RESUMO
Precision medicine (PM) requires the delivery of individually adapted medical care based on the genetic characteristics of each patient and his/her tumor. The last decade witnessed the development of high-throughput technologies such as microarrays and next-generation sequencing which paved the way to PM in the field of oncology. While the cost of these technologies decreases, we are facing an exponential increase in the amount of data produced. Our ability to use this information in daily practice relies strongly on the availability of an efficient bioinformatics system that assists in the translation of knowledge from the bench towards molecular targeting and diagnosis. Clinical trials and routine diagnoses constitute different approaches, both requiring a strong bioinformatics environment capable of (i) warranting the integration and the traceability of data, (ii) ensuring the correct processing and analyses of genomic data, and (iii) applying well-defined and reproducible procedures for workflow management and decision-making. To address the issues, a seamless information system was developed at Institut Curie which facilitates the data integration and tracks in real-time the processing of individual samples. Moreover, computational pipelines were developed to identify reliably genomic alterations and mutations from the molecular profiles of each patient. After a rigorous quality control, a meaningful report is delivered to the clinicians and biologists for the therapeutic decision. The complete bioinformatics environment and the key points of its implementation are presented in the context of the SHIVA clinical trial, a multicentric randomized phase II trial comparing targeted therapy based on tumor molecular profiling versus conventional therapy in patients with refractory cancer. The numerous challenges faced in practice during the setting up and the conduct of this trial are discussed as an illustration of PM application.
RESUMO
The function and causes of kidnapping juveniles are little understood because individuals sustain some breeding costs to rear an unrelated offspring. Here we focus on the proximal causes of this behaviour in emperor penguins (Aptenodytes forsteri), whose failed breeders often kidnap chicks. We experimentally tested the hypothesis that kidnapping behaviour was the result of high residual levels of prolactin (PRL), a hormone involved in parental behaviour. Penguins with artificially decreased PRL levels by bromocriptine administration kidnapped chicks less often than control penguins. Within the bromocriptine treated group, kidnapping behaviour was not totally suppressed and the probability of kidnapping a chick was positively correlated to PRL levels measured before treatment. During breeding, emperor penguins have to forage in remote ice-free areas. In these birds, PRL secretion is poorly influenced by chick stimuli and has probably evolved to maintain a willingness to return to the colony after a long absence at sea. Therefore, penguins that have lost their chick during a foraging trip still maintain high residual PRL levels and this, combined with colonial breeding, probably facilitates kidnapping. We suggest that kidnapping in non-cooperative systems may result from a hormonal byproduct of a reproductive adaptation to extreme conditions.