Unraveling Biomarker Signatures in Triple-Negative Breast Cancer: A Systematic Review for Targeted Approaches.

Triple-negative breast cancer (TNBC) is one of the most aggressive subtypes of breast cancer, marked by poor outcomes and dismal prognosis. Due to the absence of targetable receptors, chemotherapy still represents the main therapeutic option. Therefore, current research is now focusing on understanding the specific molecular pathways implicated in TNBC, in order to identify novel biomarker signatures and develop targeted therapies able to improve its clinical management. With the aim of identifying novel molecular features characterizing TNBC, elucidating the mechanisms by which these molecular biomarkers are implicated in the tumor development and progression, and assessing the impact on cancerous cells following their inhibition or modulation, we conducted a literature search from the earliest works to December 2023 on PubMed, Scopus, and Web Of Science. A total of 146 studies were selected. The results obtained demonstrated that TNBC is characterized by a heterogeneous molecular profile. Several biomarkers have proven not only to be characteristic of TNBC but also to serve as potential effective therapeutic targets, holding the promise of a new era of personalized treatments able to improve its prognosis. The pre-clinical findings that have emerged from our systematic review set the stage for further investigation in forthcoming clinical trials.

The Drosophila Ret gene functions in the stomatogastric nervous system with the Maverick TGFß ligand and the Gfrl co-receptor.

The RET receptor tyrosine kinase is crucial for the development of the enteric nervous system (ENS), acting as a receptor for Glial cell line-derived neurotrophic factor (GDNF) via GFR co-receptors. Drosophila has a well-conserved RET homolog (Ret) that has been proposed to function independently of the Gfr-like co-receptor (Gfrl). We find that Ret is required for development of the stomatogastric (enteric) nervous system in both embryos and larvae, and its loss results in feeding defects. Live imaging analysis suggests that peristaltic waves are initiated but not propagated in mutant midguts. Examination of axons innervating the midgut reveals increased branching but the area covered by the branches is decreased. This phenotype can be rescued by Ret expression. Additionally, Gfrl shares the same ENS and feeding defects, suggesting that Ret and Gfrl might function together via a common ligand. We identified the TGFß family member Maverick (Mav) as a ligand for Gfrl and a Mav chromosomal deficiency displayed similar embryonic ENS defects. Our results suggest that the Ret and Gfrl families co-evolved before the separation of invertebrate and vertebrate lineages.