Multi-disciplinary shape optimization of an entry capsule integrated with custom neural network approximation and multi-delity approach

This paper describes a new integrated approach for the multi-disciplinary optimization of a entry capsule’s shape. Aerothermodynamics, Flight Mechanics and Thermal Protection System behaviour of a reference spaceship when crossing Martian atmosphere are considered, and several analytical, semi-empirical and numerical models are used. The multi-objective and multi-disciplinary optimization process implemented in Isight software environment allows finding a Pareto front of best shapes. The optimization process is integrated with a set of artificial neural networks, trained and updated by a multi-fidelity evolution control approach, to approximate the objective and constraint functions. Results obtained by means of the integrated approach with neural networks approximators are described and compared to the results obtained by a different optimization process, not using the approximators. The comparison highlights advantages and possible drawbacks of the proposed method, mainly in terms of calls to the true model and precision of the obtained Pareto front

Sensitivity to Entrectinib Associated with a Novel LMNA-NTRK1 Gene Fusion in Metastatic Colorectal Cancer

In metastatic colorectal cancer (CRC), actionable genetic lesions represent potential clinical opportunities. NTRK1, 2, and 3 gene rearrangements encode oncogenic fusions of the tropomyosin-receptor kinase (TRK) family of receptor tyrosine kinases in different tumor types. The TPM3-NTRK1 rearrangement is a recurring event in CRC that renders tumors sensitive to TRKA kinase inhibitors in preclinical models. We identified abnormal expression of the TRKA protein in tumor and liver metastases of a CRC patient refractory to standard therapy. Molecular characterization unveiled a novel LMNA-NTRK1 rearrangement within chromosome 1 with oncogenic potential, and the patient was treated with the pan-TRK inhibitor entrectinib, achieving partial response with decrease in hepatic target lesions from 6.8 and 8.2cm in longest diameter to 4.7 and 4.3cm, respectively. To our knowledge, this is the first clinical evidence of efficacy for therapeutic inhibition of TRKA in a solid tumor, illuminating a genomic-driven strategy to identify CRCs reliant on this oncogene to be clinically targeted with entrectinib