) conducen al yo poético al conocimiento de sí mismo y de la realidad presente mediante un viaje introspectivo que, al mismo tiempo, evoca en el nivel enunciativo tres características eminentes de la poesía: ciclicidad, tradición e innovación