Claudiu-Laurentiu Josan

Cancer detection has made significant progress, moving from conventional methods to innovative, non-invasive or minimally invasive approaches aimed at improving early diagnosis, precision, and treatment outcomes. This review examines current and emerging diagnostic technologies, including liquid biopsy (LB), molecular biomarkers, and artificial intelligence (AI). LB analyzes biomarkers in bodily fluids, showing promise in detecting tumors at molecular levels, monitoring cancer progression, and predicting treatment responses. The assignment of specific proteoforms, often linked to tumor subtype, stage, and therapy resistance, adds another layer of diagnostic precision, offering valuable insights for personalized oncology. However, the clinical application of LB faces challenges related to sensitivity, specificity, tumor heterogeneity, and a lack of standardized protocols. Relatively high costs, complex result interpretation, and privacy concerns also hinder its widespread adoption in clinical practice. Despite these challenges, advancements in AI, nanotechnology, and multi-omics strategies offer opportunities to enhance cancer diagnostic accuracy. Future developments, including wearable biosensors and lab-on-a-chip technologies, could lead to personalized, real-time cancer detection with improved patient outcomes, potentially redefining cancer care and fostering a more proactive, patient-centered healthcare approach.

Environmental exposure to a mixture of chemical xenobiotics acts as a double-edged sword, promoting or suppressing tumorigenesis and the development of breast cancer (BC). Before anything else, we are what we eat. In this review, we highlight both “the good” and “the bad” sides of the daily human diet and dietary patterns that could influence BC risk (BCR) and incidence. Thus, regularly eating new, diversified, colorful, clean, nutrient-rich, energy-boosting, and raw food, increases apoptosis and autophagy, antioxidation, cell cycle arrest, anti-inflammation, and the immune response against BC cells. Moreover, a healthy diet could lead to a reduction in or the inhibition of genomic instability, BC cell stemness, growth, proliferation, invasion, migration, and distant metastasis. We also emphasize that, in addition to beneficial compounds, our food is more and more contaminated by chemicals with harmful effects, which interact with each other and with endogenous proteins and lipids, resulting in synergistic or antagonistic effects. Thus, a healthy and diverse diet, combined with appropriate nutritional behaviors, can exert anti-carcinogenic effects and improve treatment efficacy, BC patient outcomes, and the overall quality of life of BC patients.

Proteins are the most common types of biomarkers used in breast cancer (BC) theranostics and management. By definition, a biomarker must be a relevant, objective, stable, and quantifiable biomolecule or other parameter, but proteins are known to exhibit the most variate and profound structural and functional variation. Thus, the proteome is highly dynamic and permanently reshaped and readapted, according to changing microenvironments, to maintain the local cell and tissue homeostasis. It is known that protein posttranslational modifications (PTMs) can affect all aspects of protein function. In this review, we focused our analysis on the different types of PTMs of histological biomarkers in BC. Thus, we analyzed the most common PTMs, including phosphorylation, acetylation, methylation, ubiquitination, SUMOylation, neddylation, palmitoylation, myristoylation, and glycosylation/sialylation/fucosylation of transcription factors, proliferation marker Ki-67, plasma membrane proteins, and histone modifications. Most of these PTMs occur in the presence of cellular stress. We emphasized that these PTMs interfere with these biomarkers maintenance, turnover and lifespan, nuclear or subcellular localization, structure and function, stabilization or inactivation, initiation or silencing of genomic and non-genomic pathways, including transcriptional activities or signaling pathways, mitosis, proteostasis, cell–cell and cell–extracellular matrix (ECM) interactions, membrane trafficking, and PPIs. Moreover, PTMs of these biomarkers orchestrate all hallmark pathways that are dysregulated in BC, playing both pro- and/or antitumoral and context-specific roles in DNA damage, repair and genomic stability, inactivation/activation of tumor-suppressor genes and oncogenes, phenotypic plasticity, epigenetic regulation of gene expression and non-mutational reprogramming, proliferative signaling, endocytosis, cell death, dysregulated TME, invasion and metastasis, including epithelial–mesenchymal/mesenchymal–epithelial transition (EMT/MET), and resistance to therapy or reversal of multidrug therapy resistance. PTMs occur in the nucleus but also at the plasma membrane and cytoplasmic level and induce biomarker translocation with opposite effects. Analysis of protein PTMs allows for the discovery and validation of new biomarkers in BC, mainly for early diagnosis, like extracellular vesicle glycosylation, which may be considered as a potential source of circulating cancer biomarkers.