Moving toward precision medicine to predict drug sensitivity in patients with metastatic breast cancer.

Tumor heterogeneity represents a major challenge in breast cancer, being associated with disease progression and treatment resistance. Precision medicine has been extensively applied to dissect tumor heterogeneity and, through a deeper molecular understanding of the disease, to personalize therapeutic strategies. In the last years, technological advances have widely improved the understanding of breast cancer biology and several trials have been developed to translate these new insights into clinical practice, with the ultimate aim of improving patients' outcomes. In the era of molecular oncology, genomics analyses and other methodologies are shaping a new treatment algorithm in breast cancer care. In this manuscript, we review the main steps of precision medicine to predict drug sensitivity in breast cancer from a translational point of view. Genomic developments and their clinical implications are discussed, along with technological advancements that could broaden precision medicine applications. Current achievements are put into perspective to provide an overview of the state-of-art of breast cancer precision oncology as well as to identify future research directions.

Comparison of three approaches to model grapevine organogenesis in conditions of fluctuating temperature, solar radiation and soil water content.

BACKGROUND AND AIMS: There is increasing interest in the development of plant growth models representing the complex system of interactions between the different determinants of plant development. These approaches are particularly relevant for grapevine organogenesis, which is a highly plastic process dependent on temperature, solar radiation, soil water deficit and trophic competition. METHODS: The extent to which three plant growth models were able to deal with the observed plasticity of axis organogenesis was assessed. In the first model, axis organogenesis was dependent solely on temperature, through thermal time. In the second model, axis organogenesis was modelled through functional relationships linking meristem activity and trophic competition. In the last model, the rate of phytomer appearence on each axis was modelled as a function of both the trophic status of the plant and the direct effect of soil water content on potential meristem activity. KEY RESULTS: The model including relationships between trophic competition and meristem behaviour involved a decrease in the root mean squared error (RMSE) for the simulations of organogenesis by a factor nine compared with the thermal time-based model. Compared with the model in which axis organogenesis was driven only by trophic competition, the implementation of relationships between water deficit and meristem behaviour improved organogenesis simulation results, resulting in a three times divided RMSE. The resulting model can be seen as a first attempt to build a comprehensive complete plant growth model simulating the development of the whole plant in fluctuating conditions of temperature, solar radiation and soil water content. CONCLUSIONS: We propose a new hypothesis concerning the effects of the different determinants of axis organogenesis. The rate of phytomer appearance according to thermal time was strongly affected by the plant trophic status and soil water deficit. Furthermore, the decrease in meristem activity when soil water is depleted does not result from source/sink imbalances.

Simulation of fruit-set and trophic competition and optimization of yield advantages in six Capsicum cultivars using functional-structural plant modelling.

BACKGROUND AND AIMS: Many indeterminate plants can have wide fluctuations in the pattern of fruit-set and harvest. Fruit-set in these types of plants depends largely on the balance between source (assimilate supply) and sink strength (assimilate demand) within the plant. This study aims to evaluate the ability of functional-structural plant models to simulate different fruit-set patterns among Capsicum cultivars through source-sink relationships. METHODS: A greenhouse experiment of six Capsicum cultivars characterized with different fruit weight and fruit-set was conducted. Fruit-set patterns and potential fruit sink strength were determined through measurement. Source and sink strength of other organs were determined via the GREENLAB model, with a description of plant organ weight and dimensions according to plant topological structure established from the measured data as inputs. Parameter optimization was determined using a generalized least squares method for the entire growth cycle. KEY RESULTS AND CONCLUSIONS: Fruit sink strength differed among cultivars. Vegetative sink strength was generally lower for large-fruited cultivars than for small-fruited ones. The larger the size of the fruit, the larger variation there was in fruit-set and fruit yield. Large-fruited cultivars need a higher source-sink ratio for fruit-set, which means higher demand for assimilates. Temporal heterogeneity of fruit-set affected both number and yield of fruit. The simulation study showed that reducing heterogeneity of fruit-set was obtained by different approaches: for example, increasing source strength; decreasing vegetative sink strength, source-sink ratio for fruit-set and flower appearance rate; and harvesting individual fruits earlier before full ripeness. Simulation results showed that, when we increased source strength or decreased vegetative sink strength, fruit-set and fruit weight increased. However, no significant differences were found between large-fruited and small-fruited groups of cultivars regarding the effects of source and vegetative sink strength on fruit-set and fruit weight. When the source-sink ratio at fruit-set decreased, the number of fruit retained on the plant increased competition for assimilates with vegetative organs. Therefore, total plant and vegetative dry weights decreased, especially for large-fruited cultivars. Optimization study showed that temporal heterogeneity of fruit-set and ripening was predicted to be reduced when fruits were harvested earlier. Furthermore, there was a 20 % increase in the number of extra fruit set.

A dynamic model of plant growth with interactions between development and functional mechanisms to study plant structural plasticity related to trophic competition.

BACKGROUND AND AIMS: The strong influence of environment and functioning on plant organogenesis has been well documented by botanists but is poorly reproduced in most functional-structural models. In this context, a model of interactions is proposed between plant organogenesis and plant functional mechanisms. METHODS: The GreenLab model derived from AMAP models was used. Organogenetic rules give the plant architecture, which defines an interconnected network of organs. The plant is considered as a collection of interacting 'sinks' that compete for the allocation of photosynthates coming from 'sources'. A single variable characteristic of the balance between sources and sinks during plant growth controls different events in plant development, such as the number of branches or the fruit load. KEY RESULTS: Variations in the environmental parameters related to light and density induce changes in plant morphogenesis. Architecture appears as the dynamic result of this balance, and plant plasticity expresses itself very simply at different levels: appearance of branches and reiteration, number of organs, fructification and adaptation of ecophysiological characteristics. CONCLUSIONS: The modelling framework serves as a tool for theoretical botany to explore the emergence of specific morphological and architectural patterns and can help to understand plant phenotypic plasticity and its strategy in response to environmental changes.