Natalie Waterman

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.

Post-translational modifications (PTMs) of proteins dynamically build the buffering and adapting interface between oncogenic mutations and environmental stressors, on the one hand, and cancer cell structure, functioning, and behavior. Aberrant PTMs can be considered as enabling characteristics of cancer as long as they orchestrate all malignant modifications and variability in the proteome of cancer cells, cancer-associated cells, and tumor microenvironment (TME). On the other hand, PTMs of proteins can enhance anticancer mechanisms in the tumoral ecosystem or sustain the beneficial effects of oncologic therapies through degradation or inactivation of carcinogenic proteins or/and activation of tumor-suppressor proteins. In this review, we summarized and analyzed a wide spectrum of PTMs of proteins involved in all regulatory mechanisms that drive tumorigenesis, genetic instability, epigenetic reprogramming, all events of the metastatic cascade, cytoskeleton and extracellular matrix (ECM) remodeling, angiogenesis, immune response, tumor-associated microbiome, and metabolism rewiring as the most important hallmarks of cancer. All cancer hallmarks develop due to PTMs of proteins, which modulate gene transcription, intracellular and extracellular signaling, protein size, activity, stability and localization, trafficking, secretion, intracellular protein degradation or half-life, and protein–protein interactions (PPIs). PTMs associated with cancer can be exploited to better understand the underlying molecular mechanisms of this heterogeneous and chameleonic disease, find new biomarkers of cancer progression and prognosis, personalize oncotherapies, and discover new targets for drug development.